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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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Fewkes JJ, Dordevic AL, Murray M, Williamson G, Kellow NJ. Association between endothelial function and skin advanced glycation end-products (AGEs) accumulation in a sample of predominantly young and healthy adults. Cardiovasc Diabetol 2024; 23:332. [PMID: 39251982 PMCID: PMC11386354 DOI: 10.1186/s12933-024-02428-3] [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: 07/21/2024] [Accepted: 08/31/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND In populations with chronic disease, skin autofluorescence (SAF), a measure of long-term fluorescent advanced glycation end-products (AGEs) accumulation in body tissues, has been associated with vascular endothelial function, measured using flow-mediated dilation (FMD). The primary aim of this study was to quantify the relationship between endothelial function and tissue accumulation of AGEs in adults from the general population to determine whether SAF could be used as a marker to predict early impairment of the endothelium. METHODS A cross-sectional study was conducted with 125 participants (median age: 28.5 y, IQR: 24.4-36.0; 54% women). Endothelial function was measured by fasting FMD. Skin AGEs were measured as SAF using an AGE Reader. Participant anthropometry, blood pressure, and blood biomarkers were also measured. Associations were evaluated using multivariable regression analysis and were adjusted for significant covariates. RESULTS FMD was inversely correlated with SAF (ρ = -0.50, P < 0.001) and chronological age (ρ = -0.51, P < 0.001). In the multivariable analysis, SAF, chronological age, and male sex were independently associated with reduced FMD (B [95% CI]; -2.60 [-4.40, -0.80]; -0.10 [-0.16, -0.03]; 1.40 [0.14, 2.67], respectively), with the multivariable model adjusted R2 = 0.31, P < 0.001. CONCLUSIONS Higher skin AGE levels, as measured by SAF, were associated with lower FMD values, in a predominantly young, healthy population. Additionally, older age and male participants exhibited significantly lower FMD values, corresponding with compromised endothelial function. These results suggest that SAF, a simple and inexpensive marker, could be used to predict endothelial impairment before the emergence of any structural artery pathophysiology or classic cardiovascular disease risk markers. TRIAL REGISTRATION The study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000821897) and concurrently entered into the WHO International Clinical Trials Registry Platform under the same ID number.
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Affiliation(s)
- Juanita J Fewkes
- Department of Nutrition, Dietetics and Food, Faculty of Medicine, Nursing and Health Sciences, Monash University, 264 Ferntree Gully Road, Notting Hill, 3168, Australia
- Victorian Heart Institute, Victoria Heart Hospital, 631 Blackburn Road, Clayton, VIC, 3168, Australia
| | - Aimee L Dordevic
- Department of Nutrition, Dietetics and Food, Faculty of Medicine, Nursing and Health Sciences, Monash University, 264 Ferntree Gully Road, Notting Hill, 3168, Australia
- Victorian Heart Institute, Victoria Heart Hospital, 631 Blackburn Road, Clayton, VIC, 3168, Australia
| | - Margaret Murray
- Department of Nutrition, Dietetics and Food, Faculty of Medicine, Nursing and Health Sciences, Monash University, 264 Ferntree Gully Road, Notting Hill, 3168, Australia
- School of Chemistry, Faculty of Science, Monash University, Clayton, VIC, 3800, Australia
| | - Gary Williamson
- Department of Nutrition, Dietetics and Food, Faculty of Medicine, Nursing and Health Sciences, Monash University, 264 Ferntree Gully Road, Notting Hill, 3168, Australia
- Victorian Heart Institute, Victoria Heart Hospital, 631 Blackburn Road, Clayton, VIC, 3168, Australia
| | - Nicole J Kellow
- Department of Nutrition, Dietetics and Food, Faculty of Medicine, Nursing and Health Sciences, Monash University, 264 Ferntree Gully Road, Notting Hill, 3168, Australia.
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia.
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Alanazi AH, Selim MS, Yendamuri MR, Zhang D, Narayanan SP, Somanath PR. The impact of diabetes mellitus on blood-tissue barrier regulation and vascular complications: Is the lung different from other organs? Tissue Barriers 2024:2386183. [PMID: 39072526 DOI: 10.1080/21688370.2024.2386183] [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: 04/03/2024] [Revised: 07/12/2024] [Accepted: 07/16/2024] [Indexed: 07/30/2024] Open
Abstract
Diabetes Mellitus presents a formidable challenge as one of the most prevalent and complex chronic diseases, exerting significant strain on both patients and the world economy. It is recognized as a common comorbidity among severely ill individuals, often leading to a myriad of micro- and macro-vascular complications. Despite extensive research dissecting the pathophysiology and molecular mechanisms underlying vascular complications of diabetes, relatively little attention has been paid to potential lung-related complications. This review aims to illuminate the impact of diabetes on prevalent respiratory diseases, including chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), tuberculosis (TB), pneumonia infections, and asthma, and compare the vascular complications with other vascular beds. Additionally, we explore the primary mechanistic pathways contributing to these complications, such as the expression modulation of blood-tissue-barrier proteins, resulting in increased paracellular and transcellular permeability, and compromised immune responses rendering diabetes patients more susceptible to infections. The activation of inflammatory pathways leading to cellular injury and hastening the onset of these respiratory complications is also discussed.
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Affiliation(s)
- Abdulaziz H Alanazi
- Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA, USA
- Charlie Norwood VA Medical Center, Augusta, GA, USA
- Department of Clinical Practice, College of Pharmacy, Northern Border University, Rafha, Saudi Arabia
| | - Mohamed S Selim
- Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA, USA
- Charlie Norwood VA Medical Center, Augusta, GA, USA
| | - Manyasreeprapti R Yendamuri
- Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA, USA
- Charlie Norwood VA Medical Center, Augusta, GA, USA
| | - Duo Zhang
- Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA, USA
- Charlie Norwood VA Medical Center, Augusta, GA, USA
| | - S Priya Narayanan
- Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA, USA
- Charlie Norwood VA Medical Center, Augusta, GA, USA
| | - Payaningal R Somanath
- Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA, USA
- Charlie Norwood VA Medical Center, Augusta, GA, USA
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Zhao N, Yu X, Zhu X, Song Y, Gao F, Yu B, Qu A. Diabetes Mellitus to Accelerated Atherosclerosis: Shared Cellular and Molecular Mechanisms in Glucose and Lipid Metabolism. J Cardiovasc Transl Res 2024; 17:133-152. [PMID: 38091232 DOI: 10.1007/s12265-023-10470-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 11/23/2023] [Indexed: 02/28/2024]
Abstract
Diabetes is one of the critical independent risk factors for the progression of cardiovascular disease, and the underlying mechanism regarding this association remains poorly understood. Hence, it is urgent to decipher the fundamental pathophysiology and consequently provide new insights into the identification of innovative therapeutic targets for diabetic atherosclerosis. It is now appreciated that different cell types are heavily involved in the progress of diabetic atherosclerosis, including endothelial cells, macrophages, vascular smooth muscle cells, dependence on altered metabolic pathways, intracellular lipids, and high glucose. Additionally, extensive studies have elucidated that diabetes accelerates the odds of atherosclerosis with the explanation that these two chronic disorders share some common mechanisms, such as endothelial dysfunction and inflammation. In this review, we initially summarize the current research and proposed mechanisms and then highlight the role of these three cell types in diabetes-accelerated atherosclerosis and finally establish the mechanism pinpointing the relationship between diabetes and atherosclerosis.
