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Zhu C, Li L, Zhao M, Li J, Gao H, Li H, Liu Y, Ji C, Huang Z. Risk of premature cardiovascular disease and all-cause mortality in young adults, association with risk factor prevalence early in life. BMC Cardiovasc Disord 2025; 25:352. [PMID: 40335893 PMCID: PMC12057125 DOI: 10.1186/s12872-025-04814-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 05/02/2025] [Indexed: 05/09/2025] Open
Abstract
BACKGROUND With the increase in risk factors and the emergence of unhealthy lifestyles in young adults, we need to pay more attention to the cardiovascular health of this group. This study aimed to assess the association of the degree of joint risk factor control with premature cardiovascular disease (CVD) and all-cause mortality in young people. METHODS Kailuan Study is a prospective cohort study based on a community population, which began in June 2006, and followed up every two years. A sample of 16,519 eligible participants in the Kailuan cohort was recruited in this current study and 15,948 was included in the final analysis, with an average age of 32.34 ± 5.19 years, and a male proportion of 74.76%. Based on the control status of the risk factors, participants were divided into three groups: well-controlled group (≥ 7 risk factors controlled), moderately controlled group (5-6 risk factors controlled), and poorly controlled group (≤ 4 risk factors controlled). Multivariate Cox proportional hazard model was used to analyse the relationship between the joint control of risk factors and onset of CVD and all-cause mortality. RESULTS During a mean follow-up period of 14.78 ± 1.33 years, we identified 285 incident CVD cases and a total of 274 deaths from all causes. Compared to the well-controlled group, the moderately controlled group and poorly controlled group exhibited progressively higher risks of CVD and all-cause mortality. The adjusted hazard ratios (HRs) for CVD in the moderately controlled group and poorly controlled group were 2.24 (95% confidence interval [CI]: 1.66-3.02) and 3.09 (95% CI: 2.04-4.68), respectively. The adjusted HRs for all-cause mortality in these two groups were 1.53 (1.15-2.04) and 2.65 (1.79-3.92), respectively. CONCLUSIONS We observed an inverse relationship between the degree of risk factor control and the risk of CVD and all-cause mortality in young adults, emphasizing the importance of actively controlling more risk factors in early life.
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Affiliation(s)
- Chenrui Zhu
- Department of Cardiology, Kailuan General Hospital, 57 Xinhua East Road, Tangshan, 063000, China
| | - Liuxin Li
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Shenyang, China
| | - Mingchen Zhao
- Department of Cardiology, Kailuan General Hospital, 57 Xinhua East Road, Tangshan, 063000, China
| | - Jie Li
- Department of General Practice, Kailuan General Hospital, 57 Xinhua East Road, Tangshan, 063000, China
| | - Haibo Gao
- Department of Cardiology, The Affiliated Hospital of North China University of Science and Technology, Tangshan, 063000, China
| | - Huiying Li
- Department of Cardiology, Kailuan General Hospital, 57 Xinhua East Road, Tangshan, 063000, China
| | - Yan Liu
- Department of Cardiology, Kailuan General Hospital, 57 Xinhua East Road, Tangshan, 063000, China
| | - Chunpeng Ji
- Department of Cardiology, Kailuan General Hospital, 57 Xinhua East Road, Tangshan, 063000, China
| | - Zhe Huang
- Department of Cardiology, Kailuan General Hospital, 57 Xinhua East Road, Tangshan, 063000, China.
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Puig-Jové C, Viñals C, Conget I, Quirós C, Vinagre I, Berrocal B, Blanco-Carrasco AJ, Granados M, Mesa A, Serés-Noriega T, Giménez M, Perea V, Amor AJ. Association between the GMI/HbA1c ratio and preclinical carotid atherosclerosis in type 1 diabetes: impact of the fast-glycator phenotype across age groups. Cardiovasc Diabetol 2025; 24:75. [PMID: 39953520 PMCID: PMC11829493 DOI: 10.1186/s12933-025-02637-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 02/06/2025] [Indexed: 02/17/2025] Open
Abstract
BACKGROUND Since the arrival of continuous glucose monitoring (CGM), the relationship between the glucose management indicator (GMI) and HbA1c has been a topic of considerable interest in diabetes research. This study aims to explore the association between the GMI/HbA1c ratio and the presence of preclinical carotid atherosclerosis in type 1 diabetes (T1D). METHODS Individuals with T1D and no prior history of cardiovascular disease were recruited from two centers. Carotid ultrasonography was performed using a standardized protocol and carotid plaques were defined as intima-media thickness ≥ 1.5 mm. CGM-derived data were collected from a 14-day report. A GMI/HbA1c ratio < 0.90 was selected to identify "fast-glycator" phenotype. RESULTS A total of 584 participants were included (319 women, 54.6%), with a mean age of 48.8 ± 10.7 years and a mean diabetes duration of 27.5 ± 11.4 years. Carotid plaques were present in 231 subjects (39.6%). Approximately 43.7% and 13.4% of participants showed absolute differences of ≥ 0.5 and ≥ 1.0 between 14-day GMI and HbA1c, respectively. Among patients ≥ 48 years, the fast-glycator phenotype was independently associated with presence of plaques (OR 2.27, 95%CI: 1.06-4.87), even after adjusting for non-specific and T1D-specific risk factors and statin treatment. No significant association was observed in younger subjects (p for interaction < 0.05). CONCLUSIONS Fast-glycator phenotype is independently associated with atherosclerosis in T1D individuals aged ≥ 48 years, suggesting an age-related increase in the glycation risk. These findings highlight the potential of the GMI/HbA1c ratio for cardiovascular risk stratification in this population.
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Affiliation(s)
- Carlos Puig-Jové
- Endocrinology and Nutrition Department, Hospital Universitari Mútua Terrassa, Dr Robert 5, 08221, Barcelona, Spain
| | - Clara Viñals
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic de Barcelona, Villarroel 170, 08036, Barcelona, Spain
- Fundació Clínic per a la Recerca Biomèdica (FCRB)-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain
| | - Ignacio Conget
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic de Barcelona, Villarroel 170, 08036, Barcelona, Spain
- Fundació Clínic per a la Recerca Biomèdica (FCRB)-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain
| | - Carmen Quirós
- Endocrinology and Nutrition Department, Hospital Universitari Mútua Terrassa, Dr Robert 5, 08221, Barcelona, Spain
| | - Irene Vinagre
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic de Barcelona, Villarroel 170, 08036, Barcelona, Spain
- Fundació Clínic per a la Recerca Biomèdica (FCRB)-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain
| | - Belén Berrocal
- Endocrinology and Nutrition Department, Hospital Universitari Mútua Terrassa, Dr Robert 5, 08221, Barcelona, Spain
| | - Antonio-Jesús Blanco-Carrasco
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic de Barcelona, Villarroel 170, 08036, Barcelona, Spain
- Fundació Clínic per a la Recerca Biomèdica (FCRB)-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain
| | - Montserrat Granados
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic de Barcelona, Villarroel 170, 08036, Barcelona, Spain
| | - Alex Mesa
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic de Barcelona, Villarroel 170, 08036, Barcelona, Spain
- Endocrinology and Nutrition Department, Hospital de la Santa Creu i Sant Pau, 08041, Barcelona, Spain
| | - Tonet Serés-Noriega
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic de Barcelona, Villarroel 170, 08036, Barcelona, Spain
| | - Marga Giménez
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic de Barcelona, Villarroel 170, 08036, Barcelona, Spain
- Fundació Clínic per a la Recerca Biomèdica (FCRB)-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain
| | - Verónica Perea
- Endocrinology and Nutrition Department, Hospital Universitari Mútua Terrassa, Dr Robert 5, 08221, Barcelona, Spain.
| | - Antonio J Amor
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic de Barcelona, Villarroel 170, 08036, Barcelona, Spain.
- Fundació Clínic per a la Recerca Biomèdica (FCRB)-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain.
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Tomic D, Harding JL, Jenkins AJ, Shaw JE, Magliano DJ. The epidemiology of type 1 diabetes mellitus in older adults. Nat Rev Endocrinol 2025; 21:92-104. [PMID: 39448829 DOI: 10.1038/s41574-024-01046-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/26/2024] [Indexed: 10/26/2024]
Abstract
Although type 1 diabetes mellitus (T1DM) is traditionally viewed as a youth-onset disorder, the number of older adults being diagnosed with this disease is growing. Improvements in the average life expectancy of people with T1DM have also contributed to the growing number of older people living with this disease. We summarize the evidence regarding the epidemiology (incidence, prevalence and excess mortality) of T1DM in older adults (ages ≥60 years) as well as the genetics, immunology and diagnostic challenges. Several studies report an incidence peak of T1DM in older adults of a similar size to or exceeding that in children, and population prevalence generally increases with increasing age. Glutamic acid decarboxylase antibody positivity is frequently observed in adult-onset T1DM. Guidelines for differentiating T1DM from type 2 diabetes mellitus in older adults recommend measuring levels of C-peptide and autoantibodies, including glutamic acid decarboxylase antibodies. However, there is no gold standard for differentiating T1DM from type 2 diabetes mellitus in people aged 60 years and over. As such, the global variation observed in T1DM epidemiology might be in part explained by misclassification, which increases with increasing age of diabetes mellitus onset. With a growing global population of older adults with T1DM, improved genetic and immunological evidence is needed to differentiate diabetes mellitus type at older ages so that a clear epidemiological picture can emerge.
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Affiliation(s)
- Dunya Tomic
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
| | - Jessica L Harding
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Alicia J Jenkins
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- Faculty of Medicine, Monash University, Melbourne, Victoria, Australia
- Baker Department of Cardiometabolic Health, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia
| | - Jonathan E Shaw
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
| | - Dianna J Magliano
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
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Armentrout BL, Ahmed BH, Waraphok S, Huynh J, Griggs S. Emotional Distress and Cardiovascular Health in Young Adults with Type 1 Diabetes. J Cardiovasc Dev Dis 2024; 11:391. [PMID: 39728281 DOI: 10.3390/jcdd11120391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 11/29/2024] [Accepted: 12/03/2024] [Indexed: 12/28/2024] Open
Abstract
Type 1 diabetes (T1D) is a complex chronic condition that places young adults aged 18-31 years at high risk for general and diabetes-related distress and poor cardiovascular health. Both general and diabetes distress are linked to higher A1C, a known risk factor for cardiovascular disease (CVD). The purpose of this cross-sectional quantitative descriptive study was to examine the associations between distress symptoms (general and diabetes) and cardiovascular health while considering covariates in young adults ages 18-31 years with T1D. One-hundred and sixty-five young adults with T1D, recruited from specialty clinics through two major health systems and online platforms, completed a demographic and clinical survey along with the 8-item PROMIS Emotional Distress Scale and 17-item Diabetes Distress Scale. Higher diabetes distress and higher general emotional distress were associated with lower cardiovascular health scores. Associations remained statistically significant after adjusting for age, T1D duration, sex at birth, race, and continuous subcutaneous insulin infusion. In young adults with type 1 diabetes, addressing both diabetes and general emotional distress may be important to improve cardiovascular health. However, longitudinal and experimental studies are needed to clarify underlying mechanisms and evaluate the effectiveness of interventions like cognitive behavioral therapy.
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Affiliation(s)
- Bethany L Armentrout
- Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Bootan H Ahmed
- Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Sineenat Waraphok
- Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Johnathan Huynh
- Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Stephanie Griggs
- Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH 44106, USA
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Kryst J, Matejko B, Czerwińska-Ledwig O, Tota Ł, Zuziak R, Piotrowska A. Effects of Acute Maximum-Intensity Exercise on Matrix Metalloproteinase-2, -9, and Tissue Inhibitor of Metalloproteinase-1 Levels in Adult Males with Type 1 Diabetes Mellitus Treated with Insulin Pumps. J Clin Med 2024; 13:7077. [PMID: 39685536 PMCID: PMC11641960 DOI: 10.3390/jcm13237077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 11/17/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024] Open
Abstract
Background: Dysregulation of matrix metalloproteinases (MMPs) activity is considered one of the potential causes of vascular complications in diabetic patients. Since training volume may influence MMPs levels in varying ways, the aim of our study was to evaluate changes in MMPs levels following acute maximum-intensity exercise in male patients with type 1 diabetes mellitus (T1DM). Methods: This study included 24 male T1DM patients and 10 healthy controls. Aerobic capacity was evaluated with a treadmill test. Levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured both before the aerobic capacity test and 60 min after its completion utilizing enzyme-linked immunosorbent assay (ELISA) system kits. Results: Before the aerobic capacity test only, MMP-9 serum levels were significantly elevated in the T1DM group compared to the controls. Following maximum-intensity exercise, the levels of MMP-2, MMP-9, and TIMP-1 were significantly higher in T1DM patients than in the control group. Between-group comparisons revealed that maximum-intensity exercise induced a statistically significant increase in MMP-2 serum levels from baseline in T1DM patients compared to controls. Conclusions: Our findings suggest that high-intensity exercise in T1DM patients leads to dysregulation of MMPs, as manifested by a significant increase in MMP-2 levels. This dysregulation may play a role in the development of vascular complications in diabetic patients.
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Affiliation(s)
- Joanna Kryst
- Department of Chemistry and Biochemistry, Institute for Basics Sciences, Faculty of Physiotherapy, University of Physical Education in Kraków, 31-571 Kraków, Poland; (O.C.-L.); (R.Z.); (A.P.)
| | - Bartłomiej Matejko
- Department of Metabolic Diseases, Jagiellonian University Medical College, 30-688 Kraków, Poland;
- Metabolic Diseases and Diabetology Clinical Department, University Hospital in Krakow, 30-688 Kraków, Poland
| | - Olga Czerwińska-Ledwig
- Department of Chemistry and Biochemistry, Institute for Basics Sciences, Faculty of Physiotherapy, University of Physical Education in Kraków, 31-571 Kraków, Poland; (O.C.-L.); (R.Z.); (A.P.)
| | - Łukasz Tota
- Department of Physiology and Biochemistry, Faculty of Physical Education and Sport, University of Physical Education in Kraków, 31-571 Kraków, Poland;
| | - Roxana Zuziak
- Department of Chemistry and Biochemistry, Institute for Basics Sciences, Faculty of Physiotherapy, University of Physical Education in Kraków, 31-571 Kraków, Poland; (O.C.-L.); (R.Z.); (A.P.)
| | - Anna Piotrowska
- Department of Chemistry and Biochemistry, Institute for Basics Sciences, Faculty of Physiotherapy, University of Physical Education in Kraków, 31-571 Kraków, Poland; (O.C.-L.); (R.Z.); (A.P.)
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Zhao J, Li W, Chen L, Li M, Deng W. Casual effects of type 1 diabetes mellitus on site-specific digestive cancers: a Mendelian randomisation analysis. Front Endocrinol (Lausanne) 2024; 15:1407329. [PMID: 39301314 PMCID: PMC11410686 DOI: 10.3389/fendo.2024.1407329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 07/17/2024] [Indexed: 09/22/2024] Open
Abstract
Objective Despite several observational studies attempting to investigate the potential association between type 1 diabetes mellitus (T1DM) and the risk of digestive cancers, the results remain controversial. The purpose of this study is to examine whether there is a causal relationship between T1DM and the risk of digestive cancers. Methods We conducted a Mendelian randomisation (MR) study to systematically investigate the effect of T1DM on six most prevalent types of digestive cancers (oesophageal cancer, stomach cancer, hepatocellular carcinoma, biliary tract cancer, pancreatic cancer, and colorectal cancer). A total of 1,588,872 individuals were enrolled in this analysis, with 372,756 being the highest number for oesophageal cancer and 3,835 being the lowest for pancreatic cancer. Multiple MR methods were performed to evaluate the causal association of T1DM with the risk of six site-specific cancers using genome-wide association study summary data. Sensitivity analyses were also conducted to assess the robustness of the observed associations. Results We selected 35 single nucleotide polymorphisms associated with T1DM as instrumental variables. Our findings indicate no significant effect of T1DM on the overall risk of oesophageal cancer (OR= 0.99992, 95% CI: 0.99979-1.00006, P= 0.2866), stomach cancer (OR=0.9298,95% CI: 0.92065-1.09466, P= 0.9298), hepatocellular carcinoma (OR= 0.99994,95% CI: 0.99987-1.00001, P= 0.1125), biliary tract cancer (OR=0.97348,95% CI: 0.8079-1.1729, P= 0.7775)), or pancreatic cancer (OR =1.01258, 95% CI: 0.96243-1.06533, P= 0.6294). However, we observed a causal association between T1DM and colorectal cancer (OR=1.000, 95% CI: 1.00045-1.0012, P<0.001), indicating that T1DM increases the risk of colorectal cancer. We also performed sensitivity analyses, which showed no heterogeneity or horizontal pleiotropy. For the reverse MR from T1DM to six digestive cancers, no significant causal relationships were identified. Conclusions In this MR study with a large number of digestive cancer cases, we found no evidence to support the causal role of T1DM in the risk of oesophageal cancer, stomach cancer, hepatocellular carcinoma, biliary tract cancer, or pancreatic cancer. However, we found a causal positive association between T1DM and colorectal cancer. Further large-scale prospective studies are necessary to replicate our findings.
