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Qiu Z, Jia X, Li Y, Fu Y, Xiao Y. Screen time in the development of type 2 diabetes mellitus (T2DM) : a two-sample Mendelian randomization study. Endocrine 2024; 85:158-167. [PMID: 38347339 DOI: 10.1007/s12020-024-03723-5] [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: 11/08/2023] [Accepted: 01/30/2024] [Indexed: 07/14/2024]
Abstract
OBJECTIVE This study aimed to investigate the potential causal relationship between screen time and the risk of developing type 2 diabetes mellitus (T2DM) using Mendelian randomization. METHODS Two-sample Mendelian randomization was conducted, utilizing genetic variants associated with different types of screen time as instrumental variables. Single nucleotide polymorphisms (SNPs) were used to assess the primary outcome, which was the risk of developing T2DM. RESULTS The analysis revealed a significant positive causal association between television viewing time and the risk of T2DM. Specifically, excessive television viewing time was found to increase the risk of developing T2DM (OR: 2.39, 95% CI: 1.90 to 3.00, P < 0.01). However, no significant causal relationship was observed between computer usage time and the risk of T2DM. Additionally, mobile phone use time showed a positive correlation with the risk of T2DM (OR: 1.31, 95% CI: 1.04 to 1.64, P = 0.02), albeit to a lesser extent than television viewing time. CONCLUSION The findings of this study indicate a significant causal association between certain types of screen time, specifically television viewing and mobile phone use, and an increased risk of T2DM.
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Affiliation(s)
- Zhengqi Qiu
- Faculty of Medicine, Macau University of Science and Technology, Est. Seak Pai Van Praia Park, Rés-Do-Chão R, Coloane, Macao, 999078, China
| | - Xueyuan Jia
- Faculty of Medicine, Macau University of Science and Technology, Est. Seak Pai Van Praia Park, Rés-Do-Chão R, Coloane, Macao, 999078, China
| | - Yufei Li
- Faculty of Medicine, Macau University of Science and Technology, Est. Seak Pai Van Praia Park, Rés-Do-Chão R, Coloane, Macao, 999078, China
| | - Yancheng Fu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518060, China
| | - Ying Xiao
- Faculty of Medicine, Macau University of Science and Technology, Est. Seak Pai Van Praia Park, Rés-Do-Chão R, Coloane, Macao, 999078, China.
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Bayoumi R, Farooqi M, Alawadi F, Hassanein M, Osama A, Mukhopadhyay D, Abdul F, Sulaiman F, Dsouza S, Mulla F, Ahmed F, AlSharhan M, Khamis A. Etiologies underlying subtypes of long-standing type 2 diabetes. PLoS One 2024; 19:e0304036. [PMID: 38805513 PMCID: PMC11132508 DOI: 10.1371/journal.pone.0304036] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 05/05/2024] [Indexed: 05/30/2024] Open
Abstract
BACKGROUND Attempts to subtype, type 2 diabetes (T2D) have mostly focused on newly diagnosed European patients. In this study, our aim was to subtype T2D in a non-white Emirati ethnic population with long-standing disease, using unsupervised soft clustering, based on etiological determinants. METHODS The Auto Cluster model in the IBM SPSS Modeler was used to cluster data from 348 Emirati patients with long-standing T2D. Five predictor variables (fasting blood glucose (FBG), fasting serum insulin (FSI), body mass index (BMI), hemoglobin A1c (HbA1c) and age at diagnosis) were used to determine the appropriate number of clusters and their clinical characteristics. Multinomial logistic regression was used to validate clustering results. RESULTS Five clusters were identified; the first four matched Ahlqvist et al subgroups: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), and a fifth new subtype of mild early onset diabetes (MEOD). The Modeler algorithm allows for soft assignments, in which a data point can be assigned to multiple clusters with different probabilities. There were 151 patients (43%) with membership in cluster peaks with no overlap. The remaining 197 patients (57%) showed extensive overlap between clusters at the base of distributions. CONCLUSIONS Despite the complex picture of long-standing T2D with comorbidities and complications, our study demonstrates the feasibility of identifying subtypes and their underlying causes. While clustering provides valuable insights into the architecture of T2D subtypes, its application to individual patient management would remain limited due to overlapping characteristics. Therefore, integrating simplified, personalized metabolic profiles with clustering holds greater promise for guiding clinical decisions than subtyping alone.