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Affiliation(s)
- Nan Zhao
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, 10 You'anmen Outer West 1st Street, Beijing, 100069, China
| | - Xiaoting Yu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, 10 You'anmen Outer West 1st Street, Beijing, 100069, China
| | - Xinxin Zhu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, 10 You'anmen Outer West 1st Street, Beijing, 100069, China
| | - Yanting Song
- Department of Pathology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, 100029, China
| | - Fei Gao
- Department of Cardiology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, 100029, China
| | - Baoqi Yu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, 10 You'anmen Outer West 1st Street, Beijing, 100069, China.
- Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, 100069, China.
| | - Aijuan Qu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, 10 You'anmen Outer West 1st Street, Beijing, 100069, China.
- Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, 100069, China.
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Hosseini MS, Razavi Z, Bahri RA, Ehsani AH, Firooz A, Aryanian Z, Ehsani A, Sadeghi Y. Is skin autofluorescence a novel non-invasive marker in diabetes? A systematic review and meta-analysis of case-control studies. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2023; 28:68. [PMID: 38116483 PMCID: PMC10729688 DOI: 10.4103/jrms.jrms_127_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 05/25/2023] [Accepted: 07/04/2023] [Indexed: 12/21/2023]
Abstract
Background The advanced glycation end product (AGE) is produced from the nonenzymatic reaction between glucose and macromolecules by aging. Accumulation of AGE causes functional and structural changes in body proteins that lead to impairment of tissue protein functions. We aimed to validate AGE measurement by skin autofluorescence (SAF) in diabetes mellitus (DM) compared to the nondiabetes population. Materials and Methods We searched the PubMed, Cochrane, and Scopus databases from their inception till September 18, 2022, for casecontrol studies measuring AGE by SAF. Nonhuman studies, as well as review articles, study proposals, editorials, case reports, or congress posters, were excluded. We used a random effects model to assess the standard mean difference (MD) of age, body mass index (BMI), HbA1c, and SAF between diabetes and nondiabetes individuals. Results Higher SAF in DM patients indicated more accumulation of AGE compared with the nondiabetic population. Furthermore, HbA1c was considerably higher in DM patients. The MD of age, male gender, and BMI were significantly different between the DM individuals, compared with nondiabetic subjects, which can lead to altered SAF level and AGE production. There was a remarkable heterogeneity between diabetes and nondiabetes when measuring age, gender, and BMI, as well as HbA1c and SAF level. Conclusion This study could not confirm the validity of SAF as a surrogate marker in diabetes patients. Interestingly, metabolic load and high BMI can increase SAF, considerably. Altogether, SAF could be helpful in the future as a marker for metabolic syndrome or diabetes.
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Affiliation(s)
- Mahboobeh Sadat Hosseini
- Health Research Center, Lifestyle Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Zahra Razavi
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Razman Arabzadeh Bahri
- Medical Students, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Houshang Ehsani
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Firooz
- Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran
| | - Zeinab Aryanian
- Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Dermatology, Babol University of Medical Sciences, Babol, Iran
| | - Ala Ehsani
- Medical Students, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Yasaman Sadeghi
- Health Research Center, Lifestyle Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
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Bansal S, Burman A, Tripathi AK. Advanced glycation end products: Key mediator and therapeutic target of cardiovascular complications in diabetes. World J Diabetes 2023; 14:1146-1162. [PMID: 37664478 PMCID: PMC10473940 DOI: 10.4239/wjd.v14.i8.1146] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 03/21/2023] [Accepted: 05/22/2023] [Indexed: 08/11/2023] Open
Abstract
The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns. Cardiovascular complications associated with diabetes are the leading cause of morbidity and mortality. The cardiovascular diseases that accompany diabetes include angina, myocardial infarction, stroke, peripheral artery disease, and congestive heart failure. Among the various risk factors generated secondary to hyperglycemic situations, advanced glycation end products (AGEs) are one of the important targets for future diagnosis and prevention of diabetes. In the last decade, AGEs have drawn a lot of attention due to their involvement in diabetic patho-physiology. AGEs can be derived exogenously and endogenously through various pathways. These are a non-homogeneous, chemically diverse group of compounds formed non-enzymatically by condensation between carbonyl groups of reducing sugars and free amino groups of protein, lipids, and nucleic acid. AGEs mediate their pathological effects at the cellular and extracellular levels by multiple pathways. At the cellular level, they activate signaling cascades via the receptor for AGEs and initiate a complex series of intracellular signaling resulting in reactive oxygen species generation, inflammation, cellular proliferation, and fibrosis that may possibly exacerbate the damaging effects on cardiac functions in diabetics. AGEs also cause covalent modifications and cross-linking of serum and extracellular matrix proteins; altering their structure, stability, and functions. Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities. In the present review, we recapitulate the role of AGEs as a crucial mediator of hyperglycemia-mediated detrimental effects in diabetes-associated complications. Furthermore, this review presents an overview of future perspectives for new therapeutic interventions to ameliorate cardiovascular complications in diabetes.
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Affiliation(s)
- Savita Bansal
- Department of Biochemistry, Institute of Home Sciences, University of Delhi, New Delhi 110016, India
| | - Archana Burman
- Department of Biochemistry, Institute of Home Economics, University of Delhi, New Delhi 110016, India
| | - Asok Kumar Tripathi
- Department of Biochemistry, University College of Medical Sciences, University of Delhi, New Delhi 110095, India
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Aoki E, Hirashima T, Kumamoto Y, Yamamoto Y, Suzuki N, Oshima T, Saito D, Hirano T. Clinical significance of skin autofluorescence for diabetic macroangiopathy and comparison with conventional markers of atherosclerosis: a cross-sectional and prospective study. Diabetol Int 2023; 14:145-154. [PMID: 37090128 PMCID: PMC10113414 DOI: 10.1007/s13340-022-00608-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 11/11/2022] [Indexed: 11/29/2022]
Abstract
Background Skin autofluorescence (SAF) is a marker for the accumulation of advanced glycation end products (AGEs), and is associated with diabetic macroangiopathy. However, whether SAF is superior to conventional markers of atherosclerosis such as carotid intima-media thickness (IMT) and pulse wave velocity (PWV) in detecting macroangiopathy remains unclear. Methods We recruited 845 patients with type 2 diabetes enrolled in a community diabetes cohort (ViNA cohort) who had SAF, IMT, and PWV measured at baseline. The prevalence of macroangiopathy at baseline and new cardiovascular events during the 2-year follow-up period was investigated. SAF was measured using an AGE reader. Coronary artery calcification (CAC) was measured by computed tomography in 485 patients. Peripheral artery disease (PAD) was defined as the ankle-brachial blood pressure ratio of ≤ 0.9. Results SAF, IMT, and PWV were significantly correlated with each other, and age, diabetes duration, and estimated glomerular filtration rate were their strong confounders. SAF was associated with baseline stroke and new stroke after adjusting for confounders, but not with coronary artery disease (CAD) or PAD. The nonsignificant relationship between SAF and CAD was consistent with the relationship between SAF and CAC. Multivariate analysis showed a significant association of SAF with baseline and new stroke independent of IMT and PWV. Maximum-IMT was significantly associated with baseline CAD, PAD, and stroke, but not with a new stroke, whereas PWV was associated with a new stroke. Conclusion Among diabetic macroangiopathies, SAF is a good stroke biomarker, but not for CAD and PAD. Supplementary Information The online version contains supplementary material available at 10.1007/s13340-022-00608-8.