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Affiliation(s)
- Jinli Zhao
- Department of Emergency Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Wenjin Li
- Department of Nutrition, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Libo Chen
- Department of Urology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Mingyong Li
- Department of Urology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Weiming Deng
- Department of Urology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
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Cosmin Stan M, Paul D. Diabetes and Cancer: A Twisted Bond. Oncol Rev 2024; 18:1354549. [PMID: 38835644 PMCID: PMC11148650 DOI: 10.3389/or.2024.1354549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 04/08/2024] [Indexed: 06/06/2024] Open
Abstract
This paper presents an overview of the interconnection between various factors related to both cancer and type 2 diabetes mellitus (T2DM). Hyperglycemia, hyperinsulinemia, chronic inflammation, and obesity are involved in the development and progression of both diseases but, strong evidence for a direct causal relationship between diabetes and cancer, is lacking. Several studies described a relationship between hyperglycemia and cancer at the cellular, tissular and organismic levels but at the same time recent Mendelian randomization studies proved a significant causal relationship only between hyperglycemia and breast cancer. On the other hand, the association between both hyperinsulinemia and obesity and several cancer types appears to be robust as demonstrated by Mendelian randomized studies. Metabolic alterations, including the Warburg effect and excessive glucose consumption by tumors, are discussed, highlighting the potential impact of dietary restrictions, such as fasting and low-carb diets, on tumor growth and inflammation. Recent data indicates that circulating branched-chain amino acids levels, may represent novel biomarkers that may contribute to both better diabetes control and early pancreatic cancer detection. Understanding the underlying mechanisms and shared risk factors between cancer and T2DM can provide valuable insights for cancer prevention, early detection, and management strategies.
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Affiliation(s)
- Mihai Cosmin Stan
- Emergency County Hospital Rm. Vâlcea, Râmnicu Vâlcea, Romania
- Medical Oncology Department, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Doru Paul
- Weill Cornell Medicine, New York, NY, United States
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Lain SJ, Stevens L, Craig ME, Jenkins AJ, Bell KJ, Pryke A, Donaghue KC, Nassar N. Excess Mortality in an Inception Cohort of Childhood Diabetes Diagnosed 1990-2010. Pediatr Diabetes 2024; 2024:1844752. [PMID: 40302973 PMCID: PMC12016878 DOI: 10.1155/2024/1844752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 02/11/2024] [Accepted: 02/27/2024] [Indexed: 05/02/2025] Open
Abstract
Objective Evaluate the mortality risk of childhood-onset type 1 diabetes compared to the general population. Research Design and Methods. The study population, identified from the Australasian Paediatric Endocrinology Group diabetes register, was diagnosed with type 1 diabetes at age < 16 in New South Wales (NSW), Australia, from 1990 to 2010. The register was linked to National Death Index registrations to ascertain timing and cause of death up to 31/12/2022. Risk factors for mortality were assessed using multivariable Cox regression models and observed mortality rate compared to "expected" rates in the Australian general population using indirect-standardized mortality ratios (SMR), overall and by sex and age at diagnosis. Diabetes-related cause of death categories were identified. Results Of 5,417 children diagnosed with type 1 diabetes, 157 subsequently died, with all-cause mortality of 1.37/1,000 person years. Increased mortality risk was associated with living in most disadvantaged areas (aHR 1.81 (1.05, 3.11)) but not living in a rural area. Overall SMR was 2.83 (95% CI 2.40, 3.33) with females having higher SMR than males (4.18 vs. 2.19). Most common causes of death recorded were acute diabetes complications (26%), including diabetes ketoacidosis, accident/misadventure (21%), and chronic diabetes complications (15%). Alcohol and/or drug use contributed to 17% of deaths. Conclusion Compared to the general population, higher risk of mortality in people with type 1 diabetes was associated with female sex and living in area of socioeconomic disadvantage. Education about minimizing risk-taking behaviors should be communicated to young adults with type 1 diabetes.
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Affiliation(s)
- Samantha J. Lain
- Children's Hospital at Westmead Clinical School, The University of Sydney, Sydney, Australia
| | - Lindsay Stevens
- Children's Hospital at Westmead Clinical School, The University of Sydney, Sydney, Australia
| | - Maria E. Craig
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, Australia
- Discipline of Child and Adolescent Health, University of Sydney, Sydney, Australia
- Discipline of Paediatrics and Child Health, School of Clinical Medicine, UNSW Health, University of New South Wales, Sydney, Australia
- Charles Perkins Centre, University of Sydney, Sydney, Australia
| | | | | | - Alison Pryke
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, Australia
| | - Kim C. Donaghue
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, Australia
- Discipline of Child and Adolescent Health, University of Sydney, Sydney, Australia
| | - Natasha Nassar
- Children's Hospital at Westmead Clinical School, The University of Sydney, Sydney, Australia
- Charles Perkins Centre, University of Sydney, Sydney, Australia
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Lai SWT, Bhattacharya S, Lopez Gonzalez EDJ, Shuck SC. Methylglyoxal-Derived Nucleoside Adducts Drive Vascular Dysfunction in a RAGE-Dependent Manner. Antioxidants (Basel) 2024; 13:85. [PMID: 38247509 PMCID: PMC10812505 DOI: 10.3390/antiox13010085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 12/29/2023] [Accepted: 01/04/2024] [Indexed: 01/23/2024] Open
Abstract
Diabetic kidney disease (DKD) is a leading cause of death in patients with diabetes. An early precursor to DKD is endothelial cell dysfunction (ECD), which often precedes and exacerbates vascular disease progression. We previously discovered that covalent adducts formed on DNA, RNA, and proteins by the reactive metabolic by-product methylglyoxal (MG) predict DKD risk in patients with type 1 diabetes up to 16 years pre-diagnosis. However, the mechanisms by which MG adducts contribute to vascular disease onset and progression remain unclear. Here, we report that the most predominant MG-induced nucleoside adducts, N2-(1-carboxyethyl)-deoxyguanosine (CEdG) and N2-(1-carboxyethyl)-guanosine (CEG), drive endothelial dysfunction. Following CEdG or CEG exposure, primary human umbilical vein endothelial cells (HUVECs) undergo endothelial dysfunction, resulting in enhanced monocyte adhesion, increased reactive oxygen species production, endothelial permeability, impaired endothelial homeostasis, and exhibit a dysfunctional transcriptomic signature. These effects were discovered to be mediated through the receptor for advanced glycation end products (RAGE), as an inhibitor for intracellular RAGE signaling diminished these dysfunctional phenotypes. Therefore, we found that not only are MG adducts biomarkers for DKD, but that they may also have a role as potential drivers of vascular disease onset and progression and a new therapeutic modality.
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Affiliation(s)
- Seigmund Wai Tsuen Lai
- Department of Diabetes and Cancer Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA; (S.W.T.L.); (E.D.J.L.G.)
| | - Supriyo Bhattacharya
- Department of Computational and Quantitative Medicine, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA;
| | - Edwin De Jesus Lopez Gonzalez
- Department of Diabetes and Cancer Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA; (S.W.T.L.); (E.D.J.L.G.)
| | - Sarah C. Shuck
- Department of Diabetes and Cancer Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA; (S.W.T.L.); (E.D.J.L.G.)
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Caldara R, Tomajer V, Monti P, Sordi V, Citro A, Chimienti R, Gremizzi C, Catarinella D, Tentori S, Paloschi V, Melzi R, Mercalli A, Nano R, Magistretti P, Partelli S, Piemonti L. Allo Beta Cell transplantation: specific features, unanswered questions, and immunological challenge. Front Immunol 2023; 14:1323439. [PMID: 38077372 PMCID: PMC10701551 DOI: 10.3389/fimmu.2023.1323439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 11/06/2023] [Indexed: 12/18/2023] Open
Abstract
Type 1 diabetes (T1D) presents a persistent medical challenge, demanding innovative strategies for sustained glycemic control and enhanced patient well-being. Beta cells are specialized cells in the pancreas that produce insulin, a hormone that regulates blood sugar levels. When beta cells are damaged or destroyed, insulin production decreases, which leads to T1D. Allo Beta Cell Transplantation has emerged as a promising therapeutic avenue, with the goal of reinstating glucose regulation and insulin production in T1D patients. However, the path to success in this approach is fraught with complex immunological hurdles that demand rigorous exploration and resolution for enduring therapeutic efficacy. This exploration focuses on the distinct immunological characteristics inherent to Allo Beta Cell Transplantation. An understanding of these unique challenges is pivotal for the development of effective therapeutic interventions. The critical role of glucose regulation and insulin in immune activation is emphasized, with an emphasis on the intricate interplay between beta cells and immune cells. The transplantation site, particularly the liver, is examined in depth, highlighting its relevance in the context of complex immunological issues. Scrutiny extends to recipient and donor matching, including the utilization of multiple islet donors, while also considering the potential risk of autoimmune recurrence. Moreover, unanswered questions and persistent gaps in knowledge within the field are identified. These include the absence of robust evidence supporting immunosuppression treatments, the need for reliable methods to assess rejection and treatment protocols, the lack of validated biomarkers for monitoring beta cell loss, and the imperative need for improved beta cell imaging techniques. In addition, attention is drawn to emerging directions and transformative strategies in the field. This encompasses alternative immunosuppressive regimens and calcineurin-free immunoprotocols, as well as a reevaluation of induction therapy and recipient preconditioning methods. Innovative approaches targeting autoimmune recurrence, such as CAR Tregs and TCR Tregs, are explored, along with the potential of stem stealth cells, tissue engineering, and encapsulation to overcome the risk of graft rejection. In summary, this review provides a comprehensive overview of the inherent immunological obstacles associated with Allo Beta Cell Transplantation. It offers valuable insights into emerging strategies and directions that hold great promise for advancing the field and ultimately improving outcomes for individuals living with diabetes.
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Affiliation(s)
- Rossana Caldara
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Valentina Tomajer
- Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Paolo Monti
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Valeria Sordi
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Antonio Citro
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Raniero Chimienti
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
- Università Vita-Salute San Raffaele, Milan, Italy
| | - Chiara Gremizzi
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Davide Catarinella
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Stefano Tentori
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Vera Paloschi
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Raffella Melzi
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Alessia Mercalli
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Rita Nano
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Paola Magistretti
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Stefano Partelli
- Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy
- Università Vita-Salute San Raffaele, Milan, Italy
| | - Lorenzo Piemonti
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
- Università Vita-Salute San Raffaele, Milan, Italy
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11
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Yoo J, Jeon J, Baek M, Song SO, Kim J. Impact of statin treatment on cardiovascular risk in patients with type 1 diabetes: a population-based cohort study. J Transl Med 2023; 21:806. [PMID: 37951886 PMCID: PMC10640735 DOI: 10.1186/s12967-023-04691-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 11/02/2023] [Indexed: 11/14/2023] Open
Abstract
BACKGROUND Cardiovascular disease (CVD) is a major complication in type 1 diabetes mellitus (T1D) patients. Previous studies have suggested that statins may be helpful for prevention of CVD in T1D, but there are limited data on the role of statins in T1D. We investigated the relationship between statin treatment and cardiovascular risk in T1D patients using a population-based cohort. METHODS We conducted a retrospective cohort study using the Korean nationwide health insurance database from January 2007 to December 2017. This study included 11,009 T1D patients aged ≥ 20 years without a prior history of CVD. The primary outcome was a composite development of stroke or myocardial infarction. Statin use during follow-up was treated as a time-varying variable. We performed a multivariable time-dependent Cox regression analysis adjusting for sex, age, type of insurance, hypertension, renal disease, and use of antiplatelets and renin-angiotensin-aldosterone system inhibitors. RESULTS During the mean follow-up of 9.9 ± 3.7 years of follow-up, 931 T1D patients (8.5%) suffered primary outcome. Statin treatment was associated with a reduced risk of the primary outcome (adjusted hazard ratio, 0.76; 95% confidence interval 0.66-0.88; p < 0.001). Statin use led to decreased risks of ischemic stroke and myocardial infarction, but was not related to hemorrhagic stroke. We also found that the risk of cardiovascular events decreased as the cumulative exposure duration of statins increased. CONCLUSIONS Statin use was associated with a lower risk of cardiovascular events in T1D patients. Further prospective studies are needed to confirm the potential role of statins in prevention of CVD in patients with T1D.
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Affiliation(s)
- Joonsang Yoo
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 16995, Republic of Korea
| | - Jimin Jeon
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 16995, Republic of Korea
| | - Minyoul Baek
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 16995, Republic of Korea
| | - Sun Ok Song
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, 100 Ilsan-ro, Ilsandong-gu, Goyang, 10444, Republic of Korea.
| | - Jinkwon Kim
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 16995, Republic of Korea.
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12
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Dei Cas A, Aldigeri R, Mantovani A, Masulli M, Palmisano L, Cavalot F, Bonomo K, Baroni MG, Cossu E, Cavallo G, Cimini FA, Buzzetti R, Mignogna C, Leonetti F, Bacci S, Trevisan R, Morieri ML, Pollis RM, Targher G, Vigili de Kreutzenberg S. Sex Differences in Cardiovascular Disease and Cardiovascular Risk Estimation in Patients With Type 1 Diabetes. J Clin Endocrinol Metab 2023; 108:e789-e798. [PMID: 36881927 DOI: 10.1210/clinem/dgad127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 02/27/2023] [Accepted: 03/01/2023] [Indexed: 03/09/2023]
Abstract
CONTEXT Patients with type 1 diabetes (T1D) have higher cardiovascular disease (CVD) risk than the general population. OBJECTIVE This observational study aims to evaluate sex-related differences in CVD prevalence and CVD risk estimates in a large cohort of T1D adults. METHODS We conducted a multicenter, cross-sectional study involving 2041 patients with T1D (mean age 46 years; 44.9% women). In patients without pre-existing CVD (primary prevention), we used the Steno type 1 risk engine to estimate the 10-year risk of developing CVD events. RESULTS CVD prevalence (n = 116) was higher in men than in women aged ≥55 years (19.2 vs 12.8%, P = .036), but comparable between the 2 sexes in those aged <55 years (P = .91). In patients without pre-existing CVD (n = 1925), mean 10-year estimated CVD risk was 15.4 ± 0.4% without any significant sex difference. However, stratifying this patient group by age, the 10-year estimated CVD risk was significantly higher in men than in women until age 55 years (P < .001), but this risk equalized after this age. Carotid artery plaque burden was significantly associated with age ≥55 years and with a medium and high 10-year estimated CVD risk, without any significant sex difference. Diabetic retinopathy and sensory-motor neuropathy were also associated with higher 10-year CVD risk and female sex. CONCLUSION Both men and women with T1D are at high CVD risk. The 10-year estimated CVD risk was higher in men aged <55 years than in women of similar age, but these sex differences disappeared at age ≥55 years, suggesting that female sex was no longer protective.
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Affiliation(s)
- Alessandra Dei Cas
- Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
- Division of Nutritional and Metabolic Sciences, Azienda Ospedaliero-Universitaria di Parma, 43126 Parma, Italy
| | - Raffaella Aldigeri
- Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, 37124 Verona, Italy
| | - Maria Masulli
- Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy
| | - Luisa Palmisano
- Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy
| | - Franco Cavalot
- Diabetes and Metabolic Diseases Unit, San Luigi Gonzaga University Hospital, 10043 Turin, Italy
| | - Katia Bonomo
- Diabetes and Metabolic Diseases Unit, San Luigi Gonzaga University Hospital, 10043 Turin, Italy
| | - Marco Giorgio Baroni
- Department of Clinical Medicine, Life, Health & Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy
- Neuroendocrinology and Metabolic Diseases, IRCCS Neuromed, 86077 Pozzilli, Italy
| | - Efisio Cossu
- Unit of Diabetology, Policlinico Universitario of Cagliari, 09124 Cagliari, Italy
| | - Gisella Cavallo
- Department of Experimental Medicine, Sapienza University, 00185 Rome, Italy
| | | | - Raffaella Buzzetti
- Department of Experimental Medicine, Sapienza University, 00185 Rome, Italy
| | - Carmen Mignogna
- Department of Experimental Medicine, Sapienza University, 00185 Rome, Italy
| | - Frida Leonetti
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University, 00185 Rome, Italy
| | - Simonetta Bacci
- Section of Endocrinology, Department of Medicine, IRCCS, Casa Sollievo della Sofferenza Hospital, 71013 San Giovanni Rotondo (FG), Italy
| | - Roberto Trevisan
- Department of Medicine and Surgery, University of Milan Bicocca, 20126 Milan, Italy
| | - Mario Luca Morieri
- Metabolic Diseases, Department of Medicine, University of Padua, 35128 Padua, Italy
| | | | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, 37124 Verona, Italy
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13
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Giménez-Pérez G, Viñals C, Mata-Cases M, Vlacho B, Real J, Franch-Nadal J, Ortega E, Mauricio D. Epidemiology of the first-ever cardiovascular event in people with type 1 diabetes: a retrospective cohort population-based study in Catalonia. Cardiovasc Diabetol 2023; 22:179. [PMID: 37452416 PMCID: PMC10349453 DOI: 10.1186/s12933-023-01917-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 07/04/2023] [Indexed: 07/18/2023] Open
Abstract
BACKGROUND Knowledge of the characteristics of first-ever cardiovascular events in type 1 diabetes may impact primary prevention strategies. This study describes the first-ever manifestation of cardiovascular disease (CVD) in patients with type 1 diabetes (T1D) in Catalonia (Spain) and evaluates differences according to age and sex. METHODS Retrospective cohort study of patients with T1D > 30 years without CVD before 2010 registered in the SIDIAP database. The occurrence of a first cardiovascular event up to the end of 2016, the type of CV event and associations with baseline characteristics were analysed. RESULTS Of 8412 patients, 884 suffered a first CV event (incidence rate 1.62 per 100 persons-years). Overall, peripheral vascular disease (39.5%) was the most frequent event. We observed a higher proportion of heart failure in women (21.7%) than in men (10.1%). In women, heart failure was the most frequent event in those > 65 years (40.5%). Decreased glomerular filtration rate (hazard ratio [HR] 5.42 [95% CI 4.32;6.80]), elevated albumin/creatinine ratio (HR 3.39 [95% CI [2.47;4.66], microvascular complications (HR 3.27 [95% CI 2.85;3.75]), and hypertension (HR 3.21 [95% CI [2.80;3.67]) were most strongly associated with a first CV event. HbA1c > 7.0% was associated with incident CVD only in patients aged < 55/60 years. CONCLUSIONS Peripheral artery disease in the whole cohort, and heart failure in elder subjects are the most frequent first-ever CVD events in T1D in our region. These findings deserve to be taken into account when considering primary prevention measures and when estimating CV risk in people with T1D.
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Affiliation(s)
- Gabriel Giménez-Pérez
- Section of Endocrinology, Department of Medicine, Hospital General de Granollers, Granollers, Spain
- School of Medicine and Health Sciences, Universitat Internacional de Catalunya, Sant Cugat del Vallès, Spain
| | - Clara Viñals
- Department of Endocrinology & Nutrition, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Manel Mata-Cases
- DAP-Cat Group, Unitat de Suport a La Recerca Barcelona Ciutat, Institut Universitari d’Investigació en Atenció Primària Jordi Gol, Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain
- Primary Health Care Center La Mina, Gerència d’Àmbit d’Atenció Primària Barcelona Ciutat, Institut Català de La Salut, Sant Adrià de Besòs, Spain
| | - Bogdan Vlacho
- DAP-Cat Group, Unitat de Suport a La Recerca Barcelona Ciutat, Institut Universitari d’Investigació en Atenció Primària Jordi Gol, Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain
| | - Jordi Real
- DAP-Cat Group, Unitat de Suport a La Recerca Barcelona Ciutat, Institut Universitari d’Investigació en Atenció Primària Jordi Gol, Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain
| | - Josep Franch-Nadal
- DAP-Cat Group, Unitat de Suport a La Recerca Barcelona Ciutat, Institut Universitari d’Investigació en Atenció Primària Jordi Gol, Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain
- Primary Health Care Center Raval Sud, Gerència d’Àmbit d’Atenció Primària Barcelona Ciutat, Institut Català de La Salut, Barcelona, Spain
| | - Emilio Ortega
- Department of Endocrinology & Nutrition, Hospital Clínic de Barcelona, Barcelona, Spain
- DAP-Cat Group, Unitat de Suport a La Recerca Barcelona Ciutat, Institut Universitari d’Investigació en Atenció Primària Jordi Gol, Barcelona, Spain
- CIBER of Physiopathology of Obesity and Nutrition, ISCIII, Madrid, Spain
| | - Dídac Mauricio
- DAP-Cat Group, Unitat de Suport a La Recerca Barcelona Ciutat, Institut Universitari d’Investigació en Atenció Primària Jordi Gol, Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain
- Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Department of Medicine, University of Vic - Central University of Catalonia, Vic, Spain
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14
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Jahn LA, Hartline LM, Kleiner AJ, Horton WB, Hasan F, Wai Kit Tan A, Liu Z, Barrett EJ. Insulin-induced vasoconstriction is prevalent in muscle microvasculature of otherwise healthy persons with type 1 diabetes. Am J Physiol Endocrinol Metab 2023; 324:E402-E408. [PMID: 36920998 PMCID: PMC10125023 DOI: 10.1152/ajpendo.00242.2022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 02/09/2023] [Accepted: 03/09/2023] [Indexed: 03/16/2023]
Abstract
Insulin's microvascular actions and their relationship to insulin's metabolic actions have not been well studied in adults with type 1 diabetes mellitus (T1DM). We compared the metabolic and selected micro- and macrovascular responses to insulin by healthy adult control (n = 16) and subjects with T1DM (n = 15) without clinical microvascular disease. We measured insulin's effect on 1) skeletal muscle microvascular perfusion using contrast-enhanced ultrasound (CEU), 2) arterial stiffness using carotid-femoral pulse-wave velocity (cfPWV) and radial artery pulse wave analysis (PWA), and 3) metabolic insulin sensitivity by the glucose infusion rate (GIR) during a 2-h, 1 mU/min/kg euglycemic-insulin clamp. Subjects with T1DM were metabolically insulin resistant (GIR = 5.2 ± 0.7 vs. 6.6 ± 0.6 mg/min/kg, P < 0.001). Insulin increased muscle microvascular blood volume and flow in control (P < 0.001, for each) but not in subjects with T1DM. Metabolic insulin sensitivity correlated with increases of muscle microvascular perfused volume (P < 0.05). Baseline measures of vascular stiffness did not differ between groups. However, during hyperinsulinemia, cfPWV was greater (P < 0.02) in the T1DM group and the backward pulse wave pressure declined with insulin only in controls (P < 0.03), both indices indicating that insulin-induced vascular relaxation in controls only. Subjects with T1DM have muscle microvascular insulin resistance that may precede clinical microvascular disease.NEW & NOTEWORTHY Using contrast ultrasound and measures of vascular stiffness, we compared vascular and metabolic responses to insulin in patients with type 1 diabetes with age-matched controls. The patients with type 1 diabetes demonstrated both vascular and metabolic insulin resistance with more than half of the patients with diabetes having a paradoxical vasoconstrictive vascular response to insulin.
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Affiliation(s)
- Linda A Jahn
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
| | - Lee M Hartline
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
| | - Amanda J Kleiner
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
| | - William B Horton
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
| | - Farhad Hasan
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
| | - Alvin Wai Kit Tan
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
| | - Zhenqi Liu
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
| | - Eugene J Barrett
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
- Department of Pharmacology, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
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15
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Stougaard EB, Rossing P, Vistisen D, Banks P, Girard M, Davies MJ, Persson F. Sotagliflozin, a dual sodium-glucose co-transporter-1 and sodium-glucose co-transporter-2 inhibitor, reduces the risk of cardiovascular and kidney disease, as assessed by the Steno T1 Risk Engine in adults with type 1 diabetes. Diabetes Obes Metab 2023. [PMID: 36872068 DOI: 10.1111/dom.15047] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 02/28/2023] [Accepted: 03/02/2023] [Indexed: 03/07/2023]
Abstract
AIMS Sotagliflozin (SOTA) as adjunct to insulin therapy improves glycemic control, reduces body weight and blood pressure, and increases time in range in adults with type 1 diabetes (T1D). SOTA demonstrated CV and kidney benefits in high-risk adults with type 2 diabetes. These potential benefits using SOTA for T1D may collectively outweigh the risk of diabetic ketoacidosis. The present analysis estimated the risk of CVD and kidney failure in adults with T1D treated with SOTA. MATERIALS AND METHODS Participant-level data were used from the inTandem trials evaluating 2980 adults with T1D randomized to once-daily placebo, SOTA 200 mg, or SOTA 400 mg for 24 weeks. For each participant, the cumulative risks of developing CVD and kidney failure were estimated using the Steno T1 Risk Engine. A subgroup analysis was performed in participants with BMI ≥ 27 kg/m2 . RESULTS SOTA significantly reduced the predicted 5- and 10-year CVD risk in the SOTA 200 and 400 mg pooled group with a relative change in the SOTA group compared to the relative change in the placebo group of (mean [95%-confidence interval (CI)]) -6.6 (-7.9, -5.3) % and -6.4 (-7.6, -5.1) % (p < 0.0001 for both) respectively. For the 5-year ESKD risk there was a significant reduction with a relative change of -5.0 (-7.6, -2.3) % (p = 0.0003). Similar results were observed with the individual doses and in participants with BMI ≥ 27 kg/m2 . CONCLUSION This analysis provides additional clinical results that may positively balance the benefit/risk assessment of SGLT inhibition use in T1D.
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Affiliation(s)
| | - Peter Rossing
- Complication Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, University of Copenhagen, Herlev, Denmark
| | - Dorte Vistisen
- Clinical Epidemiology, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Public Health, University of Copenhagen, Herlev, Denmark
| | - Phillip Banks
- Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA
| | - Manon Girard
- Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA
| | | | - Frederik Persson
- Complication Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
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16
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Tang X, Yan X, Zhou H, Huang G, Niu X, Jiang H, Su H, Yang X, Li X, Zhou Z. Associations of insulin resistance and beta-cell function with abnormal lipid profile in newly diagnosed diabetes. Chin Med J (Engl) 2022; 135:2554-2562. [PMID: 35245924 PMCID: PMC9944004 DOI: 10.1097/cm9.0000000000002075] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Abnormal lipids are strong predictors of cardiovascular disease in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). However, the potential associations of insulin resistance (IR) and beta-cell function (BCF) with abnormal lipids in newly diagnosed T1DM or T2DM patients are not fully understood. METHODS A cross-sectional survey of 15,928 participants was conducted. Homeostasis model assessment and postprandial C-peptide levels were used to estimate IR and BCF. A restricted cubic spline (RCS) nested in binary logistic regression was used to examine the associations of IR and BCF with abnormal lipids. RESULTS High triglyceride (TG), low high-density lipoprotein cholesterol, and high low-density lipoprotein cholesterol (LDL-C) accounted for 49.7%, 47.8%, and 59.2% of the participants, respectively. In multivariable analysis, high IR was associated with an increased risk of high TGs ( P for trend <0.001) in T1DM and is associated with an elevated risk of high TG and low HDL-C (all P for trend <0.01) in T2DM. Low BCF was not associated with risks of dyslipidemia in patients with T1DM or T2DM after adjustment for potential confounders. CONCLUSION High IR had different associations with the risk of dyslipidemia in newly diagnosed T1DM and T2DM patients, suggesting that early treatment that improves IR may benefit abnormal lipid metabolism.
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Affiliation(s)
- Xiaohan Tang
- Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China
| | - Xiang Yan
- Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China
| | - Houde Zhou
- Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China
| | - Gan Huang
- Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China
| | - Xiaohong Niu
- Department of Endocrinology, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi 046000, China
| | - Hongwei Jiang
- Department of Endocrinology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan 471003, China
| | - Heng Su
- Department of Endocrinology, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan, Kunming, Yunnan 650032, China
| | - Xilin Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin 300070, China
| | - Xia Li
- Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China
| | - Zhiguang Zhou
- Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China
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Stougaard EB, Rossing P, Cherney D, Vistisen D, Persson F. Sodium-glucose cotransporter 2 inhibitors as adjunct therapy for type 1 diabetes and the benefit on cardiovascular and renal disease evaluated by Steno risk engines. J Diabetes Complications 2022; 36:108257. [PMID: 35840519 DOI: 10.1016/j.jdiacomp.2022.108257] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 06/28/2022] [Accepted: 07/01/2022] [Indexed: 11/23/2022]
Abstract
AIMS Sodium-glucose cotransporter inhibitors (SGLTi) have beneficial cardiovascular and renal effects in persons with type 2 diabetes. No studies have shown whether this can be demonstrated in type 1 diabetes (T1D). We aimed to estimate the risk of cardiovascular disease (CVD) and end-stage kidney disease (ESKD) in persons with T1D with and without treatment with SGLTi. METHODS The study is based on 3660 adults with T1D. The Steno Type 1 Risk Engines were used to calculate 5-year risks of ESKD and 5- and 10-year risk of CVD. The effect of SGLTi was simulated by changing the HbA1c and systolic blood pressure values in accordance with results from the DEPICT studies with mean (standard deviation (SD)) of -3.6 (0.9) mmol/mol (-2.5 % (2.2)) and -1.12 (2.8) mmHg. eGFR and albuminuria were changed in accordance with results from the Tandem studies; no change in eGFR and mean (SD) %-change in albuminuria of -23.7 (12.9). RESULTS We found a 5-year CVD relative risk reduction of 6.1 % (95%CI 5.9,6.3) and 11.1 % (10.0,12.2) in the subgroup with albuminuria with similar results for the 10-year CVD risk. For the estimated 5-year risk of ESKD, we found a relative risk reduction of 5.3 % (5.1,5.4) with 7.6 % (6.9,8.4) in the subgroup with albuminuria. CONCLUSION We found a significant CVD and ESKD risk reduction, especially in the subgroup with albuminuria.