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Affiliation(s)
- Ema Aoki
- Diabetes Center, Ebina General Hospital, Kawaharaguchi 1320, Ebina, Kanagawa 243-0433 Japan
| | - Takeshi Hirashima
- Diabetes Center, Ebina General Hospital, Kawaharaguchi 1320, Ebina, Kanagawa 243-0433 Japan
| | - Yuko Kumamoto
- Department of Clinical Laboratory, Ebina General Hospital, Ebina, Japan
| | - Yuko Yamamoto
- Department of Clinical Laboratory, Ebina General Hospital, Ebina, Japan
| | - Natsuko Suzuki
- Diabetes Center, Ebina General Hospital, Kawaharaguchi 1320, Ebina, Kanagawa 243-0433 Japan
| | - Taito Oshima
- Diabetes Center, Ebina General Hospital, Kawaharaguchi 1320, Ebina, Kanagawa 243-0433 Japan
| | - Daizo Saito
- Department of Nutrition, Ebina General Hospital, Ebina, Japan
| | - Tsutomu Hirano
- Diabetes Center, Ebina General Hospital, Kawaharaguchi 1320, Ebina, Kanagawa 243-0433 Japan
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Zhu J, Lian S, Zhong H, Sun R, Xiao Z, Li H. Detection of Advanced Glycosylation End Products in the Cornea Based on Molecular Fluorescence and Machine Learning. BIOSENSORS 2023; 13:170. [PMID: 36831936 PMCID: PMC9953900 DOI: 10.3390/bios13020170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 01/02/2023] [Accepted: 01/17/2023] [Indexed: 06/18/2023]
Abstract
Advanced glycosylation end products (AGEs) are continuously produced and accumulated in the bodies of diabetic patients. To effectively predict disease trends in diabetic patients, a corneal fluorescence detection device was designed based on the autofluorescence properties of AGEs, and corneal fluorescence measurements were performed on 83 volunteers. Multiple linear regression (MLR), extreme gradient boosting (XGBoost), support vector regression (SVR), and back-propagation neural network (BPNN) were used to predict the human AGE content. Physiological parameters which may affect corneal AGE content were collected for a correlation analysis to select the features that had a strong correlation with the corneal concentration of AGEs to participate in modeling. By comparing the predictive effects of the four models in the two cases of a single-input feature and a multi-input feature, it was found that the model with the single-input feature had a better predictive effect. In this case, corneal AGE content was predicted by a single-input SVR model, with the average error rate (AER), mean square error (MSE), and determination coefficient R-squared (R2) of the SVR model calculated as 2.43%, 0.026, and 0.932, respectively. These results proved the potential of our method and device for noninvasive detection of the concentration of AGEs in the cornea.
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Affiliation(s)
- Jianming Zhu
- School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin 541004, China
- Guangxi Key Laboratory of Automatic Detecting Technology and Instruments, Guilin University of Electronic Technology, Guilin 541004, China
| | - Sifeng Lian
- School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin 541004, China
| | - Haochen Zhong
- School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin 541004, China
| | - Ruiyang Sun
- School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin 541004, China
| | - Zhenbang Xiao
- School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin 541004, China
| | - Hua Li
- School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin 541004, China
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Lee J, Yun JS, Ko SH. Advanced Glycation End Products and Their Effect on Vascular Complications in Type 2 Diabetes Mellitus. Nutrients 2022; 14:3086. [PMID: 35956261 PMCID: PMC9370094 DOI: 10.3390/nu14153086] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 07/22/2022] [Accepted: 07/26/2022] [Indexed: 11/16/2022] Open
Abstract
Diabetes is well established as a chronic disease with a high health burden due to mortality or morbidity from the final outcomes of vascular complications. An increased duration of hyperglycemia is associated with abnormal metabolism. Advanced glycation end products (AGEs) are nonenzymatic glycated forms of free amino acids that lead to abnormal crosslinking of extra-cellular and intracellular proteins by disrupting the normal structure. Furthermore, the interaction of AGEs and their receptors induces several pathways by promoting oxidative stress and inflammation. In this review, we discuss the role of AGEs in diabetic vascular complications, especially type 2 DM, based on recent clinical studies.
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Affiliation(s)
- Jeongmin Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03391, Korea;
| | - Jae-Seung Yun
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Korea;
| | - Seung-Hyun Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Korea;
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Advanced Glycations End Products in the Skin as Biomarkers of Cardiovascular Risk in Type 2 Diabetes. Int J Mol Sci 2022; 23:ijms23116234. [PMID: 35682915 PMCID: PMC9181586 DOI: 10.3390/ijms23116234] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 05/31/2022] [Accepted: 05/31/2022] [Indexed: 02/01/2023] Open
Abstract
The incidence and prevalence of diabetes are increasing worldwide, and cardiovascular disease (CVD) is the leading cause of death among subjects with type 2 diabetes (T2D). The assessment and stratification of cardiovascular risk in subjects with T2D is a challenge. Advanced glycation end products are heterogeneous molecules produced by non-enzymatic glycation of proteins, lipids, or nucleic acids. Accumulation of advanced glycation end products is increased in subjects with T2D and is considered to be one of the major pathogenic mechanism in developing complications in diabetes. Skin AGEs could be assessed by skin autofluorescence. This method has been validated and related to the presence of micro and macroangiopathy in individuals with type 2 diabetes. In this context, the aim of this review is to critically summarize current knowledge and scientific evidence on the relationship between skin AGEs and CVD in subjects with type 2 diabetes, with a brief reference to other diabetes-related complications.
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Legiawati L, Bramono K, Indriatmi W, Yunir E, Pratama AI. Type 2 Diabetes Mellitus with Early Dry Skin Disorder: A Comparison Study Between Primary and Tertiary Care in Indonesia. Curr Diabetes Rev 2022; 18:e060821195350. [PMID: 34365924 DOI: 10.2174/1573399817666210806102212] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 01/29/2021] [Accepted: 02/13/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND The prevalence of Type 2 Diabetes Mellitus (T2DM) in Indonesia has continued to increase over the years. Management of T2DM is challenging across clinical settings, including primary and tertiary care. Uncontrolled T2DM puts patients at risk of the development of T2DM complications, especially early-stage dry skin that is neglected by most of the patients. This study aimed to investigate the comparison between the T2DM management profile and dry skin clinical profile of T2DM patients in primary care and tertiary care settings. METHODS The study was conducted as a cross-sectional epidemiological study by comparing T2DM patient profiles in primary and tertiary care. The data collected included sociodemographic, clinical, and laboratory data that were correlated with T2DM and early dry skin related-T2DM. This study included early dry skin within the SRRC score of 3-11 and excluded infection, ulcer, and severe erythema. RESULTS The patients in primary and tertiary care presented poorly controlled T2DM with median HbA1c levels of 7.8% and 7.6%. The patients in primary care also presented with high triglyceride, 179 mg/dl. Furthermore, several significant differences were found in the duration of T2DM, duration of dry skin, and DM treatment (OAD and insulin). CONCLUSION Significant differences in the duration of T2DM, duration of dry skin, and DM treatment (OAD and insulin) might be affected by the parameter of T2DM glycemic control (Blood pressure (BP), body mass index (BMI), HbA1c, random blood glucose (RBG), and triglyceride).