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Affiliation(s)
| | - Peter Rossing
- Complication Research, Steno Diabetes Center Copenhagen, Capital Region, Denmark; Department of Clinical Medicine, University of Copenhagen, Capital Region, Denmark
| | - David Cherney
- Department of Medicine, University of Toronto, Division of Nephrology, Toronto, Ontario, Canada; Toronto General Hospital Research Institute, Toronto, Ontario, Canada
| | - Dorte Vistisen
- Clinical Epidemiology, Steno Diabetes Center Copenhagen, Capital Region, Denmark; Department of Public Health, University of Copenhagen, Capital Region, Denmark
| | - Frederik Persson
- Complication Research, Steno Diabetes Center Copenhagen, Capital Region, Denmark
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18
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Rodriguez-Loureiro L, Casas L, Bauwelinck M, Lefebvre W, Vanpoucke C, Gadeyne S. Long-term exposure to objective and perceived residential greenness and diabetes mortality: A census-based cohort study. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 821:153445. [PMID: 35093349 DOI: 10.1016/j.scitotenv.2022.153445] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 01/17/2022] [Accepted: 01/22/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Residing close to green spaces might reduce diabetes mellitus (DM) risk; however, evidence for diabetes mortality is limited. Moreover, individual and neighbourhood social factors may determine DM risk. Exposure to green spaces may also depend on socioeconomic position (SEP). This study examined the associations between residential greenness and diabetes-related mortality, and the role of the social environment in these associations. METHODS We used the 2001 Belgian census linked to mortality register data for the period 2001-2014. We included individuals aged 40-79 years old and residing in the five largest Belgian urban areas at baseline. Exposure to residential greenness was assessed with surrounding greenness using the Normalized Difference Vegetation Index (NDVI) within 500-m of residence (objective indicator), and perceived neighbourhood greenness (subjective indicator). We conducted mixed-effects Cox proportional hazards models to obtain hazard ratios (HR) for diabetes-related mortality per interquartile range (IQR) increments of residential greenness. We assessed effect modification by social factors through stratification. RESULTS From 2,309,236 individuals included at baseline, 1.2% died from DM during follow-up. Both residential greenness indicators were inversely associated with diabetes-related mortality after adjustment for individual social factors. After controlling for neighbourhood SEP, the beneficial association with surrounding greenness disappeared [HR 1.02 (95%CI:0.99,1.06)], but persisted with perceived neighbourhood greenness [HR 0.93 (95%CI:0.91,0.95)]. After stratification the inverse associations with perceived neighbourhood greenness were strongest for women, the lowest educated, and individuals residing in least deprived neighbourhoods. CONCLUSIONS Our findings suggest that an overall positive perception of neighbourhood green spaces reduces independently the risk of diabetes-related mortality, regardless of the neighbourhood social environment. Nevertheless, neighbourhood SEP may be a strong confounder in the associations between diabetes-related mortality and greenness indicators derived from satellite images. Perception factors not captured by objective measurements of green spaces are potentially relevant in the association with DM, especially among disadvantaged groups.
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Affiliation(s)
- Lucía Rodriguez-Loureiro
- Interface Demography, Department of Sociology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
| | - Lidia Casas
- Social Epidemiology and Health Policy, Department of Family Medicine and Population Health, University of Antwerp, Gouverneur Kinsbergencentrum, Doornstraat 331, 2610 Wilrijk, Belgium; Institute for Environment and Sustainable Development (IMDO), University of Antwerp, Campus Groenenborger, Groenenborgerlaan 171, 2020 Antwerp, Belgium
| | - Mariska Bauwelinck
- Interface Demography, Department of Sociology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
| | - Wouter Lefebvre
- Flemish Institute for Technological Research (VITO), Boeretang 200, 2400 Mol, Belgium
| | - Charlotte Vanpoucke
- Belgian Interregional Environment Agency (IRCELINE), Gaucheretstraat 92-94, 1030 Brussels, Belgium
| | - Sylvie Gadeyne
- Interface Demography, Department of Sociology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
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19
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Saeed M, Stene LC, Ariansen I, Tell GS, Tapia G, Joner G, Skrivarhaug T. Nine-fold higher risk of acute myocardial infarction in subjects with type 1 diabetes compared to controls in Norway 1973-2017. Cardiovasc Diabetol 2022; 21:59. [PMID: 35477506 PMCID: PMC9047315 DOI: 10.1186/s12933-022-01498-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 04/09/2022] [Indexed: 02/27/2023] Open
Abstract
BACKGROUND We aimed to study the cumulative incidence and risk factors (sex, age, calendar year of diabetes onset, country of origin and educational level) of acute myocardial infarction (AMI) in subjects with type 1 diabetes and matched controls. METHODS A nationwide cohort of subjects with type 1 diabetes diagnosed at age < 15 years in Norway during 1973-2000 was followed until the first AMI event, emigration, death or 31st of December 2017. The Norwegian Childhood Diabetes Registry was linked to five nationwide registries, and up to ten sex- and age-matched controls per case were included. RESULTS Among 7086 subjects with type 1 diabetes, 170 (2.4%) were identified with incident AMI, compared to 193 (0.3%) of 69,356 controls. Mean age and diabetes duration at first AMI was 40.8 years and 30.6 years, respectively. The probability of AMI after 40 years of follow-up was 8.0% in subjects with type 1 diabetes and 1.1% in controls, aHR 9.05 (95% CI 7.18-11.41). In type 1 diabetes, male sex (aHR 1.45), higher age at onset of diabetes and lower education (higher compared to lower, aHR 0.38) were significantly associated with higher risk of AMI. There was no significant time trend in AMI by calendar year of diabetes onset. CONCLUSIONS We found nine-fold excess risk of AMI in subjects with type 1 diabetes, and three-fold higher risk in subjects with low versus high education. These results highlight a strengthened focus on prevention of cardiovascular disease, and diabetes education tailored to the subjects' educational background.
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Affiliation(s)
- Maryam Saeed
- Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway. .,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. .,Oslo Diabetes Research Centre, Oslo University Hospital, Oslo, Norway.
| | - Lars C Stene
- Oslo Diabetes Research Centre, Oslo University Hospital, Oslo, Norway.,Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway
| | - Inger Ariansen
- Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway
| | - Grethe S Tell
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
| | - German Tapia
- Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway
| | - Geir Joner
- Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Torild Skrivarhaug
- Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.,Oslo Diabetes Research Centre, Oslo University Hospital, Oslo, Norway
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20
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Wake AD. Protective effects of physical activity against health risks associated with type 1 diabetes: "Health benefits outweigh the risks". World J Diabetes 2022; 13:161-184. [PMID: 35432757 PMCID: PMC8984568 DOI: 10.4239/wjd.v13.i3.161] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 12/08/2021] [Accepted: 02/20/2022] [Indexed: 02/06/2023] Open
Abstract
The magnitude of diabetes mellitus (DM) has increased in recent decades, where the number of cases and the proportion of the disease have been gradually increasing over the past few decades. The chronic complications of DM affect many organ systems and account for the majority of morbidity and mortality associated with the disease. The prevalence of type 1 DM (T1DM) is increasing globally, and it has a very significant burden on countries and at an individual level. T1DM is a chronic illness that requires ongoing medical care and patient self-management to prevent complications. This study aims to discuss the health benefits of physical activity (PA) in T1DM patients. The present review article was performed following a comprehensive literature search. The search was conducted using the following electronic databases: "Cochrane Library", Web of Science, PubMed, HINARI, EMBASE, Google for grey literature, Scopus, African journals Online, and Google Scholar for articles published up to June 21, 2021. The present review focused on the effects of PA on many outcomes such as blood glucose (BG) control, physical fitness, endothelial function, insulin sensitivity, well-being, the body defense system, blood lipid profile, insulin resistance, cardiovascular diseases (CVDs), insulin requirements, blood pressure (BP), and mortality. It was found that many studies recommended the use of PA for the effective management of T1DM. PA is a component of comprehensive lifestyle modifications, which is a significant approach for the management of T1DM. It provides several health benefits, such as improving BG control, physical fitness, endothelial function, insulin sensitivity, well-being, and the body defense system. Besides this, it reduces the blood lipid profile, insulin resistance, CVDs, insulin requirements, BP, and mortality. Overall, PA has significant and essential protective effects against the health risks associated with T1DM. Even though PA has several health benefits for patients with T1DM, these patients are not well engaged in PA due to barriers such as a fear of exercise-induced hypoglycemia in particular. However, several effective strategies have been identified to control exercise-induced hypoglycemia in these patients. Finally, the present review concludes that PA should be recommended for the management of patients with T1DM due to its significant health benefits and protective effects against associated health risks. It also provides suggestions for the future direction of research in this field.
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Affiliation(s)
- Addisu Dabi Wake
- Department of Nursing, College of Health Sciences, Arsi University, Asella 193/4, Ethiopia
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21
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Zhu B, Qu S. The Relationship Between Diabetes Mellitus and Cancers and Its Underlying Mechanisms. Front Endocrinol (Lausanne) 2022; 13:800995. [PMID: 35222270 PMCID: PMC8873103 DOI: 10.3389/fendo.2022.800995] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Accepted: 01/12/2022] [Indexed: 12/27/2022] Open
Abstract
Epidemiological studies suggest associations between diabetes mellitus and some cancers. The risk of a number of cancers appears to be increased in diabetes mellitus. On the other hand, some cancer and cancer therapies could lead to diabetes mellitus. Genetic factors, obesity, inflammation, oxidative stress, hyperglycemia, hyperinsulinemia, cancer therapies, insulin and some oral hypoglycemic drugs appear to play a role in the crosstalk between diabetes mellitus and cancers. This review summarized the associations between various types of diabetes and cancers and updated available evidence of underlying mechanisms between diabetes and cancers.
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Affiliation(s)
| | - Shen Qu
- Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China
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22
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Jahn LA, Logan B, Love KM, Horton WB, Eichner NZ, Hartline LM, Weltman AL, Barrett EJ. Nitric oxide-dependent micro- and macrovascular dysfunction occurs early in adolescents with type 1 diabetes. Am J Physiol Endocrinol Metab 2022; 322:E101-E108. [PMID: 34894721 PMCID: PMC8799398 DOI: 10.1152/ajpendo.00267.2021] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 11/16/2021] [Accepted: 12/05/2021] [Indexed: 11/22/2022]
Abstract
Arterial stiffness and endothelial dysfunction are both reported in children with type 1 diabetes (DM1) and may predict future cardiovascular events. In health, nitric oxide (NO) relaxes arteries and increases microvascular perfusion. The relationships between NO-dependent macro- and microvascular functional responses and arterial stiffness have not been studied in adolescents with DM1. Here, we assessed macro- and microvascular function in DM1 adolescents and age-matched controls at baseline and during an oral glucose challenge (OGTT). DM1 adolescents (n = 16) and controls (n = 14) were studied before and during an OGTT. At baseline, we measured: 1) large artery stiffness using both aortic augmentation index (AI) and carotid-femoral pulse wave velocity (cfPWV); 2) brachial flow-mediated dilation (FMD) and forearm endothelial function using postischemic flow velocity (PIFV); and 3) forearm muscle microvascular blood volume (MBV) using contrast-enhanced ultrasound. Following OGTT, AI, cfPWV, and MBV were reassessed at 60 min and MBV again at 120 min. Within individual and between-group, comparisons were made by paired and unpaired t tests or repeated measures ANOVA. Baseline FMD was lower (P = 0.02) in DM1. PWV at 0 and 60 min did not differ between groups. Baseline AI did not differ between groups but declined with OGTT only in controls (P = 0.02) and was lower than DM1 at 60 min (P < 0.03). Baseline MBV was comparable in DM1 and control groups, but declined in DM1 at 120 min (P = 0.01) and was lower than the control group (P < 0.03). There was an inverse correlation between plasma glucose and MBV at 120 min (r = -0.523, P < 0.01). No differences were noted between groups for V̇O2max (mL/min/kg), body fat (%), or body mass index (BMI). NO-dependent macro- and microvascular function, including FMD and AI, and microvascular perfusion, respectively, are impaired early in the course of DM1, precede increases of arterial stiffness, and may provide an early indicator of vascular risk.NEW & NOTEWORTHY This is the first study to show that type 1 diabetes impairs multiple nitric oxide-dependent vascular functions.
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Affiliation(s)
- Linda A Jahn
- Department of Medicine, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
| | - Brent Logan
- Department of Pediatrics, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
| | - Kaitlin M Love
- Department of Medicine, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
| | - William B Horton
- Department of Medicine, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
| | - Natalie Z Eichner
- Department of Kinesiology, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
| | - Lee M Hartline
- Department of Medicine, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
| | - Arthur L Weltman
- Department of Medicine, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
- Department of Kinesiology, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
| | - Eugene J Barrett
- Department of Medicine, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
- Department of Pediatrics, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
- Department of Pharmacology, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
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23
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Kardiovaskuläre Risiken in der 4.–6. Lebensdekade mit Diabetes mellitus Typ 1. DIABETOLOGE 2022. [DOI: 10.1007/s11428-021-00854-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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24
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HDL and Diabetes. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1377:119-127. [DOI: 10.1007/978-981-19-1592-5_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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25
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Polak JF, Backlund JYC, Budoff M, Raskin P, Bebu I, Lachin JM. Coronary Artery Disease Events and Carotid Intima-Media Thickness in Type 1 Diabetes in the DCCT/EDIC Cohort. J Am Heart Assoc 2021; 10:e022922. [PMID: 34873921 PMCID: PMC9075257 DOI: 10.1161/jaha.121.022922] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background Carotid artery intima‐media thickness (IMT) is associated with the risk of subsequent cardiovascular events in the general population. This association has not been established in type 1 diabetes. Methods and Results We studied if carotid IMT is associated with the risk of a first coronary artery disease event in participants with type 1 diabetes in the EDIC (Epidemiology of Diabetes Interventions and Complications) study, the long‐term observational follow‐up of the DCCT (Diabetes Control and Complications Trial). Between 1994 and 1996, common carotid artery and internal carotid artery IMT were measured with high‐resolution ultrasound in 1309 study participants with a mean age of 35 years and diabetes duration of 13.8 years; 52% were men. Cox proportional hazards models evaluated the association of standardized common carotid artery IMT and internal carotid artery IMT with subsequent cardiovascular events over the next 17 years. Models were adjusted for age, sex, mean hemoglobin A1c levels, and traditional cardiovascular risk factors. Associations of common carotid artery IMT with subsequent CAD were significant after adjustment for imaging device, sex, and age (hazard ratio [HR], 1.23 per 0.09 mm [95% CI, [1.04–1.45]; P=0.0141), but did not remain significant after further adjustment for traditional risk factors and hemoglobin A1c (HR, 1.14 per 0.09 mm [95% CI, 0.97–1.33]; P=0.1206). No significant associations with subsequent coronary artery disease events were seen for internal carotid artery IMT. Conclusions In the DCCT/EDIC cohort with type 1 diabetes, common carotid artery IMT, but not internal carotid artery IMT, is weakly associated with subsequent coronary artery events, an association eliminated after adjusting for coexistent traditional cardiovascular risk factors. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00360815 and NCT00360893.
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Affiliation(s)
- Joseph F Polak
- Department of Radiology Lemuel Shattuck HospitalTufts University School of Medicine and Boston University School of Medicine Boston MA
| | - Jye-Yu C Backlund
- The Biostatistics Center The George Washington University Rockville MD
| | - Matt Budoff
- UCLA School of MedicineLos Angeles Biomedical Research Institute Torrance CA
| | - Philip Raskin
- University of Texas Southwestern Medical Center Dallas TX
| | - Ionut Bebu
- The Biostatistics Center The George Washington University Rockville MD
| | - John M Lachin
- The Biostatistics Center The George Washington University Rockville MD
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Piemonti L. Felix dies natalis, insulin… ceterum autem censeo "beta is better". Acta Diabetol 2021; 58:1287-1306. [PMID: 34027619 DOI: 10.1007/s00592-021-01737-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 05/06/2021] [Indexed: 12/12/2022]
Abstract
One hundred years after its discovery, insulin remains the life-saving therapy for many patients with diabetes. It has been a 100-years-old success story thanks to the fact that insulin therapy has continuously integrated the knowledge developed over a century. In 1982, insulin becomes the first therapeutic protein to be produced using recombinant DNA technology. The first "mini" insulin pump and the first insulin pen become available in 1983 and 1985, respectively. In 1996, the first generation of insulin analogues were produced. In 1999, the first continuous glucose-monitoring device for reading interstitial glucose was approved by the FDA. In 2010s, the ultra-long action insulins were introduced. An equally exciting story developed in parallel. In 1966. Kelly et al. performed the first clinical pancreas transplant at the University of Minnesota, and now it is a well-established clinical option. First successful islet transplantations in humans were obtained in the late 1980s and 1990s. Their ability to consistently re-establish the endogenous insulin secretion was obtained in 2000s. More recently, the possibility to generate large numbers of functional human β cells from pluripotent stem cells was demonstrated, and the first clinical trial using stem cell-derived insulin producing cell was started in 2014. This year, the discovery of this life-saving hormone turns 100 years. This provides a unique opportunity not only to celebrate this extraordinary success story, but also to reflect on the limits of insulin therapy and renew the commitment of the scientific community to an insulin free world for our patients.
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Affiliation(s)
- Lorenzo Piemonti
- San Raffaele Diabetes Research Institute, San Raffaele Scientific Institute, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
- Università Vita-Salute San Raffaele, Milan, Italy.