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Affiliation(s)
- Lili Legiawati
- Department of Dermatology and Venereology, Faculty of Medicine Universitas Indonesia - Dr. Cipto Mangunkusumo National Central General Hospital, Jl Salemba Raya No. 6, Central Jakarta 10430, Indonesia
| | - Kusmarinah Bramono
- Department of Dermatology and Venereology, Faculty of Medicine Universitas Indonesia - Dr. Cipto Mangunkusumo National Central General Hospital, Jl Salemba Raya No. 6, Central Jakarta 10430, Indonesia
| | - Wresti Indriatmi
- Department of Dermatology and Venereology, Faculty of Medicine Universitas Indonesia - Dr. Cipto Mangunkusumo National Central General Hospital, Jl Salemba Raya No. 6, Central Jakarta 10430, Indonesia
| | - Em Yunir
- Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Dr. Cipto Mangunkusumo National Central General Hospital, Jl Salemba Raya No. 6, Central Jakarta 10430, Indonesia
| | - Aditya Indra Pratama
- Department of Dermatology and Venereology, Faculty of Medicine Universitas Indonesia - Dr. Cipto Mangunkusumo National Central General Hospital, Jl Salemba Raya No. 6, Central Jakarta 10430, Indonesia
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Corica D, Pepe G, Currò M, Aversa T, Tropeano A, Ientile R, Wasniewska M. Methods to investigate advanced glycation end-product and their application in clinical practice. Methods 2021; 203:90-102. [DOI: 10.1016/j.ymeth.2021.12.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2020] [Revised: 12/01/2021] [Accepted: 12/16/2021] [Indexed: 12/15/2022] Open
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Grahovac M, Kumric M, Vilovic M, Martinovic D, Kreso A, Ticinovic Kurir T, Vrdoljak J, Prizmic K, Božić J. Adherence to Mediterranean diet and advanced glycation endproducts in patients with diabetes. World J Diabetes 2021; 12:1942-1956. [PMID: 34888018 PMCID: PMC8613665 DOI: 10.4239/wjd.v12.i11.1942] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 07/01/2021] [Accepted: 10/11/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In recent years, American Diabetes Association started to strongly advocate the Mediterranean diet (MD) over other diets in patients with diabetes mellitus (DM) because of its beneficial effects on glycemic control and cardiovascular (CV) risk factors. Tissue levels of advanced glycation endproducts (AGEs) emerged as an indicator of CV risk in DM. Skin biopsy being invasive, the use of AGE Reader has been shown to reflect tissue AGEs reliably.
AIM To examine the association between adherence to MD and AGEs in patients with DM type II.
METHODS This cross-sectional study was conducted on 273 patients with DM type II. A survey questionnaire was composed of 3 separate sections. The first part of the questionnaire included general data and the habits of the participants. The second part aimed to assess the basic parameters of participants’ diseases and associated conditions. The third part of the questionnaire was the Croatian version of the 14-item MD service score (MDSS). AGEs levels and associated CV risk were measured using AGE Reader (DiagnOptics Technologies BV, Groningen, The Netherlands).
RESULTS A total of 27 (9.9%) patients fulfilled criteria for adherence to MD, with a median score of 8.0 (6.0-10.0). Patients with none/limited CV risk had significantly higher percentage of MD adherence in comparison to patients with increased/definite CV risk (15.2% vs 6.9%, P = 0.028), as well as better adherence to guidelines for nuts (23.2% vs 12.6%, P = 0.023) and legumes (40.4% vs 25.9%, P = 0.013) consumption. Higher number of patients with glycated hemoglobin (HbA1c) < 7% adhered to MD when compared to patients with HbA1c > 7% (14.9% vs 7.3%, P = 0.045). Moreover, those patients followed the MDSS guidelines for eggs (33.0% vs 46.8%, P = 0.025) and wine (15.6% vs 29.8%, P = 0.006) consumption more frequently. MDSS score had significant positive correlation with disease duration (r = 0.179, P = 0.003) and negative correlation with body mass index (BMI) values (r = -0.159, P = 0.008). In the multiple linear regression model, BMI (β ± SE, -0.09 ± 0.04, P = 0.037) and disease duration (β ± SE, 0.07 ± 0.02, P < 0.001) remained significant independent correlates of the MDSS score. Patients with HbA1c > 7% think that educational programs on nutrition would be useful for patients in significantly more cases than patients with HbA1c < 7% (98.9% vs 92.6%, P = 0.009).
CONCLUSION Although adherence to MD was very low among people with diabetes, we demonstrated that adherence to MD is greater in patients with lower CV risk, longer disease duration, and well-controlled glycaemia.
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Affiliation(s)
- Marko Grahovac
- Department of Pharmacology, University of Split School of Medicine, Split 21000, Croatia
| | - Marko Kumric
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
| | - Marino Vilovic
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
| | - Dinko Martinovic
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
| | - Ante Kreso
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
| | - Tina Ticinovic Kurir
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
- Department of Endocrinology, University Hospital of Split, Split 21000, Croatia
| | - Josip Vrdoljak
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
| | - Karlo Prizmic
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
| | - Joško Božić
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
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Planas A, Simó-Servat O, Bañeras J, Sánchez M, García E, Ortiz ÁM, Ruiz-Meana M, Hernández C, Ferreira-González I, Simó R. Usefulness of skin advanced glycation end products to predict coronary artery calcium score in patients with type 2 diabetes. Acta Diabetol 2021; 58:1403-1412. [PMID: 34032928 DOI: 10.1007/s00592-021-01735-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 05/04/2021] [Indexed: 01/02/2023]
Abstract
AIM The early identification of type 2 diabetic (T2D) patients at risk of developing coronary artery disease (CAD) remains a challenge. The coronary artery calcium score (CACs) is considered the most sensitive tool for assessing CAD risk in diabetic population, and the identification of a more targeted population in which the CACs would be more cost-efficient seems warranted. The accumulation of advanced glycation end products plays an important role in the pathogenesis of cardiovascular disease (CVD) in patients with diabetes. The aim of this study was to evaluate whether the assessment of skin autofluorescence (SAF) could be useful tool to identify those diabetic patients in whom CACs assessment should be prioritized. METHODS Prospective case-control study, comprising 156 subjects with T2D with no history of clinical CVD and 52 non-diabetic subjects matched by age. A value of CACs ≥ 400 Agatston Units (AU) was considered as "high CVD risk." Logistic regression analysis to predict a CACs ≥ 400 AU was performed. Sensibility and specificity were calculated using the optimal cutoff point based on ROC curve. RESULTS T2D patients had higher value of SAF compared to controls (p = 0.011). Among subjects with diabetes, 122 presented CACs < 400 AU and 35 CACs ≥ 400 AU. SAF values were significantly higher among the group with CACs ≥ 400AU compared to patients with CACs < 400 (2.96 ± 0.86 vs. 2.59 ± 0.57; p = 0.0035). The logistic regression analysis showed that age, HDL-cholesterol and SAF values were independently related to CACs ≥ 400UA. CONCLUSION Our finding suggests that SAF could be useful in selecting T2D patients in whom the screening for CAD by means of CACs assessment would be more cost-effective.
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Affiliation(s)
- Alejandra Planas
- Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Autonomous University of Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain
- CIBER en Diabetes y Enfermedades Metabólicas (CIBERDEM), Spanish Institute of Health (ISCIII), Madrid, Spain
| | - Olga Simó-Servat
- Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Autonomous University of Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain
- CIBER en Diabetes y Enfermedades Metabólicas (CIBERDEM), Spanish Institute of Health (ISCIII), Madrid, Spain
| | - Jordi Bañeras
- Cardiology Department, Vall d'Hebron University Hospital and Research Institute, Autonomous University of Barcelona, Barcelona, Spain
- CIBER en Epidemiología y Salud Pública (CIBERESP), Spanish Institute of Health (ISCIII), Madrid, Spain
| | - Mónica Sánchez
- Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Autonomous University of Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain
| | - Esther García
- Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Autonomous University of Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain
| | - Ángel M Ortiz
- Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Autonomous University of Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain
- CIBER en Diabetes y Enfermedades Metabólicas (CIBERDEM), Spanish Institute of Health (ISCIII), Madrid, Spain
| | - Marisol Ruiz-Meana
- Cardiology Department, Vall d'Hebron University Hospital and Research Institute, Autonomous University of Barcelona, Barcelona, Spain
- CIBER-CV, Spanish Institute of Health (ISCIII), Madrid, Spain
| | - Cristina Hernández
- Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Autonomous University of Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain
- CIBER en Diabetes y Enfermedades Metabólicas (CIBERDEM), Spanish Institute of Health (ISCIII), Madrid, Spain
| | - Ignacio Ferreira-González
- Cardiology Department, Vall d'Hebron University Hospital and Research Institute, Autonomous University of Barcelona, Barcelona, Spain
- CIBER en Epidemiología y Salud Pública (CIBERESP), Spanish Institute of Health (ISCIII), Madrid, Spain
| | - Rafael Simó
- Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Autonomous University of Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain.
- CIBER en Diabetes y Enfermedades Metabólicas (CIBERDEM), Spanish Institute of Health (ISCIII), Madrid, Spain.
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Krasnodębski M, Grąt K, Morawski M, Borkowski J, Krawczyk P, Zhylko A, Skalski M, Kalinowski P, Zieniewicz K, Grąt M. Skin autofluorescence as a novel predictor of acute kidney injury after liver resection. World J Surg Oncol 2021; 19:276. [PMID: 34526025 PMCID: PMC8444415 DOI: 10.1186/s12957-021-02394-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 09/03/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Skin autofluorescence (SAF) reflects accumulation of advanced glycation end-products (AGEs). The aim of this study was to evaluate predictive usefulness of SAF measurement in prediction of acute kidney injury (AKI) after liver resection. METHODS This prospective observational study included 130 patients undergoing liver resection. The primary outcome measure was AKI. SAF was measured preoperatively and expressed in arbitrary units (AU). RESULTS AKI was observed in 32 of 130 patients (24.6%). SAF independently predicted AKI (p = 0.047), along with extent of resection (p = 0.019) and operative time (p = 0.046). Optimal cut-off for SAF in prediction of AKI was 2.7 AU (area under the curve [AUC] 0.611), with AKI rates of 38.7% and 20.2% in patients with high and low SAF, respectively (p = 0.037). Score based on 3 independent predictors (SAF, extent of resection, and operative time) well stratified the risk of AKI (AUC 0.756), with positive and negative predictive values of 59.3% and 84.0%, respectively. In particular, SAF predicted AKI in patients undergoing major and prolonged resections (p = 0.010, AUC 0.733) with positive and negative predictive values of 81.8%, and 62.5%, respectively. CONCLUSIONS AGEs accumulation negatively affects renal function in patients undergoing liver resection. SAF measurement may be used to predict AKI after liver resection, particularly in high-risk patients.
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Affiliation(s)
- Maciej Krasnodębski
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
| | - Karolina Grąt
- Second Department of Clinical Radiology, Medical University of Warsaw, Warsaw, Poland
| | - Marcin Morawski
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Jan Borkowski
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Piotr Krawczyk
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Andriy Zhylko
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Michał Skalski
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Piotr Kalinowski
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Krzysztof Zieniewicz
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Michał Grąt
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
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Rojubally S, Simoneau A, Monlun M, Foussard N, Blanco L, Domenge F, Mohammedi K, Ducasse E, Caradu C, Rigalleau V. For diabetic type 1 patients, the skin autofluorescence predicts ulcers and amputations. J Diabetes Complications 2021; 35:107808. [PMID: 33386214 DOI: 10.1016/j.jdiacomp.2020.107808] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 11/02/2020] [Accepted: 11/11/2020] [Indexed: 11/27/2022]
Abstract
We searched whether the accumulation of Advanced Glycation End-products (AGEs), reflected by the skin autofluorescence (SAF), could predict diabetic foot ulcers (DFUs) during the long-term follow-up of people with type 1 diabetes. During year 2009, we measured the SAF with an AGE-Reader in 206 subjects with type 1 diabetes. DFU and amputations were registered during the 10 following years. The relation between the SAF and later DFU was analyzed by Cox model regression, adjusted for vascular risk factors. The 206 participants were mainly men (55.8%), 51 ± 15 years old, with a 22 ± 13 years diabetes duration. Twelve subjects presented a DFU. Their SAF were higher: 2.61 ± 0.89 AU vs 2.11 ± 0.53 for the others (p = 0.003), related to the risk of DFU (OR:3.69; 95% CI: 1.06-12.79) after adjustment for age, gender, diabetes duration, initial HbA1c, arterial hypertension, history of smoking, blood lipids and use of a statin. Five subjects were amputated, also related to the initial SAF: OR: 11.28 (95% CI: 1.76-79.97) after adjustment for age, gender, duration of diabetes, and HbA1c. The SAF has already been related to diabetic neuropathy and peripheral arterial disease. It predicts DFU in type 1 diabetes, which suggests that AGEs play a role in this highly specific and feared complication.
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Affiliation(s)
- Saad Rojubally
- Bordeaux CHU and University, Endocrinology-Diabetology-Nutrition and Vascular Surgery, 33000 Bordeaux, France
| | - Amélie Simoneau
- Bordeaux CHU and University, Endocrinology-Diabetology-Nutrition and Vascular Surgery, 33000 Bordeaux, France
| | - Marie Monlun
- Bordeaux CHU and University, Endocrinology-Diabetology-Nutrition and Vascular Surgery, 33000 Bordeaux, France
| | - Ninon Foussard
- Bordeaux CHU and University, Endocrinology-Diabetology-Nutrition and Vascular Surgery, 33000 Bordeaux, France
| | - Laurence Blanco
- Bordeaux CHU and University, Endocrinology-Diabetology-Nutrition and Vascular Surgery, 33000 Bordeaux, France
| | - Frédéric Domenge
- Bordeaux CHU and University, Endocrinology-Diabetology-Nutrition and Vascular Surgery, 33000 Bordeaux, France
| | - Kamel Mohammedi
- Bordeaux CHU and University, Endocrinology-Diabetology-Nutrition and Vascular Surgery, 33000 Bordeaux, France
| | - Eric Ducasse
- Bordeaux CHU and University, Endocrinology-Diabetology-Nutrition and Vascular Surgery, 33000 Bordeaux, France
| | - Caroline Caradu
- Bordeaux CHU and University, Endocrinology-Diabetology-Nutrition and Vascular Surgery, 33000 Bordeaux, France
| | - Vincent Rigalleau
- Bordeaux CHU and University, Endocrinology-Diabetology-Nutrition and Vascular Surgery, 33000 Bordeaux, France.