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C Thambiah S, Lai LC. Diabetic dyslipidaemia. Pract Lab Med 2021; 26:e00248. [PMID: 34368411 PMCID: PMC8326412 DOI: 10.1016/j.plabm.2021.e00248] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 05/16/2021] [Accepted: 07/14/2021] [Indexed: 12/22/2022] Open
Abstract
Diabetes mellitus (DM) is an escalating pandemic and an established cardiovascular risk factor. An important aspect of the interaction between DM and atherosclerotic cardiovascular disease (ASCVD) is diabetic dyslipidaemia, an atherogenic dyslipidaemia encompassing quantitative [hypertriglyceridaemia (hyperTG) and decreased high density lipoprotein cholesterol (HDL)] and qualitative [increased small dense low density lipoprotein cholesterol (sdLDL) particles, large very low density lipoprotein cholesterol (VLDL) subfraction (VLDL1) and dysfunctional HDL] modifications in lipoproteins. Much of the pathophysiology linking DM and dyslipidaemia has been elucidated. This paper aims to review the pathophysiology and management of diabetic dyslipidaemia with respect to ASCVD. Briefly, the influence of diabetic kidney disease on lipid profile and lipid changes causing type 2 diabetes mellitus are highlighted. Biomarkers of diabetic dyslipidaemia, including novel markers and clinical trials that have demonstrated that non-lipid and lipid lowering therapies can lower cardiovascular risk in diabetics are discussed. The stands of various international guidelines on lipid management in DM are emphasised. It is important to understand the underlying mechanisms of diabetic dyslipidaemia in order to develop new therapeutic strategies against dyslipidaemia and diabetes. The various international guidelines on lipid management can be used to tailor a holistic approach specific to each patient with diabetic dyslipidaemia.
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Affiliation(s)
- Subashini C Thambiah
- Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia
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Timmons JG, Greenlaw N, Boyle JG, Chaturvedi N, Ford I, Brouwers MCGJ, Tillin T, Hramiak I, Hughes AD, Jenkins AJ, Klein BEK, Klein R, Ooi TC, Rossing P, Stehouwer CDA, Sattar N, Colhoun HM, Petrie JR. Metformin and carotid intima-media thickness in never-smokers with type 1 diabetes: The REMOVAL trial. Diabetes Obes Metab 2021; 23:1371-1378. [PMID: 33591613 DOI: 10.1111/dom.14350] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 01/29/2021] [Accepted: 02/09/2021] [Indexed: 02/05/2023]
Abstract
AIM To determine whether metformin's effects on carotid artery intima-media thickness (cIMT) in type 1 diabetes differ according to smoking status. METHODS Regression model effect estimates for the effect of metformin versus placebo (double-blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial. RESULTS In 428 randomized participants (227 never-smokers, 201 ever-smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (-0.012 mm, 95% CI -0.021 to -0.002; p = .0137) but not in ever-smokers (0.003 mm, 95% CI -0.008 to 0.014; p = .5767); and similarly in non-current smokers (-0.008 mm, 95% CI -0.015 to -0.00001; p = .0497) but not in current smokers (0.013 mm, 95% CI -0.007 to 0.032; p = .1887). Three-way interaction terms (treatment*time*smoking status) were significant for never versus ever smoking (p = .0373, prespecified) and non-current versus current smoking (p = .0496, exploratory). Averaged maximal carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (-0.020 mm, 95% CI -0.034 to -0.006; p = .0067) but not in ever-smokers (-0.006 mm, 95% CI -0.020 to 0.008; p = .4067), although this analysis was not supported by a significant three-way interaction term. CONCLUSIONS This subgroup analysis of the REMOVAL trial provides additional support for a potentially wider role of adjunct metformin therapy in cardiovascular risk management in type 1 diabetes, particularly for individuals who have never smoked cigarettes.
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Affiliation(s)
- Joseph G Timmons
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Nicola Greenlaw
- Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK
| | - James G Boyle
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Nish Chaturvedi
- Institute of Cardiovascular Science, University College London, London, UK
| | - Ian Ford
- Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK
| | - Martijn C G J Brouwers
- Department of Internal Medicine and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Therese Tillin
- Institute of Cardiovascular Science, University College London, London, UK
| | | | - Alun D Hughes
- Institute of Cardiovascular Science, University College London, London, UK
| | - Alicia J Jenkins
- NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia
| | - Barbara E K Klein
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Ron Klein
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Teik C Ooi
- Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Peter Rossing
- Steno Diabetes Center Copenhagen and the University of Copenhagen, Copenhagen, Denmark
| | - Coen D A Stehouwer
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands; and, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Helen M Colhoun
- Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - John R Petrie
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
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Cardiovascular Disease in Type 1 Diabetes Mellitus: Epidemiology and Management of Cardiovascular Risk. J Clin Med 2021; 10:jcm10081798. [PMID: 33924265 PMCID: PMC8074744 DOI: 10.3390/jcm10081798] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/09/2021] [Accepted: 04/18/2021] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes mellitus (T1DM) patients, and cardiovascular risk (CVR) remains high even in T1DM patients with good metabolic control. The underlying mechanisms remain poorly understood and known risk factors seem to operate differently in T1DM and type 2 diabetes mellitus (T2DM) patients. However, evidence of cardiovascular risk assessment and management in T1DM patients often is extrapolated from studies on T2DM patients or the general population. In this review, we examine the existing literature about the prevalence of clinical and subclinical CVD, as well as current knowledge about potential risk factors involved in the development and progression of atherosclerosis in T1DM patients. We also discuss current approaches to the stratification and therapeutic management of CVR in T1DM patients. Chronic hyperglycemia plays an important role, but it is likely that other potential factors are involved in increased atherosclerosis and CVD in T1DM patients. Evidence on the estimation of 10-year and lifetime risk of CVD, as well as the efficiency and age at which current cardiovascular medications should be initiated in young T1DM patients, is very limited and clearly insufficient to establish evidence-based therapeutic approaches to CVD management.
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Savic D, Ball V, Holzner L, Hauton D, Timm KN, Curtis MK, Heather LC, Tyler DJ. Hyperpolarized magnetic resonance shows that the anti-ischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved post-ischemic function in the diabetic heart. NMR IN BIOMEDICINE 2021; 34:e4471. [PMID: 33458907 PMCID: PMC8609426 DOI: 10.1002/nbm.4471] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 11/20/2020] [Accepted: 12/20/2020] [Indexed: 05/07/2023]
Abstract
The diabetic heart has a decreased ability to metabolize glucose. The anti-ischemic drug meldonium may provide a route to counteract this by reducing l-carnitine levels, resulting in improved cardiac glucose utilization. Therefore, the aim of this study was to use the novel technique of hyperpolarized magnetic resonance to investigate the in vivo effects of treatment with meldonium on cardiac metabolism and function in control and diabetic rats. Thirty-six male Wistar rats were injected either with vehicle, or with streptozotocin (55 mg/kg) to induce a model of type 1 diabetes. Daily treatment with either saline or meldonium (100 mg/kg/day) was undertaken for three weeks. in vivo cardiac function and metabolism were assessed with CINE MRI and hyperpolarized magnetic resonance respectively. Isolated perfused hearts were challenged with low-flow ischemia/reperfusion to assess the impact of meldonium on post-ischemic recovery. Meldonium had no significant effect on blood glucose concentrations or on baseline cardiac function. However, hyperpolarized magnetic resonance revealed that meldonium treatment elevated pyruvate dehydrogenase flux by 3.1-fold and 1.2-fold in diabetic and control animals, respectively, suggesting an increase in cardiac glucose oxidation. Hyperpolarized magnetic resonance further demonstrated that meldonium reduced the normalized acetylcarnitine signal by 2.1-fold in both diabetic and control animals. The increase in pyruvate dehydrogenase flux in vivo was accompanied by an improvement in post-ischemic function ex vivo, as meldonium elevated the rate pressure product by 1.3-fold and 1.5-fold in the control and diabetic animals, respectively. In conclusion, meldonium improves in vivo pyruvate dehydrogenase flux in the diabetic heart, contributing to improved cardiac recovery after ischemia.
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Affiliation(s)
- Dragana Savic
- Cardiac Metabolism Research Group (CMRG), Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK
- Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of MedicineUniversity of OxfordOxfordUK
| | - Vicky Ball
- Cardiac Metabolism Research Group (CMRG), Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK
| | - Lorenz Holzner
- Department of Physiology, Development and NeuroscienceUniversity of CambridgeCambridgeUK
| | - David Hauton
- Cardiac Metabolism Research Group (CMRG), Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK
- Metabolomics Research Group, Department of ChemistryUniversity of OxfordOxfordUK
| | - Kerstin N. Timm
- Cardiac Metabolism Research Group (CMRG), Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK
| | - M. Kate Curtis
- Cardiac Metabolism Research Group (CMRG), Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK
| | - Lisa C. Heather
- Cardiac Metabolism Research Group (CMRG), Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK
| | - Damian J. Tyler
- Cardiac Metabolism Research Group (CMRG), Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK
- Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of MedicineUniversity of OxfordOxfordUK
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31
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Volsky SK, Shalitin S, Fridman E, Yackobovitch-Gavan M, Lazar L, Bello R, Oron T, Tenenbaum A, Vries LD, Lebenthal Y. Dyslipidemia and cardiovascular disease risk factors in patients with type 1 diabetes: A single-center experience. World J Diabetes 2021; 12:56-68. [PMID: 33520108 PMCID: PMC7807252 DOI: 10.4239/wjd.v12.i1.56] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 11/03/2020] [Accepted: 11/18/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Type 1 diabetes (T1D) contributes to altered lipid profiles and increases the risk of cardiovascular disease (CVD). Youth with T1D may have additional CVD risk factors within the first decade of diagnosis.
AIM To examine risk factors for dyslipidemia in young subjects with T1D.
METHODS Longitudinal and cross-sectional retrospective study of 170 young subjects with T1D (86 males; baseline mean age 12.2 ± 5.6 years and hemoglobin A1c 8.4% ± 1.4%) were followed in a single tertiary diabetes center for a median duration of 15 years. Predictors for outcomes of lipid profiles at last visit (total cholesterol [TC], triglycerides [TGs], low-density lipoprotein-cholesterol [LDL-c], and high-density lipoprotein-cholesterol [HDL-c]) were analyzed by stepwise linear regression models.
RESULTS At baseline, 79.5% of the patients had at least one additional CVD risk factor (borderline dyslipidemia/dyslipidemia [37.5%], pre-hypertension/hypertension [27.6%], and overweight/obesity [16.5%]) and 41.6% had multiple (≥ 2) CVD risk factors. A positive family history of at least one CVD risk factor in a first-degree relative was reported in 54.1% of the cohort. Predictors of elevated TC: family history of CVD (β[SE] = 23.1[8.3], P = 0.006); of elevated LDL-c: baseline diastolic blood pressure (DBP) (β[SE] = 11.4[4.7], P = 0.003) and family history of CVD (β[SE] = 20.7[6.8], P = 0.017); of elevated TGs: baseline DBP (β[SE] = 23.8[9.1], P = 0.010) and family history of CVD (β[SE] = 31.0[13.1], P = 0.020); and of low HDL-c levels: baseline DBP (β[SE] = 4.8[2.1], P = 0.022]).
CONCLUSION Our findings suggest that elevated lipid profiles are associated with DBP and a positive family history of CVD. It is of utmost importance to prevent and control modifiable risk factors such as these, as early as childhood, given that inadequate glycemic control and elevation in blood pressure intensify the risk of dyslipidemia.
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Affiliation(s)
- Sari Krepel Volsky
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
| | - Shlomit Shalitin
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Elena Fridman
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
| | - Michal Yackobovitch-Gavan
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
| | - Liora Lazar
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Rachel Bello
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
| | - Tal Oron
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
| | - Ariel Tenenbaum
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Liat de Vries
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Yael Lebenthal
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
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32
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Li PF, Chen WL. Are the Different Diabetes Subgroups Correlated With All-Cause, Cancer-Related, and Cardiovascular-Related Mortality? J Clin Endocrinol Metab 2020; 105:5902292. [PMID: 32893854 DOI: 10.1210/clinem/dgaa628] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 09/01/2020] [Indexed: 12/21/2022]
Abstract
CONTEXT Numerous studies have shown that cardiovascular disease (CVD) represents the most important cause of mortality among people with diabetes mellitus (DM). However, no studies have evaluated the risk of CVD-related mortality among different DM subgroups. OBJECTIVE We aimed to examine all-cause, CVD-related, and cancer-related mortality for different DM subgroups. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS We included participants (age ≥ 20 years) from the National Health and Nutrition Examination Survey III (NHANES III) data set. We evaluated the risks of all-cause and cause-specific (CVD and cancer) mortality among 5 previously defined diabetes subgroups: severe autoimmune diabetes (SAID), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). PRIMARY OUTCOME MEASURE The hazard ratios (HRs) for all-cause and cause-specific (CVD and cancer) mortality were measured for each of the 5 DM subgroups. We also evaluated the odds ratios (ORs) for retinopathy and nephropathy in each subgroup. RESULTS A total of 712 adults were enrolled and the median follow-up time was 12.71 years (range, 0.25-18.08 years). The number of deaths in the 5 subgroups (SAID, SIDD, SIRD, MOD, and MARD) were 50, 75, 64, 7, and 18, respectively, and the number of CVD-related deaths in the 5 subgroups was 29, 30, 26, 2, and 11, respectively. Compared to the MOD subgroup, the adjusted HRs and 95% CIs of CVD-related mortality for the SAID, SIDD, SIRD, and MARD subgroups were 3.23 (95% CI, 0.77-13.61), 2.87 (95% CI, 0.68-12.06), 2.23 (95% CI, 0.53-9.50), and 4.75 (95% CI, 1.05-21.59), respectively (the HR for the MARD subgroup had a P value of .04). In addition, compared to the MARD subgroup, the adjusted ORs and 95% CIs for retinopathy in the SAID and SIDD groups were 2.38 (95% CI, 1.13-5.01, P = .02) and 3.34 (95% CI, 1.17-6.88, P = .001), respectively. The ORs for nephropathy were nonsignificant. CONCLUSIONS Our study of patients from the NHANES III data set indicated that among the different DM subgroups, the MARD subgroup tended to have a higher CVD-related mortality than the MOD subgroup. The all-cause and cancer-related mortality rates were similar across the different diabetes subgroups. In addition, compared to the MARD subgroup, the SAID and SIDD subgroups had a higher retinopathy risk, but there was no difference in nephropathy among the subgroups.
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Affiliation(s)
- Peng-Fei Li
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical School, Taipei, Taiwan, Republic of China
- Graduate Institute of Applied Science and Engineering, Fu-Jen Catholic University, Taipei, Taiwan, Republic of China
| | - Wei-Liang Chen
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
- Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
- Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, Republic of China
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33
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Zhu S, Liu F, Li J, Guan Y, Meng M, Li X, Zhou Z, Xu R, Li L. Development and validation of a self-management scale of type 1 diabetes for Chinese adults. J Int Med Res 2020; 48:300060520947588. [PMID: 32865059 PMCID: PMC7469726 DOI: 10.1177/0300060520947588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Objective Self-management is beneficial for improving health outcomes in adults with type 1 diabetes. However, there are no validated instruments to assess self-management in Chinese adults with type 1 diabetes. The aim of this study was to develop and validate the Self-Management of Type 1 Diabetes for Chinese Adults (SMOD-CA) scale. Methods Qualitative and quantitative methods were used to develop the SMOD-CA. We conducted a literature review and semi-structured interviews to generate an initial item pool. An expert panel examined the content validity. We conducted a cross-sectional survey to evaluate scale reliability and validity. A total of 243 participants were recruited. Exploratory factor analyses were used to test the construct validity, and internal consistency and test-retest reliability were assessed. Results The expert panel determined that the SMOD-CA content validity index was satisfactory. The final 30-item scale consisted of four factors explaining 49.50% of the total variance in the data. Cronbach’s α was 0.901 for the total scale and 0.911 for test–retest reliability. Conclusions The SMOD-CA demonstrated good reliability and validity. The scale is a credible and effective instrument that can be used by social workers and health care professionals to assess self-management in Chinese adults with type 1 diabetes. Trial registration number NCT03610984
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Affiliation(s)
- Song Zhu
- Clinic Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.,Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Fang Liu
- Clinic Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.,Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.,Ministry of Education, National Clinical Research Center for Metabolic Disease, Changsha, China
| | - Jina Li
- Clinic Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.,Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Yuzhu Guan
- Xiangya Nursing School, Central South University, Changsha, Hunan Province, China
| | - Meng Meng
- Xiangya Nursing School, Central South University, Changsha, Hunan Province, China
| | - Xia Li
- Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Zhiguang Zhou
- Ministry of Education, National Clinical Research Center for Metabolic Disease, Changsha, China
| | - Rong Xu
- Clinic Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Lezhi Li
- Clinic Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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Abi-Ghanem C, Robison LS, Zuloaga KL. Androgens' effects on cerebrovascular function in health and disease. Biol Sex Differ 2020; 11:35. [PMID: 32605602 PMCID: PMC7328272 DOI: 10.1186/s13293-020-00309-4] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 05/20/2020] [Indexed: 12/18/2022] Open
Abstract
Androgens affect the cerebral vasculature and may contribute to sex differences in cerebrovascular diseases. Men are at a greater risk for stroke and vascular contributions to cognitive impairment and dementia (VCID) compared to women throughout much of the lifespan. The cerebral vasculature is a target for direct androgen actions, as it expresses several sex steroid receptors and metabolizing enzymes. Androgens’ actions on the cerebral vasculature are complex, as they have been shown to have both protective and detrimental effects, depending on factors such as age, dose, and disease state. When administered chronically, androgens are shown to be pro-angiogenic, promote vasoconstriction, and influence blood-brain barrier permeability. In addition to these direct effects of androgens on the cerebral vasculature, androgens also influence other vascular risk factors that may contribute to sex differences in cerebrovascular diseases. In men, low androgen levels have been linked to metabolic and cardiovascular diseases including hypertension, diabetes, hyperlipidemia, and obesity, which greatly increase the risk of stroke and VCID. Thus, a better understanding of androgens’ interactions with the cerebral vasculature under physiological and pathological conditions is of key importance.
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Affiliation(s)
- Charly Abi-Ghanem
- Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY, 12208, USA
| | - Lisa S Robison
- Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY, 12208, USA
| | - Kristen L Zuloaga
- Department of Neuroscience & Experimental Therapeutics, Albany Medical College, 47 New Scotland Avenue, MC-136, Albany, NY, 12208, USA.
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Błaszkowska M, Shalimova A, Wolnik B, Orłowska-Kunikowska E, Graff B, Hoffmann M, Nilsson P, Wolf J, Narkiewicz K. Subclinical macroangiopathic target organ damage in type 1 diabetes mellitus patients. Blood Press 2020; 29:344-356. [PMID: 32460564 DOI: 10.1080/08037051.2020.1770054] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE We have summarized key studies regarding the assessment of subclinical macroangiopathic target organ damage (TOD) in type 1 diabetes mellitus (T1DM). RESULTS Although chronic complications resulting from hyperglycemia, in particular macroangiopathies, are still the first cause of death in T1DM, there has been growing recognition of the role of hypoglycemia in cardiovascular morbidity and mortality. Subclinical TOD diagnosis ensures early implementation of the complex management aiming at either partial reversal of these complications or at least its downturn. To better identify patients with early TODs, several non-invasive diagnostic techniques are employed, including the ultrasonographic assessment of the intima-media thickness (IMT), computed tomography (CT) for coronary artery calcium (CAC) scores, and pulse wave velocity (PWV) measurement for arterial stiffness evaluation. Various studies reported that T1DM patients present an increased IMT. An increasing IMT fairly correlates with the cardiovascular (CV) events risk even after the adjustment to age, diabetes duration, quality of glucose control as well as the presence of hypertension, and chronic complications. Another, well established marker of the organ damage - CAC score is recommended by ACC/AHA guidelines to assess the overall CV risk in T1DM. Also, the arterial stiffness evaluation with PWV may further improve CV risk prediction, which has been reported in multiple studies including the Framingham Heart Study. CONCLUSIONS There is shortage of data from prospective studies which could confirm the benefits of early treatment initiation based on the presence of the subclinical organ damage in T1DM. Most evidence comes from T2DM trials, where effective preventive measures were identified i.e.: smoking cessation, reasonable blood glucose control, efficacious hypertension treatment, and dyslipidemia management, as well as renoprotection. There is still a field for further research to see if routine assessment of asymptomatic vascular damage and early implementation of aggressive treatment would reduce mortality excess from CVD in T1DM.
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Affiliation(s)
- Magdalena Błaszkowska
- Department of Hypertension and Diabetology, Medical University of Gdansk, Faculty of Medicine, Gdansk, Poland
| | - Anna Shalimova
- Department of Hypertension and Diabetology, Medical University of Gdansk, Faculty of Medicine, Gdansk, Poland.,Department of Internal Medicine N1, Kharkiv National Medical University, Kharkiv, Ukraine
| | - Bogumił Wolnik
- Department of Hypertension and Diabetology, Medical University of Gdansk, Faculty of Medicine, Gdansk, Poland
| | | | - Beata Graff
- Department of Hypertension and Diabetology, Medical University of Gdansk, Faculty of Medicine, Gdansk, Poland
| | - Michał Hoffmann
- Department of Hypertension and Diabetology, Medical University of Gdansk, Faculty of Medicine, Gdansk, Poland
| | - Peter Nilsson
- Department of Clinical Sciences, Lund University, Skane University Hospital, Malmö, Sweden
| | - Jacek Wolf
- Department of Hypertension and Diabetology, Medical University of Gdansk, Faculty of Medicine, Gdansk, Poland
| | - Krzysztof Narkiewicz
- Department of Hypertension and Diabetology, Medical University of Gdansk, Faculty of Medicine, Gdansk, Poland
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Roshandel D, Chen Z, Canty AJ, Bull SB, Natarajan R, Paterson AD. DNA methylation age calculators reveal association with diabetic neuropathy in type 1 diabetes. Clin Epigenetics 2020; 12:52. [PMID: 32248841 PMCID: PMC7132894 DOI: 10.1186/s13148-020-00840-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 03/15/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath's four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. RESULTS Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18-20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E-3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = - 1.99, p = 0.045) and leisure time (β = - 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E-50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. CONCLUSIONS Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.
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Affiliation(s)
- Delnaz Roshandel
- Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada
| | - Zhuo Chen
- Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA, USA
| | - Angelo J Canty
- Department of Mathematics and Statistics, McMaster University, Hamilton, ON, Canada
| | - Shelley B Bull
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Rama Natarajan
- Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA, USA
| | - Andrew D Paterson
- Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
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37
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Garofolo M, Gualdani E, Giannarelli R, Aragona M, Campi F, Lucchesi D, Daniele G, Miccoli R, Francesconi P, Del Prato S, Penno G. Microvascular complications burden (nephropathy, retinopathy and peripheral polyneuropathy) affects risk of major vascular events and all-cause mortality in type 1 diabetes: a 10-year follow-up study. Cardiovasc Diabetol 2019; 18:159. [PMID: 31733651 PMCID: PMC6858978 DOI: 10.1186/s12933-019-0961-7] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 11/01/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Microvascular complications (MC) have been claimed to increase the risk for cardiovascular disease in diabetic subjects. However, the effect of MC burden on the risk of major vascular outcomes and all-cause mortality in type 1 diabetes is still poorly explored. We evaluated the relationship between microvascular complications burden and incidence of major cardiovascular events and all-cause mortality in subjects with type 1 diabetes. METHODS We recruited 774 participants with type 1 diabetes in a single-center observational study over a follow-up of 10.8 ± 2.5 years. Hazard ratios (HR) for cardiovascular outcomes and all-cause death associated with microvascular complications were determined by unadjusted and adjusted Cox regression analysis. RESULTS Out of 774 individuals, 54.9% had no-MC, 32.3% 1 MC, 9.7% 2 MC and 3.1% 3 MC. A total of 54 deaths (7.0%) occurred. Death rate increased from no-MC 2.1% (Ref) to 1 MC 7.2% (HR 3.54 [95% CI 1.59-7.87]), 2 MC 14.7% (HR 6.41 [95% CI 2.65-15.49]) and 3 MC 66.7% (HR 41.73 [95% CI 18.42-94.57], p < 0.0001). After adjustments, HRs were: 1 MC 2.05 (95% CI 0.88-4.76), 2 MC 1.98 (95% CI 0.75-5.21), 3 MC 7.02 (95% CI 2.44-20.20, p = 0.002). Forty-nine subjects (6.7%) had at least one cardiovascular event, and cumulative incidence went from no-MC 2.2% (Ref) to 1 MC 5.0%; (HR 2.27 [95% CI 0.96-5.38]), 2 MC 26.8% (HR 12.88 [95% CI 5.82-28.50]) and 3 MC 40.9% (HR 29.34 [95% CI 11.59-74.25], p < 0.0001). Upon adjustments, HRs were: 1 MC 1.59 (95% CI 0.65-3.88), 2 MC 4.33 (95% CI 1.75-10.74), 3 MC 9.31 (95% CI 3.18-27.25, p < 0.0001). Thirty-five individuals (4.8%) had at least one coronary event, which cumulative incidence increased with MC burden (p < 0.0001). CONCLUSIONS In type 1 diabetes, microvascular complications burden increases in an independent dose-dependent manner the risk of major cardiovascular outcomes and all-cause mortality. The presence and number of microvascular complications should be considered in stratifying overall cardiovascular risk in type 1 diabetes.
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Affiliation(s)
- Monia Garofolo
- Section of Diabetes and Metabolic Disease, Department of Clinical and Experimental Medicine, University of Pisa and Azienda Ospedaliero-Universitaria Pisana, Via Paradisa, 2, 56124, Pisa, Italy
| | - Elisa Gualdani
- Epidemiology Unit, Regional Health Agency (ARS) of Tuscany, Florence, Italy
| | - Rosa Giannarelli
- Section of Diabetes and Metabolic Disease, Department of Clinical and Experimental Medicine, University of Pisa and Azienda Ospedaliero-Universitaria Pisana, Via Paradisa, 2, 56124, Pisa, Italy
| | - Michele Aragona
- Section of Diabetes and Metabolic Disease, Department of Clinical and Experimental Medicine, University of Pisa and Azienda Ospedaliero-Universitaria Pisana, Via Paradisa, 2, 56124, Pisa, Italy
| | - Fabrizio Campi
- Section of Diabetes and Metabolic Disease, Department of Clinical and Experimental Medicine, University of Pisa and Azienda Ospedaliero-Universitaria Pisana, Via Paradisa, 2, 56124, Pisa, Italy
| | - Daniela Lucchesi
- Section of Diabetes and Metabolic Disease, Department of Clinical and Experimental Medicine, University of Pisa and Azienda Ospedaliero-Universitaria Pisana, Via Paradisa, 2, 56124, Pisa, Italy
| | - Giuseppe Daniele
- Section of Diabetes and Metabolic Disease, Department of Clinical and Experimental Medicine, University of Pisa and Azienda Ospedaliero-Universitaria Pisana, Via Paradisa, 2, 56124, Pisa, Italy
| | - Roberto Miccoli
- Section of Diabetes and Metabolic Disease, Department of Clinical and Experimental Medicine, University of Pisa and Azienda Ospedaliero-Universitaria Pisana, Via Paradisa, 2, 56124, Pisa, Italy
| | - Paolo Francesconi
- Epidemiology Unit, Regional Health Agency (ARS) of Tuscany, Florence, Italy
| | - Stefano Del Prato
- Section of Diabetes and Metabolic Disease, Department of Clinical and Experimental Medicine, University of Pisa and Azienda Ospedaliero-Universitaria Pisana, Via Paradisa, 2, 56124, Pisa, Italy.
| | - Giuseppe Penno
- Section of Diabetes and Metabolic Disease, Department of Clinical and Experimental Medicine, University of Pisa and Azienda Ospedaliero-Universitaria Pisana, Via Paradisa, 2, 56124, Pisa, Italy
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Anti-oxidative effects of superoxide dismutase 3 on inflammatory diseases. J Mol Med (Berl) 2019; 98:59-69. [PMID: 31724066 DOI: 10.1007/s00109-019-01845-2] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 09/16/2019] [Accepted: 10/16/2019] [Indexed: 01/16/2023]
Abstract
Free radicals and other oxidants are critical determinants of the cellular signaling pathways involved in the pathogenesis of several human diseases including inflammatory diseases. Numerous studies have demonstrated the protective effects of antioxidant enzymes during inflammation by elimination of free radicals. The superoxide dismutase (SOD), an antioxidant enzyme, plays an essential pathogenic role in the inflammatory diseases by not only catalyzing the conversion of the superoxide to hydrogen peroxide and oxygen but also affecting immune responses. There are three distinct isoforms of SOD, which distribute in different cellular compartments such as cytosolic SOD1, mitochondrial SOD2, and extracellular SOD3. Many studies have investigated the anti-oxidative effects of SOD3 in the inflammatory diseases. Herein, in this review, we focus on the current understanding of SOD3 as a therapeutic protein in inflammatory diseases such as skin, autoimmune, lung, and cardiovascular inflammatory diseases. Moreover, the mechanism(s) by which SOD3 modulates immune responses and signal initiation in the pathogenesis of the diseases will be further discussed.
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Bjerg L, Hulman A, Carstensen B, Charles M, Witte DR, Jørgensen ME. Effect of duration and burden of microvascular complications on mortality rate in type 1 diabetes: an observational clinical cohort study. Diabetologia 2019; 62:633-643. [PMID: 30649599 DOI: 10.1007/s00125-019-4812-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Accepted: 12/17/2018] [Indexed: 10/27/2022]
Abstract
AIMS/HYPOTHESIS The role of burden and duration of multiple microvascular complications on mortality rate has not been explored in detail in type 1 diabetes. Taking complication burden and time-updated duration into account we aimed to quantify mortality rate in individuals with and without microvascular complications. METHODS This observational clinical cohort included 3828 individuals with type 1 diabetes attending the Steno Diabetes Center Copenhagen in 2001-2013. We used information on mortality and detailed clinical measures of microvascular complications from electronic patient records. Poisson models were used to model mortality rates according to complication burden. RESULTS During 26,665 person-years of follow-up, 503 deaths occurred. Compared with individuals without microvascular complications, the mortality rate ratio was 2.20 (95% CI 1.79, 2.69) for individuals with diabetic kidney disease, 1.72 (95% CI 1.39, 2.12) for individuals with neuropathy and 1.02 (95% CI 0.77, 1.37) for individuals with retinopathy, all adjusted for calendar time (year/month/day), age, duration of diabetes, sex, HbA1c, LDL-cholesterol, BMI, smoking status, systolic blood pressure, use of antihypertensive and lipid-lowering medication, and cardiovascular disease status. In individuals with two complications or more, the risk of mortality did not exceed the combined risk from each individual complication. Mortality rate ratios increased immediately after diagnosis of neuropathy and diabetic kidney disease. Mortality rate ratios were independent of the duration of neuropathy and retinopathy, while the mortality rate associated with diabetic kidney disease reached a stable level after approximately 3 years. CONCLUSIONS/INTERPRETATION Neuropathy and diabetic kidney disease are strong and independent risk markers of mortality in type 1 diabetes, whereas no evidence of higher mortality rate was found for retinopathy. We found no indication that the mortality risk with multiple complications exceeds the risk conferred by each complication separately. The duration spent with microvascular complications had only a marginal effect on mortality.
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Affiliation(s)
- Lasse Bjerg
- Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark.
- Section for General Medical Practice, Department of Public Health, Aarhus University, Bartholins Alle 2, 8000, Aarhus C, Denmark.