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Sex May Modulate the Effects of Combined Polyphenol Extract and L-citrulline Supplementation on Ambulatory Blood Pressure in Adults with Prehypertension: A Randomized Controlled Trial. Nutrients 2021; 13:nu13020399. [PMID: 33513929 PMCID: PMC7912201 DOI: 10.3390/nu13020399] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 01/17/2021] [Accepted: 01/20/2021] [Indexed: 11/16/2022] Open
Abstract
Increased blood pressure (BP), vascular dysfunction and inflammation are involved in the etiology of cardiovascular disease (CVD). Although several dietary components such as polyphenols and L-citrulline may help to control BP, their combined impact on ambulatory BP in individuals at risk of CVD remains unknown. The objective of this research was to investigate the short-term impact of supplementation with a combination of polyphenol extract and L-citrulline on ambulatory BP, endothelial function and inflammation. In a randomized double-blind parallel trial, 73 men and women with prehypertension were supplemented with a placebo (cellulose, n = 34, Plac) or 548 mg/day of polyphenols and 2 g/day of L-citrulline (n = 35, Suppl) for 6 weeks. The primary outcome of this study was the difference between groups in 24-h ambulatory diastolic BP (DBP) at week six. Secondary outcomes were a difference between groups at week six in ambulatory systolic BP (SBP), casual BP, serum lipids and high-sensitivity C-reactive protein (hs-CRP) concentrations and skin advanced glycation end products (AGEs). Potential interaction of treatment with sex was examined. Suppl had no impact on mean ambulatory SBP and DBP (p > 0.10 vs. placebo). Daytime and 24-h SBP were reduced with Suppl in women (p ≤ 0.01), but not in men (p ≥ 0.27). A non-significant reduction in AGEs was observed after Suppl compared to Plac among all participants (p = 0.07) and there was no difference in the concentrations of blood lipids (p > 0.20) or CRP (p = 0.36) between treatments at week six. Therefore, supplementation with polyphenol extract and L-citrulline for 6 weeks has no impact on ambulatory BP, blood lipids and CRP in adults with prehypertension. However, the polyphenol extract/L-citrulline supplement may reduce ambulatory SBP in women, but not in men. These preliminary results need further research efforts towards further documenting this sex-dependent BP response to supplementation with polyphenols and L-citrulline.
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Omori K, Katakami N, Arakawa S, Yamamoto Y, Ninomiya H, Takahara M, Matsuoka TA, Tsugawa H, Furuno M, Bamba T, Fukusaki E, Shimomura I. Identification of Plasma Inositol and Indoxyl Sulfate as Novel Biomarker Candidates for Atherosclerosis in Patients with Type 2 Diabetes. -Findings from Metabolome Analysis Using GC/MS. J Atheroscler Thromb 2020; 27:1053-1067. [PMID: 31983701 PMCID: PMC7585911 DOI: 10.5551/jat.52506] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 12/08/2019] [Indexed: 12/29/2022] Open
Abstract
AIM An identification of the high-risk group of atherosclerotic cardiovascular disease (CVD) is important in the management of patients with diabetes. Metabolomics is a potential tool for the discovery of new biomarkers. With this background, we aimed to identify metabolites associated with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). METHODS A total of 176 patients with T2DM who have never had a CVD event and 40 who were survivors of coronary artery disease (CAD) events were enrolled. Non-targeted metabolome analysis of fasting plasma samples was performed using gas chromatography coupled with mass spectrometry (GC/MS) highly optimized for multiple measurement of blood samples. First, metabolites were screened by analyzing the association with the established markers of subclinical atherosclerosis (i.e., carotid maximal intima-media thickness (max-IMT) and flow-mediated vasodilation (FMD)) in the non-CVD subjects. Then, the associations between the metabolites detected and the history of CAD were investigated. RESULT A total of 65 annotated metabolites were detected. Non-parametric univariate analysis identified inositol and indoxyl sulfate as significantly (p＜0.05) associated with both max-IMT and FMD. These metabolites were also significantly associated with CAD. Moreover, inositol remained to be associated with CAD even after adjustments for traditional coronary risk factors. CONCLUSIONS We identified novel biomarker candidates for atherosclerosis in Japanese patients with T2DM using GC/MS-based non-targeted metabolomics.
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Affiliation(s)
- Kazuo Omori
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Naoto Katakami
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
- Department of Metabolism and Atherosclerosis, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Shoya Arakawa
- Laboratory of Bioresource Engineering, Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka, Japan
| | - Yuichi Yamamoto
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hiroyo Ninomiya
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Mitsuyoshi Takahara
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
- Department of Diabetes Care Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Taka-aki Matsuoka
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hiroshi Tsugawa
- RIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa, Japan
| | - Masahiro Furuno
- Laboratory of Bioresource Engineering, Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka, Japan
| | - Takeshi Bamba
- Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
| | - Eiichiro Fukusaki
- Laboratory of Bioresource Engineering, Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka, Japan
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
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Saz-Lara A, Álvarez-Bueno C, Martínez-Vizcaíno V, Notario-Pacheco B, Sequí-Dominguez I, Cavero-Redondo I. Are Advanced Glycation End Products in Skin Associated with Vascular Dysfunction Markers? A Meta-Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17186936. [PMID: 32972023 PMCID: PMC7559442 DOI: 10.3390/ijerph17186936] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/29/2020] [Revised: 09/17/2020] [Accepted: 09/20/2020] [Indexed: 12/22/2022]
Abstract
Evidence exists regarding the association between advanced glycation end products and different cardiovascular disease subclinical processes, such as arterial stiffness and atherosclerosis. With this systematic review and meta-analysis, we aimed to provide a synthesis of the evidence regarding the association of arterial stiffness measured by pulse wave velocity and atherosclerosis measured by carotid intima media thickness with skin autofluorescence. A systematic search was performed using: MEDLINE (PubMed), SCOPUS, and Web of Science, until 30 March 2020. Cross-sectional studies or baseline data from prospective longitudinal studies were considered. The DerSimonian and Laird method was used to calculate the pooled estimates of correlation coefficients and the corresponding 95% confidence intervals (CI) for the association of pulse wave velocity and carotid intima media thickness with skin autofluorescence. Twenty-five studies were included in the systematic review and meta-analysis, including 6306 subjects. The pooled correlation coefficient was 0.25 (95% CI: 0.18, 0.31) for pulse wave velocity and skin autofluorescence, and 0.31 (95% CI: 0.25, 0.38) for carotid intima media thickness and skin autofluorescence. This systematic review and meta-analysis provide a synthesis of the evidence showing a positive weak association of pulse wave velocity and carotid intima media thickness with skin autofluorescence.
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Affiliation(s)
- Alicia Saz-Lara
- Health and Social Research Center, Universidad de Castilla-La Mancha, 16171 Cuenca, Spain; (A.S.-L.); (V.M.-V.); (B.N.-P.); (I.S.-D.); (I.C.-R.)
| | - Celia Álvarez-Bueno
- Health and Social Research Center, Universidad de Castilla-La Mancha, 16171 Cuenca, Spain; (A.S.-L.); (V.M.-V.); (B.N.-P.); (I.S.-D.); (I.C.-R.)
- Universidad Politécnica y Artística del Paraguay, 001518 Asuncion, Paraguay
- Correspondence:
| | - Vicente Martínez-Vizcaíno
- Health and Social Research Center, Universidad de Castilla-La Mancha, 16171 Cuenca, Spain; (A.S.-L.); (V.M.-V.); (B.N.-P.); (I.S.-D.); (I.C.-R.)
- Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, 3460000 Talca, Chile
| | - Blanca Notario-Pacheco
- Health and Social Research Center, Universidad de Castilla-La Mancha, 16171 Cuenca, Spain; (A.S.-L.); (V.M.-V.); (B.N.-P.); (I.S.-D.); (I.C.-R.)
| | - Irene Sequí-Dominguez
- Health and Social Research Center, Universidad de Castilla-La Mancha, 16171 Cuenca, Spain; (A.S.-L.); (V.M.-V.); (B.N.-P.); (I.S.-D.); (I.C.-R.)
| | - Iván Cavero-Redondo
- Health and Social Research Center, Universidad de Castilla-La Mancha, 16171 Cuenca, Spain; (A.S.-L.); (V.M.-V.); (B.N.-P.); (I.S.-D.); (I.C.-R.)
- Universidad Politécnica y Artística del Paraguay, 001518 Asuncion, Paraguay
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Tomiyama H, Shiina K. State of the Art Review: Brachial-Ankle PWV. J Atheroscler Thromb 2020; 27:621-636. [PMID: 32448827 PMCID: PMC7406407 DOI: 10.5551/jat.rv17041] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 04/22/2020] [Indexed: 12/11/2022] Open
Abstract
The brachial-ankle pulse wave velocity (brachial-ankle PWV), which is measured simply by wrapping pressure cuffs around the four extremities, is a simple marker to assess the stiffness of the medium- to large- sized arteries. The accuracy and reproducibility of its measurement have been confirmed to be acceptable. Risk factors for cardiovascular disease, especially advanced age and high blood pressure, are reported to be associated with an increase of the arterial stiffness. Furthermore, arterial stiffness might be involved in a vicious cycle with the development/progression of hypertension, diabetes mellitus and chronic kidney disease. Increase in the arterial stiffness is thought to contribute to the development of cardiovascular disease via pathophysiological abnormalities induced in the heart, brain, kidney, and also the arteries themselves. A recent independent participant data meta-analysis conducted in Japan demonstrated that the brachial-ankle PWV is a useful marker to predict future cardiovascular events in Japanese subjects without a previous history of cardiovascular disease, independent of the conventional model for the risk assessment. The cutoff point may be 16.0 m/s in individuals with a low risk of cardiovascular disease (CVD), and 18.0 m/s in individuals with a high risk of CVD and subjects with hypertension. In addition, the method of measurement of the brachial-ankle PWV can also be used to calculate the inter-arm systolic blood pressure difference and ankle-brachial pressure index, which are also useful markers for cardiovascular risk assessment.
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Affiliation(s)
| | - Kazuki Shiina
- Department of Cardiology, Tokyo Medical University, Tokyo, Japan
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21
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Recent Advances and the Potential for Clinical Use of Autofluorescence Detection of Extra-Ophthalmic Tissues. Molecules 2020; 25:molecules25092095. [PMID: 32365790 PMCID: PMC7248908 DOI: 10.3390/molecules25092095] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 04/26/2020] [Accepted: 04/28/2020] [Indexed: 02/07/2023] Open
Abstract
The autofluorescence (AF) characteristics of endogenous fluorophores allow the label-free assessment and visualization of cells and tissues of the human body. While AF imaging (AFI) is well-established in ophthalmology, its clinical applications are steadily expanding to other disciplines. This review summarizes clinical advances of AF techniques published during the past decade. A systematic search of the MEDLINE database and Cochrane Library databases was performed to identify clinical AF studies in extra-ophthalmic tissues. In total, 1097 articles were identified, of which 113 from internal medicine, surgery, oral medicine, and dermatology were reviewed. While comparable technological standards exist in diabetology and cardiology, in all other disciplines, comparability between studies is limited due to the number of differing AF techniques and non-standardized imaging and data analysis. Clear evidence was found for skin AF as a surrogate for blood glucose homeostasis or cardiovascular risk grading. In thyroid surgery, foremost, less experienced surgeons may benefit from the AF-guided intraoperative separation of parathyroid from thyroid tissue. There is a growing interest in AF techniques in clinical disciplines, and promising advances have been made during the past decade. However, further research and development are mandatory to overcome the existing limitations and to maximize the clinical benefits.
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22
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Endothelial Dysfunction and Advanced Glycation End Products in Patients with Newly Diagnosed Versus Established Diabetes: From the CORDIOPREV Study. Nutrients 2020; 12:nu12010238. [PMID: 31963378 PMCID: PMC7019746 DOI: 10.3390/nu12010238] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 01/07/2020] [Accepted: 01/14/2020] [Indexed: 01/22/2023] Open
Abstract
Endothelial dysfunction and intima-media thickness of common carotid arteries (IMT-CC) are considered subclinical markers of atherosclerotic cardiovascular disease (ASCVD). Advanced glycation end products (AGEs) are increased in type 2 diabetes mellitus (T2DM) patients, compared with non-diabetics, being implicated in micro- and macrovascular complications. Our aim was to compare serum AGEs levels and subclinical atherosclerotic markers between patients with established and newly diagnosed T2DM. Among 540 patients with T2DM and coronary heart disease from the CORDIOPREV study, 350 patients had established T2DM and 190 patients had newly diagnosed T2DM. Serum levels of AGEs (methylglyoxal (MG) and N-carboxymethyl lysine (CML)) and subclinical atherosclerotic markers (brachial flow-mediated vasodilation (FMD) and IMT-CC) were measured. AGEs levels (all p < 0.001) and IMT-CC (p = 0.025) were higher in patients with established vs. newly diagnosed T2DM, whereas FMD did not differ between the two groups. Patients with established T2DM and severe endothelial dysfunction (i.e., FMD < 2%) had higher serum MG levels, IMT-CC, HOMA-IR and fasting insulin levels than those with newly diagnosed T2DM and non-severe endothelial dysfunction (i.e., FMD ≥ 2%) (all p < 0.05). Serum CML levels were greater in patients with established vs. newly diagnosed T2DM, regardless of endothelial dysfunction severity. Serum AGEs levels and IMT-CC were significantly higher in patients with established vs. newly diagnosed T2DM, highlighting the progressively increased risk of ASCVD in the course of T2DM. Establishing therapeutic strategies to reduce AGEs production and delay the onset of cardiovascular complications in newly diagnosed T2DM patients or minimize ASCVD risk in established T2DM patients is needed.
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23
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Sánchez E, Betriu À, Yeramian A, Fernández E, Purroy F, Sánchez-de-la-Torre M, Pamplona R, Miquel E, Kerkeni M, Hernández C, Simó R, Lecube A, Hernández M, Rius F, Polanco D, Barbé F, Torres G, Suárez G, Portero-Otin M, Jové M, Colàs-Campàs L, Benabdelhak I, Farràs C, Ortega M, Manuel Valdivielso J, Bermúdez-López M, Martínez-Alonso M. Skin Autofluorescence Measurement in Subclinical Atheromatous Disease: Results from the ILERVAS Project. J Atheroscler Thromb 2019; 26:879-889. [PMID: 30842389 PMCID: PMC6800392 DOI: 10.5551/jat.47498] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Aim: Advanced glycation end-products (AGEs) have been involved in the atherogenic process in the high-risk population. The goal of this study was to demonstrate that AGEs are related to subclinical atheromatous disease in subjects with low to moderate vascular risk. Methods: A cross-sectional study in which 2,568 non-diabetic subjects of both sexes without cardiovascular disease were included. Subcutaneous content of AGEs was assessed by skin autofluorescence (SAF) and subclinical atheromatous disease was measured by assessing the atheromatous plaque burden in carotid and femoral regions using ultrasonography. In addition, serum pentosidine, carboxymethyl-lysine (CML) and AGE receptors (RAGE) were assessed in a nested case-control study with 41 subjects without plaque and 41 individuals subjects with generalized disease. Results: Patients with atheromatous plaque had a higher SAF than those with no plaque (1.9 [1.7 to 2.3] vs. 1.8 [1.6 to 2.1] arbitrary units (AU), p % 0.001). The SAF correlated with the total number of affected regions (r = 0.171, p < 0.001), increasing progressively from 1.8 [1.6 to 2.1] AU in those without atheromatous disease to 2.3 [1.9 to 2.7] AU in patients with ≥ 8 plaques (p < 0.001). A correlation was also observed between SAF and the total plaque area (r = 0.113, p < 0.001). The area under the Receiver Operating Characteristic curve was 0.65 (0.61 to 0.68) for identifying male subjects with atheromatous disease. The multivariable logistic regression model showed a significant and independent association between SAF and the presence of atheromatous disease. However, no significant differences in serum pentosidine, CML, and RAGE were observed. Conclusions: Increased subcutaneous content of AGEs is associated with augmented atheromatous plaque burden. Our results suggest that SAF may provide clinically relevant information to the current strategies for the evaluation of cardiovascular risk, especially among the male population.