- Danish Diabetes Academy, Odense, Denmark.
| | - Adam Hulman
- Danish Diabetes Academy, Odense, Denmark
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Bendix Carstensen
- Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - Morten Charles
- Section for General Medical Practice, Department of Public Health, Aarhus University, Bartholins Alle 2, 8000, Aarhus C, Denmark
| | - Daniel R Witte
- Danish Diabetes Academy, Odense, Denmark
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Marit E Jørgensen
- Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark
- National Institute of Public Health, University of Southern Denmark, Odense, Denmark
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Campbell F, Lawton J, Rankin D, Clowes M, Coates E, Heller S, de Zoysa N, Elliott J, Breckenridge JP. Follow-Up Support for Effective type 1 Diabetes self-management (The FUSED Model): A systematic review and meta-ethnography of the barriers, facilitators and recommendations for sustaining self-management skills after attending a structured education programme. BMC Health Serv Res 2018; 18:898. [PMID: 30482202 PMCID: PMC6258400 DOI: 10.1186/s12913-018-3655-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 10/26/2018] [Indexed: 11/23/2022] Open
Abstract
Background People with type 1 diabetes who attend structured education training in self-management using flexible intensive therapy achieve improved blood glucose control and experience fewer episodes of severe hypoglycaemia. However, many struggle to sustain these improvements over time. To inform the design of more effective follow-up support we undertook a review of qualitative studies which have identified factors that influence and inform participants’ self-management behaviours after attending structured education and their need for support to sustain improvements in glycaemic control. Methods We undertook a meta-ethnography of relevant qualitative studies, identified using systematic search methods. Studies were included which focused on participants’ experiences of self-managing type 1 diabetes after attending structured education which incorporated training in flexible intensive insulin therapy. A line of argument approach was used to synthesise the findings. Results The search identified 18 papers from six studies. The studies included were judged to be of high methodological quality. The line of argument synthesis developed the Follow-Up Support for Effective type 1 Diabetes self-management (FUSED) model. This model outlines the challenges participants encounter in maintaining diabetes self-management practices after attending structured education, and describes how participants try to address these barriers by adapting, simplifying or personalising the self-management approaches they have learned. To help participants maintain the skills taught during courses, the FUSED model presents ten recommendations abstracted from the included papers to provide a logic model for a programme of individualised and responsive follow-up support. Conclusions This meta-ethnography highlights how providing skills training using structured education to people with type 1 diabetes does not necessarily result in participants adopting and sustaining recommended changes in behaviour. To help people sustain diabetes self-management skills after attending structured education, it is recommended that support be provided over the longer-term by appropriately trained healthcare professionals which is responsive to individuals’ needs. Although developed to inform support for people with type 1 diabetes, the FUSED model provides a framework that could also be applied to support individuals with other long term conditions which require complex self-management skills to be learned and sustained over time. Trial registration PROSPERO registration: CRD42017067961. Electronic supplementary material The online version of this article (10.1186/s12913-018-3655-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Fiona Campbell
- School of Health and Related Research (ScHARR), University of Sheffield, Regent Court, 30 Regent Street, S1 4DA, Sheffield, England.
| | - Julia Lawton
- The Usher Institute of Population Health Sciences and Informatics, Edinburgh Medical School of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland
| | - David Rankin
- The Usher Institute of Population Health Sciences and Informatics, Edinburgh Medical School of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland
| | - Mark Clowes
- School of Health and Related Research (ScHARR), University of Sheffield, Regent Court, 30 Regent Street, S1 4DA, Sheffield, England
| | - Elizabeth Coates
- School of Health and Related Research (ScHARR), University of Sheffield, Regent Court, 30 Regent Street, S1 4DA, Sheffield, England
| | - Simon Heller
- Sheffield University School of Medicine, Academic Unit of Diabetes, Endocrinology, and Metabolism, School of Medicine and Biomedical Sciences, Sheffield, UK
| | - Nicole de Zoysa
- Diabetes Centre, King's College Hospital, Denmark Hill, London, SE5 9RS, England
| | - Jackie Elliott
- Sheffield University School of Medicine, Academic Unit of Diabetes, Endocrinology, and Metabolism, School of Medicine and Biomedical Sciences, Sheffield, UK
| | - Jenna P Breckenridge
- School of Nursing and Health Sciences, University of Dundee, 11 Airlie Place, Dundee, DD1 4HJ, Scotland
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Bujang MA, Tiong XT, Saperi FE, Ismail M, Mustafa FI, Abd Hamid AM. The all-cause mortality and risk factors for mortality within five years among prevalent Type 1 Diabetes Mellitus Patients. Int J Diabetes Dev Ctries 2018. [DOI: 10.1007/s13410-018-0686-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
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Velho G, Ragot S, El Boustany R, Saulnier PJ, Fraty M, Mohammedi K, Fumeron F, Potier L, Marre M, Hadjadj S, Roussel R. Plasma copeptin, kidney disease, and risk for cardiovascular morbidity and mortality in two cohorts of type 2 diabetes. Cardiovasc Diabetol 2018; 17:110. [PMID: 30071874 PMCID: PMC6071392 DOI: 10.1186/s12933-018-0753-5] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 07/26/2018] [Indexed: 12/15/2022] Open
Abstract
Background Cardiovascular disease and kidney damage are tightly associated in people with type 2 diabetes. Experimental evidence supports a causal role for vasopressin (or antidiuretic hormone) in the development of diabetic kidney disease (DKD). Plasma copeptin, the COOH-terminal portion of pre-provasopressin and a surrogate marker of vasopressin, was shown to be positively associated with the development and progression of DKD. Here we assessed the association of plasma copeptin with the risk of cardiovascular events during follow-up in two prospective cohorts of type 2 diabetic patients, and we examined if this association could be mediated by deleterious effects of vasopressin on the kidney. Methods We studied 3098 and 1407 type 2 diabetic patients from the French cohorts DIABHYCAR and SURDIAGENE, respectively. We considered the incidence during follow-up (median: 5 years) of a combined end point composed of myocardial infarction, coronary revascularization, hospitalization for congestive heart failure, or cardiovascular death. Copeptin concentration was measured in baseline plasma samples by an immunoluminometric assay. Results The cumulative incidence of cardiovascular events during follow-up by sex-specific tertiles of baseline plasma copeptin was 15.6% (T1), 18.7% (T2) and 21.7% (T3) in DIABHYCAR (p = 0.002), and 27.7% (T1), 34.1% (T2) and 47.6% (T3) in SURDIAGENE (p < 0.0001). Cox proportional hazards survival regression analyses confirmed the association of copeptin with cardiovascular events in both cohorts: hazard ratio with 95% confidence interval for T3 vs. T1 was 1.29 (1.04–1.59), p = 0.02 (DIABHYCAR), and 1.58 (1.23–2.04), p = 0.0004 (SURDIAGENE), adjusted for sex, age, BMI, duration of diabetes, systolic blood pressure, arterial hypertension, HbA1c, total cholesterol, HDL-cholesterol, triglycerides, estimated glomerular filtration rate (eGFR), urinary albumin concentration (UAC), active tobacco smoking, and previous history of myocardial infarction at baseline. No interaction was observed between plasma copeptin and eGFR (p = 0.40) or UAC (p = 0.61) categories on the risk of cardiovascular events in analyses of pooled cohorts. Conclusions Plasma copeptin was positively associated with major cardiovascular events in people with type 2 diabetes. This association cannot be solely accounted for by the association of copeptin with kidney-related traits. Electronic supplementary material The online version of this article (10.1186/s12933-018-0753-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Gilberto Velho
- INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, Paris, 75006, France.
| | - Stéphanie Ragot
- INSERM, CIC 0802, Poitiers, France.,UFR de Médecine et Pharmacie, Université de Poitiers, Poitiers, France
| | - Ray El Boustany
- INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, Paris, 75006, France
| | - Pierre-Jean Saulnier
- INSERM, CIC 0802, Poitiers, France.,UFR de Médecine et Pharmacie, Université de Poitiers, Poitiers, France.,INSERM, Research Unit 1082, Poitiers, France
| | | | - Kamel Mohammedi
- Service d'Endocrinologie, Diabétologie, Nutrition, Hôpital Haut-Lévêque, Pessac, France.,Faculté de Médecine Paul Broca, Université de Bordeaux, Bordeaux, France
| | - Frédéric Fumeron
- INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, Paris, 75006, France.,Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France
| | - Louis Potier
- INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, Paris, 75006, France.,Department of Diabetology, Endocrinology and Nutrition, Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat Hospital, DHU FIRE, Paris, France.,Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France
| | - Michel Marre
- INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, Paris, 75006, France.,Department of Diabetology, Endocrinology and Nutrition, Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat Hospital, DHU FIRE, Paris, France.,Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France
| | - Samy Hadjadj
- INSERM, CIC 0802, Poitiers, France.,UFR de Médecine et Pharmacie, Université de Poitiers, Poitiers, France.,INSERM, Research Unit 1082, Poitiers, France.,Department of Endocrinology and Diabetology, Centre Hospitalier Universitaire de Poitiers, Poitiers, France
| | - Ronan Roussel
- INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, Paris, 75006, France.,Department of Diabetology, Endocrinology and Nutrition, Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat Hospital, DHU FIRE, Paris, France.,Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France
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Kellett J, Sampson M, Swords F, Murphy HR, Clark A, Howe A, Price C, Datta V, Myint KS. Young people's experiences of managing Type 1 diabetes at university: a national study of UK university students. Diabet Med 2018; 35:1063-1071. [PMID: 29687498 DOI: 10.1111/dme.13656] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/19/2018] [Indexed: 01/30/2023]
Abstract
AIM Little is known about the challenges of transitioning from school to university for young people with Type 1 diabetes. In a national survey, we investigated the impact of entering and attending university on diabetes self-care in students with Type 1 diabetes in all UK universities. METHODS Some 1865 current UK university students aged 18-24 years with Type 1 diabetes, were invited to complete a structured questionnaire. The association between demographic variables and diabetes variables was assessed using logistic regression models. RESULTS In total, 584 (31%) students from 64 hospitals and 37 university medical practices completed the questionnaire. Some 62% had maintained routine diabetes care with their home team, whereas 32% moved to the university provider. Since starting university, 63% reported harder diabetes management and 44% reported higher HbA1c levels than before university. At university, 52% had frequent hypoglycaemia, 9.6% reported one or more episodes of severe hypoglycaemia and 26% experienced diabetes-related hospital admissions. Female students and those who changed healthcare provider were approximately twice as likely to report poor glycaemic control, emergency hospital admissions and frequent hypoglycaemia. Females were more likely than males to report stress [odds ratio (OR) 4.78, 95% confidence interval (CI) 3.19-7.16], illness (OR 3.48, 95% CI 2.06-5.87) and weight management issues (OR 3.19, 95% CI 1.99-5.11) as barriers to self-care. Despite these difficulties, 91% of respondents never or rarely contacted university support services about their diabetes. CONCLUSION The study quantifies the high level of risk experienced by students with Type 1 diabetes during the transition to university, in particular, female students and those moving to a new university healthcare provider.
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Affiliation(s)
- J Kellett
- Norfolk and Norwich University Hospitals NHS Foundation Trust, Clinical Research and Trials Unit, Norwich, UK
| | - M Sampson
- Norfolk and Norwich University Hospitals NHS Foundation Trust, Clinical Research and Trials Unit, Norwich, UK
| | - F Swords
- Norfolk and Norwich University Hospitals NHS Foundation Trust, Clinical Research and Trials Unit, Norwich, UK
| | - H R Murphy
- University Medical Centre, University of East Anglia, Norwich, UK
| | - A Clark
- Norwich Medical School, Faculty of Health and Medical Sciences, Norwich, UK
| | - A Howe
- Norwich Medical School, Faculty of Health and Medical Sciences, Norwich, UK
| | - C Price
- University Medical Centre, University of East Anglia, Norwich, UK
| | - V Datta
- Department of Paediatrics, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
| | - K S Myint
- Department of Diabetes and Endocrinology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
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Monaco CMF, Hughes MC, Ramos SV, Varah NE, Lamberz C, Rahman FA, McGlory C, Tarnopolsky MA, Krause MP, Laham R, Hawke TJ, Perry CGR. Altered mitochondrial bioenergetics and ultrastructure in the skeletal muscle of young adults with type 1 diabetes. Diabetologia 2018; 61:1411-1423. [PMID: 29666899 DOI: 10.1007/s00125-018-4602-6] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 02/28/2018] [Indexed: 02/06/2023]
Abstract
AIMS/HYPOTHESIS A comprehensive assessment of skeletal muscle ultrastructure and mitochondrial bioenergetics has not been undertaken in individuals with type 1 diabetes. This study aimed to systematically assess skeletal muscle mitochondrial phenotype in young adults with type 1 diabetes. METHODS Physically active, young adults (men and women) with type 1 diabetes (HbA1c 63.0 ± 16.0 mmol/mol [7.9% ± 1.5%]) and without type 1 diabetes (control), matched for sex, age, BMI and level of physical activity, were recruited (n = 12/group) to undergo vastus lateralis muscle microbiopsies. Mitochondrial respiration (high-resolution respirometry), site-specific mitochondrial H2O2 emission and Ca2+ retention capacity (CRC) (spectrofluorometry) were assessed using permeabilised myofibre bundles. Electron microscopy and tomography were used to quantify mitochondrial content and investigate muscle ultrastructure. Skeletal muscle microvasculature was assessed by immunofluorescence. RESULTS Mitochondrial oxidative capacity was significantly lower in participants with type 1 diabetes vs the control group, specifically at Complex II of the electron transport chain, without differences in mitochondrial content between groups. Muscles of those with type 1 diabetes also exhibited increased mitochondrial H2O2 emission at Complex III and decreased CRC relative to control individuals. Electron tomography revealed an increase in the size and number of autophagic remnants in the muscles of participants with type 1 diabetes. Despite this, levels of the autophagic regulatory protein, phosphorylated AMP-activated protein kinase (p-AMPKαThr172), and its downstream targets, phosphorylated Unc-51 like autophagy activating kinase 1 (p-ULK1Ser555) and p62, was similar between groups. In addition, no differences in muscle capillary density or platelet aggregation were observed between the groups. CONCLUSIONS/INTERPRETATION Alterations in mitochondrial ultrastructure and bioenergetics are evident within the skeletal muscle of active young adults with type 1 diabetes. It is yet to be elucidated whether more rigorous exercise may help to prevent skeletal muscle metabolic deficiencies in both active and inactive individuals with type 1 diabetes.
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Affiliation(s)
- Cynthia M F Monaco
- Department of Pathology and Molecular Medicine, McMaster University, 4N65 Health Sciences Centre, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada
| | - Meghan C Hughes
- School of Kinesiology and Health Sciences, Muscle Health Research Centre, York University, Toronto, ON, Canada
| | - Sofhia V Ramos
- School of Kinesiology and Health Sciences, Muscle Health Research Centre, York University, Toronto, ON, Canada
| | - Nina E Varah
- Department of Pathology and Molecular Medicine, McMaster University, 4N65 Health Sciences Centre, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada
| | | | - Fasih A Rahman
- Department of Kinesiology, University of Windsor, Windsor, ON, Canada
| | - Chris McGlory
- Department of Kinesiology, McMaster University, Hamilton, ON, Canada
| | | | - Matthew P Krause
- Department of Kinesiology, University of Windsor, Windsor, ON, Canada
| | - Robert Laham
- School of Kinesiology and Health Sciences, Muscle Health Research Centre, York University, Toronto, ON, Canada
| | - Thomas J Hawke
- Department of Pathology and Molecular Medicine, McMaster University, 4N65 Health Sciences Centre, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada.
| | - Christopher G R Perry
- School of Kinesiology and Health Sciences, Muscle Health Research Centre, York University, Toronto, ON, Canada
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Garofolo M, Russo E, Miccoli R, Lucchesi D, Giusti L, Sancho-Bornez V, Daniele G, Del Prato S, Penno G. Albuminuric and non-albuminuric chronic kidney disease in type 1 diabetes: Association with major vascular outcomes risk and all-cause mortality. J Diabetes Complications 2018; 32:550-557. [PMID: 29705091 DOI: 10.1016/j.jdiacomp.2018.03.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 03/23/2018] [Accepted: 03/25/2018] [Indexed: 12/17/2022]
Abstract
AIMS Albuminuric and non-albuminuric phenotypes of chronic kidney disease (CKD) may have different cardiovascular risk and survival in type 1 diabetes (T1DM). Herein we estimated risk of major vascular outcomes by the EURODIAB PCS score and determined all-cause mortality rate in 774 T1DM according to CKD phenotypes. METHODS We evaluated the distribution of CKD phenotypes [no CKD, stages 1-2, non-albuminuric stage ≥3 (Alb-CKD), albuminuric stage ≥3 (Alb+CKD)], the EURODIAB risk score for major vascular outcomes [low- (LS), intermediate- (IS), and high- (HS) risk] and all-cause mortality over a follow-up of 8.25 ± 2.34 years. RESULTS Out of 774 subjects, 692 (89.4%) had no CKD, 53 (6.8%) CKD stages 1-2, 17 (2.2%) Alb-CKD and 12 (1.6%) Alb+CKD; 466 (60.2%) had LS, 205 (26.5%) IS and 103 (13.3%) HS. Distribution of HS was: no CKD, 9.1%; CKD stages 1-2, 34.0%; Alb-CKD, 64.7%; Alb+CKD, 91.7% (P < 0.0001). Mortality increased from no CKD, 3.0%; to stages 1-2, 15.1% (HR 4.504); Alb-CKD, 29.4% (8.573); Alb+CKD, 50.0% (20.683, P < 0.0001). Accounting for age and sex, HRs for mortality compared to no CKD were: CKD stages 1-2, 3.84 (P = 0.001); Alb-CKD, 2.97 (P = 0.046); Alb+CKD, 7.44 (P < 0.0001). Adjusting for sex and the EURODIAB score, HRs for mortality compared to no CKD were: CKD stages 1-2, 2.57 (P = 0.027); Alb-CKD, 2.77 (P = 0.058); Alb+CKD, 4.58 (P = 0.003). CONCLUSIONS In our T1DM cohort, one fifth of those with CKDs were non-albuminuric. This phenotype was associated with higher risk of major outcomes and similar rate of mortality as compared to CKD stages 1-2. The greatest risk and highest mortality occur in patients with Alb+CKD.
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Affiliation(s)
- Monia Garofolo
- Diabetes and Metabolic Disease Section, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 2 Via Paradisa, 56124 Pisa, Italy
| | - Eleonora Russo
- Diabetes and Metabolic Disease Section, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 2 Via Paradisa, 56124 Pisa, Italy
| | - Roberto Miccoli
- Diabetes and Metabolic Disease Section, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 2 Via Paradisa, 56124 Pisa, Italy
| | - Daniela Lucchesi
- Diabetes and Metabolic Disease Section, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 2 Via Paradisa, 56124 Pisa, Italy
| | - Laura Giusti
- Diabetes and Metabolic Disease Section, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 2 Via Paradisa, 56124 Pisa, Italy
| | - Veronica Sancho-Bornez
- Diabetes and Metabolic Disease Section, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 2 Via Paradisa, 56124 Pisa, Italy
| | - Giuseppe Daniele
- Diabetes and Metabolic Disease Section, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 2 Via Paradisa, 56124 Pisa, Italy
| | - Stefano Del Prato
- Diabetes and Metabolic Disease Section, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 2 Via Paradisa, 56124 Pisa, Italy.
| | - Giuseppe Penno
- Diabetes and Metabolic Disease Section, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 2 Via Paradisa, 56124 Pisa, Italy
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Knorr S, Juul S, Bytoft B, Lohse Z, Clausen TD, Jensen RB, Damm P, Beck-Nielsen H, Mathiesen ER, Jensen DM, Gravholt CH. Impact of type 1 diabetes on maternal long-term risk of hospitalisation and mortality: a nationwide combined clinical and register-based cohort study (The EPICOM study). Diabetologia 2018; 61:1071-1080. [PMID: 29478097 DOI: 10.1007/s00125-018-4575-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Accepted: 01/24/2018] [Indexed: 01/13/2023]
Abstract
AIMS/HYPOTHESIS The aims of this study were to examine long-term mortality and morbidity rates in mothers with type 1 diabetes, both overall and according to the level of albuminuria prior to pregnancy, the presence of hypertension, pre-eclampsia and periconceptional HbA1c. METHODS This study was a part of the EPICOM (Environmental Versus Genetic and Epigenetic Influences on Growth, Metabolism and Cognitive Function in Offspring of Mothers with Type 1 Diabetes) study, which is a prospective follow-up study focusing on pregnancies complicated by maternal type 1 diabetes. We carried out a nationwide combined clinical and register-based cohort study of mortality rates and hospital admissions in mothers with diabetes (n = 986) who gave birth between 1992 and 2000. Control mothers (n = 91,441) were women from the background population, matched according to age and year of childbirth. Age at follow-up was 32-66 years. RESULTS Mortality rate was increased threefold in mothers with diabetes compared with control mothers (HR 3.41 [95% CI 2.42, 4.81]; p < 0.0001), and was also increased with pre-gestational kidney dysfunction (normoalbuminuria, HR 2.17 [95% CI 1.28, 3.68]; microalbuminuria, HR 3.36 [95% CI 0.82, 13.8]; macroalbuminuria, HR 12.9 [95% CI 5.45, 30.7]). Moreover, the presence of hypertension prior to or at any time during pregnancy and of pre-eclampsia also increased mortality rate (hypertension, HR 4.34 [95% CI 2.13, 8.84]; pre-eclampsia, HR 5.55 [95% CI 2.71, 11.4]). Mortality rate also increased with higher levels of HbA1c in early pregnancy (HbA1c ≤75 mmol/mol [≤9%], HR 2.15 [95% CI 1.31, 3.53]; HbA1c >75 mmol/mol [>9%], HR 6.10 [95% CI 2.67, 14.0]). However, in mothers with diabetes and HbA1c <64 mmol/mol (<8%) in the first trimester and normal pre-gestational urinary albumin excretion rate (n = 517), mortality rate was comparable with that of control mothers. Among mothers with diabetes, mortality rate was associated with HbA1c level: per 11 mmol/mol (1 percentage point) increase in HbA1c, HR was 1.52 (95% CI 1.19, 1.94; p = 0.001). In mothers with diabetes, the overall incidence of hospital admissions was more than double (incidence rate ratio [IRR] 2.69 [95% CI 2.59, 2.80]; p < 0.0001) that of control mothers, as were admissions with various diagnoses from 14 out of 19 ICD-10 chapters. Among mothers with diabetes, the IRR for hospital admissions increased with the level of HbA1c: per 11 mmol/mol (1 percentage point) increase in HbA1c, HR was 1.07 (95% CI 1.04, 1.10; p < 0.0001). CONCLUSIONS/INTERPRETATION Overall, mothers with type 1 diabetes have a two- to threefold increase in mortality and morbidity rates. HbA1c levels, level of albuminuria around the time of conception, and the presence of hypertension and pre-eclampsia are important risk factors for mortality/morbidity in this cohort. However, it is reassuring that mothers with type 1 diabetes without kidney complications and with HbA1c <64 mmol/mol (<8%) in early pregnancy have a similar survival potential during the period where they are raising their children to that of control mothers from the background population.
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Affiliation(s)
- Sine Knorr
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark.
- Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
| | - Svend Juul
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Birgitte Bytoft
- Center for Pregnant Women with Diabetes, Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Zuzana Lohse
- Department of Endocrinology, Odense University Hospital, Odense, Denmark
| | - Tine D Clausen
- Department of Gynaecology and Obstetrics, Nordsjællands Hospital, Hillerød, Denmark
| | - Rikke B Jensen
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark
| | - Peter Damm
- Center for Pregnant Women with Diabetes, Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | - Elisabeth R Mathiesen
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Center for Pregnant Women with Diabetes, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark
| | - Dorte M Jensen
- Department of Endocrinology, Odense University Hospital, Odense, Denmark
| | - Claus H Gravholt
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark
- Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
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Diabetic Myopathy: current molecular understanding of this novel neuromuscular disorder. Curr Opin Neurol 2018; 30:545-552. [PMID: 28665810 DOI: 10.1097/wco.0000000000000479] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
PURPOSE OF REVIEW Here we summarize the evidence from human studies of the impairments to the structural, functional, and metabolic capacities in skeletal muscle in those with type 1 diabetes (T1D) - a condition known as diabetic myopathy. Given the importance of skeletal muscle for blood lipid and glucose management, the development and progression of diabetic myopathy would not only lead to increased insulin resistance, but also impact the ability to mitigate dysglycemic/dyslipidemic burdens. RECENT FINDINGS Despite the importance of skeletal muscle in whole-body metabolic control, studies investigating diabetic myopathy are startling limited. Recent findings have demonstrated that those with T1D exhibit decreased force production, increased fatigability, loss of muscle stem cells, and a greater reliance on glycolytic metabolism, as a result of reduced mitochondrial capacity. SUMMARY We propose a mechanistic model for the development of diabetic myopathy based on the human findings to date. This model suggests that repeated insulin injections in those with T1D leads to recurrent periods of intracellular hyperglycemia in myofibers. Resultant reductions in mitochondrial function lead to greater reliance on glycolytic metabolism and a concomitant shift in fiber type composition. Studies defining the scope and magnitude of diabetic myopathy and testing the veracity of this model are urgently needed in order to develop appropriate therapeutic strategies to maximize muscle health in those with T1D.
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Ritsinger V, Hero C, Svensson AM, Saleh N, Lagerqvist B, Eeg-Olofsson K, Norhammar A. Characteristics and Prognosis in Women and Men With Type 1 Diabetes Undergoing Coronary Angiography: A Nationwide Registry Report. Diabetes Care 2018; 41:876-883. [PMID: 29463579 DOI: 10.2337/dc17-2352] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 01/10/2018] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To describe sex aspects on extent of coronary artery disease (CAD) and prognosis in a contemporary population with type 1 diabetes. RESEARCH DESIGN AND METHODS All patients undergoing coronary angiography, 2001-2013, included in the Swedish Coronary Angiography and Angioplasty Registry and the Swedish National Diabetes Register as type 1 diabetes were followed for mortality until 31 December 2013. The coronary angiogram was classified into normal, one-vessel disease, two-vessel disease, three-vessel disease, and left main stem disease. RESULTS In all, 2,776 patients (42% women) with mean age 58 years (SD 11) were followed for 7.2 years (SD 2.2). Diabetes duration was longer in women (37 ± 14 vs. 34 ± 14 years in men; P < 0.001), who also had more retinopathy (68% vs. 65%; P = 0.050), whereas microalbuminuria was less common (41% vs. 51%; P < 0.001). Indications for coronary angiography did not substantially differ in women and men. The extent of CAD was somewhat less severe in women (normal angiogram 23.5% vs. 19.1%, three-vessel and left main stem disease 34.5% vs. 40.4%; P = 0.002), whereas mortality did not differ (adjusted hazard ratio 1.03 [95% CI 0.88-1.20]; P = 0.754). The standard mortality ratio for women the first year was 7.49 (5.73-9.62) and for men was 4.58 (3.60-5.74). CONCLUSIONS In patients with type 1 diabetes admitted for coronary angiography, the extent of CAD was almost similar in women and men, and total long-term mortality did not differ. Type 1 diabetes was associated with higher mortality risk in women than in men when compared with the general population. These data support that type 1 diabetes attenuates the cardiovascular risk difference seen in men and women in the general population.
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Affiliation(s)
- Viveca Ritsinger
- Cardiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden .,Department of Research and Development, Region Kronoberg, Växjö, Sweden
| | - Christel Hero
- Department of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
| | - Ann-Marie Svensson
- National Diabetes Register, Centre of Registers, Region Västra Götaland, Gothenburg, Sweden
| | - Nawzad Saleh
- Cardiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden
| | - Bo Lagerqvist
- Department of Cardiology, Uppsala University Hospital, Uppsala, Sweden
| | - Katarina Eeg-Olofsson
- Department of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
| | - Anna Norhammar
- Cardiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.,Capio S:t Göran's Hospital, Stockholm, Sweden
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Cockcroft EJ, Moudiotis C, Kitchen J, Bond B, Williams CA, Barker AR. High-intensity interval exercise and glycemic control in adolescents with type one diabetes mellitus: a case study. Physiol Rep 2018; 5:5/13/e13339. [PMID: 28684638 PMCID: PMC5506526 DOI: 10.14814/phy2.13339] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Revised: 05/26/2017] [Accepted: 06/04/2017] [Indexed: 01/12/2023] Open
Abstract
Current physical activity guidelines for youth with type 1 diabetes (T1D) are poorly supported by empirical evidence and the optimal dose of physical activity to improve glycemic control is unknown. This case report documents the effect of acute high‐intensity interval exercise (HIIE) and moderate‐intensity exercise (MIE) on 24‐h glycemic control in three adolescents with T1D using continuous glucose monitoring. Results highlight varied individual response to exercise across the participants. In two participants both MIE and HIIE resulted in a drop in blood glucose during exercise (−38 to −42% for MIE and −21–46% in HIIE) and in one participant both MIE and HIIE resulted in increased blood glucose (+19% and + 36%, respectively). Over the 24‐h period average blood glucose was lower for all participants in the HIIE condition, and for two for the MIE condition, compared to no exercise. All three participants reported HIIE to be more enjoyable than MIE. These data show both HIIE and MIE have the potential to improve short‐term glycemic control in youth with T1D but HIIE was more enjoyable. Future work with a larger sample size is required to explore the potential for HIIE to improve health markers in youth with T1D.
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Affiliation(s)
- Emma J Cockcroft
- Children's Health and Exercise Research Centre, Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, Exeter, UK
| | | | - Julie Kitchen
- Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Bert Bond
- Children's Health and Exercise Research Centre, Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, Exeter, UK
| | - Craig A Williams
- Children's Health and Exercise Research Centre, Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, Exeter, UK
| | - Alan R Barker
- Children's Health and Exercise Research Centre, Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, Exeter, UK
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50
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Gavurová B, Kubák M, Šoltés M, Barták M, Vagašová T. Time Trend, Age and Sex Distribution of Deceased from Diabetes Mellitus at the Regional Level in the Slovak Republic. Cent Eur J Public Health 2018. [PMID: 29524372 DOI: 10.21101/cejph.a5052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
AIM To describe the time trends, age and sex distribution of death from diabetes mellitus (E10-E14) as a significant part of endocrine, nutritional and metabolic diseases (E00-E90), during 1996-2014 in the Slovak regions, and to estimate the influence of social characteristics on mortality. METHODS Secondary data on deaths during 1996-2014 were gathered from the National Health Information Center in the Slovak Republic. The total crude death rate per 100,000 of the standard Slovak population and age-standardized death rate per 100,000 of the standard European population were calculated by direct standardization. Multilevel logistic regression analysis was performed. RESULTS Deaths from diabetes mellitus account for 91.6% of deaths registered in the endocrine, nutritional and metabolic diseases Chapter. The age-standardized death rate per 100,000 of inhabitants decreased from 19.2 in 1996 to 15.3 in 2014 in the Slovak Republic, although a massive increase of up to 32.5 was reported in 1999. The highest age-standardized death rates per 100,000 inhabitants were typical for the Košice, Nitra and Trenčín regions. On the other hand, the lowest counts were recorded in the Bratislava region. Mortality from diabetes mellitus starts to be evident in the 45-49 year age-group in both sexes. The median age of death for women is lower in the 75-79 year age-group in comparison to men although the total crude death rate for men in lower age groups is higher. After age 80 the situation is reversed. The odds of dying due to endocrine, nutritional and metabolic diseases decreases by 0.4% each year. The odds of dying are lower by 17% and 12.3%, respectively, in the Žilina and Prešov regions compared to Bratislava region. Women have a higher probability of dying by 38% in contrast to men, and married couples by 16.7% than singles. Age is proved to be an insignificant factor. CONCLUSIONS In spite of the declining trend of mortality from diabetes mellitus, it is necessary to reduce the risk of its incidence by healthier food consumption and physical activity.
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Affiliation(s)
- Beáta Gavurová
- Faculty of Economics, Technical University of Košice, Košice, Slovak Republic
| | - Matúš Kubák
- Faculty of Economics, Technical University of Košice, Košice, Slovak Republic
| | - Michal Šoltés
- Faculty of Economics, Technical University of Košice, Košice, Slovak Republic
| | - Miroslav Barták
- Department of Addictology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Tatiana Vagašová
- Faculty of Economics, Technical University of Košice, Košice, Slovak Republic
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