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Affiliation(s)
- Enric Sánchez
- Endocrinology and Nutrition Department. University Hospital Arnau de Vilanova. Obesity, Diabetes and Metabolism (ODIM) research group. IRBLleida. University of Lleida
| | - Àngels Betriu
- Unit for the Detection and Treatment of Atherothrombotic Diseases (UDETMA V&R). University Hospital Arnau de Vilanova. Vascular and Renal Translational Research Group. IRBLleida. University of Lleida
| | - Andree Yeramian
- Endocrinology and Nutrition Department. University Hospital Arnau de Vilanova. Obesity, Diabetes and Metabolism (ODIM) research group. IRBLleida. University of Lleida
| | - Elvira Fernández
- Unit for the Detection and Treatment of Atherothrombotic Diseases (UDETMA V&R). University Hospital Arnau de Vilanova. Vascular and Renal Translational Research Group. IRBLleida. University of Lleida
| | - Francesc Purroy
- Stroke Unit. University Hospital Arnau de Vilanova. Clinical Neurosciences Group. IRBLleida. University of Lleida
| | - Manuel Sánchez-de-la-Torre
- Respiratory Department. University Hospital Arnau de Vilanova-Santa Maria. Translational Research in Respiratory Medicine. IRBLleida. University of Lleida.,Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII)
| | - Reinald Pamplona
- Department of Experimental Medicine. IRBLleida. University of Lleida
| | - Eva Miquel
- Borges Blanques Primary Health Care Unit
| | - Mohsen Kerkeni
- Laboratory of Biochemistry, LR12ES05, Faculty of Medicine, University of Monastir
| | - Cristina Hernández
- Endocrinology and Nutrition Department, University Hospital Vall d'Hebron. Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR). Universitat Autònoma de Barcelona.,Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII)
| | - Rafael Simó
- Endocrinology and Nutrition Department, University Hospital Vall d'Hebron. Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR). Universitat Autònoma de Barcelona.,Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII)
| | - Albert Lecube
- Endocrinology and Nutrition Department. University Hospital Arnau de Vilanova. Obesity, Diabetes and Metabolism (ODIM) research group. IRBLleida. University of Lleida.,Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII)
| | | | | | - Marta Hernández
- Endocrinology and Nutrition Department. University Hospital Arnau de Vilanova. Obesity, Diabetes and Metabolism (ODIM) research group. IRBLleida. University of Lleida
| | - Ferran Rius
- Endocrinology and Nutrition Department. University Hospital Arnau de Vilanova. Obesity, Diabetes and Metabolism (ODIM) research group. IRBLleida. University of Lleida
| | - Dinora Polanco
- Respiratory Department. University Hospital Arnau de Vilanova-Santa Maria. Translational Research in Respiratory Medicine. IRBLleida. University of Lleida
| | - Ferran Barbé
- Respiratory Department. University Hospital Arnau de Vilanova-Santa Maria. Translational Research in Respiratory Medicine. IRBLleida. University of Lleida.,Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII)
| | - Gerard Torres
- Respiratory Department. University Hospital Arnau de Vilanova-Santa Maria. Translational Research in Respiratory Medicine. IRBLleida. University of Lleida.,Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII)
| | - Guillermo Suárez
- Respiratory Department. University Hospital Arnau de Vilanova-Santa Maria. Translational Research in Respiratory Medicine. IRBLleida. University of Lleida.,Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII)
| | | | - Mariona Jové
- Department of Experimental Medicine. IRBLleida. University of Lleida
| | - Laura Colàs-Campàs
- Stroke Unit. University Hospital Arnau de Vilanova. Clinical Neurosciences Group. IRBLleida. University of Lleida
| | - Ikram Benabdelhak
- Stroke Unit. University Hospital Arnau de Vilanova. Clinical Neurosciences Group. IRBLleida. University of Lleida
| | | | | | - José Manuel Valdivielso
- Unit for the Detection and Treatment of Atherothrombotic Diseases (UDETMA V&R). University Hospital Arnau de Vilanova. Vascular and Renal Translational Research Group. IRBLleida. University of Lleida
| | - Marcelino Bermúdez-López
- Unit for the Detection and Treatment of Atherothrombotic Diseases (UDETMA V&R). University Hospital Arnau de Vilanova. Vascular and Renal Translational Research Group. IRBLleida. University of Lleida
| | - Montse Martínez-Alonso
- Unit for the Detection and Treatment of Atherothrombotic Diseases (UDETMA V&R). University Hospital Arnau de Vilanova. Vascular and Renal Translational Research Group. IRBLleida. University of Lleida
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24
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Hitsumoto T. Clinical Impact of Blood Testosterone Concentration on Cardio-Ankle Vascular Index in Female Patients With Type 2 Diabetes Mellitus. Cardiol Res 2019; 10:9-17. [PMID: 30834054 PMCID: PMC6396806 DOI: 10.14740/cr827] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2018] [Accepted: 01/07/2019] [Indexed: 12/17/2022] Open
Abstract
Background Information regarding testosterone as a significant risk factor of cardiovascular disease (CVD) in female patients with type 2 diabetes mellitus (DM) is limited. However, some clinical studies reported the importance of cardio-ankle vascular index (CAVI) as a novel physiological marker of arterial function in type 2 DM. This cross-sectional study aimed to elucidate the clinical effects of blood testosterone concentration on CAVI in female patients with type 2 DM. Methods A total of 238 postmenopausal patients including 97 with a history of CVD with type 2 DM (age (mean ± standard deviation (SD)), 73 ± 9 years) were enrolled. CAVI was measured according to the standard technique, and serum total testosterone concentration (T-T) was also measured as a testosterone level marker in vivo. The relationship between CAVI and T-T was evaluated. Results CAVI is significantly higher (CVD vs. non-CVD: 10.2 ± 1.2 vs. 9.2 ± 1.0, P < 0.001), and log-T-T significantly lower (CVD vs. non-CVD: 1.2 ± 0.2 ng/dL vs. 1.5 ± 0.2 ng/dL, P < 0.001) in patients with CVD than those without CVD. CAVI was significantly negatively correlated with log-T-T (r = -0.41; P < 0.001). Furthermore, multiple regression analysis indicated that CVD (β = 0.23; P < 0.001) and log-T-T (β = -0.18; P < 0.01) were selected as independent subordinate variables for CAVI. Conclusions This study showed that T-T was independently inversely associated with CAVI, indicating that low testosterone concentration is a considerable risk factor for the progression of arterial dysfunction in female patients with type 2 DM.
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Affiliation(s)
- Takashi Hitsumoto
- Hitsumoto Medical Clinic, 2-7-7, Takezakicyou, Shimonoseki City, Yamaguchi, 750-0025, Japan.
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