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Affiliation(s)
- Riad Bayoumi
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | | | - Fatheya Alawadi
- Endocrinology Department, Dubai Hospital, Dubai Health, Dubai, UAE
| | | | - Aya Osama
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | - Debasmita Mukhopadhyay
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | - Fatima Abdul
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | - Fatima Sulaiman
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | - Stafny Dsouza
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | - Fahad Mulla
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | - Fayha Ahmed
- Pathology Department, Dubai Hospital, Dubai Health, Dubai, UAE
| | - Mouza AlSharhan
- Pathology Department, Dubai Hospital, Dubai Health, Dubai, UAE
| | - Amar Khamis
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
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Tranter JD, Kumar A, Nair VK, Sah R. Mechanosensing in Metabolism. Compr Physiol 2023; 14:5269-5290. [PMID: 38158369 PMCID: PMC11681368 DOI: 10.1002/cphy.c230005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2024]
Abstract
Electrical mechanosensing is a process mediated by specialized ion channels, gated directly or indirectly by mechanical forces, which allows cells to detect and subsequently respond to mechanical stimuli. The activation of mechanosensitive (MS) ion channels, intrinsically gated by mechanical forces, or mechanoresponsive (MR) ion channels, indirectly gated by mechanical forces, results in electrical signaling across lipid bilayers, such as the plasma membrane. While the functions of mechanically gated channels within a sensory context (e.g., proprioception and touch) are well described, there is emerging data demonstrating functions beyond touch and proprioception, including mechanoregulation of intracellular signaling and cellular/systemic metabolism. Both MR and MS ion channel signaling have been shown to contribute to the regulation of metabolic dysfunction, including obesity, insulin resistance, impaired insulin secretion, and inflammation. This review summarizes our current understanding of the contributions of several MS/MR ion channels in cell types implicated in metabolic dysfunction, namely, adipocytes, pancreatic β-cells, hepatocytes, and skeletal muscle cells, and discusses MS/MR ion channels as possible therapeutic targets. © 2024 American Physiological Society. Compr Physiol 14:5269-5290, 2024.
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Affiliation(s)
- John D. Tranter
- Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Ashutosh Kumar
- Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Vinayak K. Nair
- Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Rajan Sah
- Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA
- Center for Cardiovascular Research, Washington University, St. Louis, Missouri, USA
- St. Louis VA Medical Center, St. Louis, Missouri, USA
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Saruarov Y, Nuskabayeva G, Gencer MZ, Sadykova K, Zhunissova M, Tatykayeva U, Iskandirova E, Sarsenova G, Durmanova A, Gaipov A, Atageldiyeva K, Sarría-Santamera A. Associations of Clusters of Cardiovascular Risk Factors with Insulin Resistance and Β-Cell Functioning in a Working-Age Diabetic-Free Population in Kazakhstan. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:3918. [PMID: 36900929 PMCID: PMC10001384 DOI: 10.3390/ijerph20053918] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 02/14/2023] [Accepted: 02/20/2023] [Indexed: 06/18/2023]
Abstract
Cardiovascular risk factors aggregate in determined individuals. Patients with Type 2 diabetes mellitus (T2DM) have higher cardiovascular This study aimed to investigate insulinresistance (IR) and β-cell function using the homeostasis model assessment (HOMA) indexes in a general Kazakh population and determine the effect he effect that cardiovascular factors may have on those indexes. We conducted a cross-sectional study among employees of the Khoja Akhmet Yassawi International Kazakh-Turkish University (Turkistan, Kazakhstan) aged between 27 and 69 years. Sociodemographic variables, anthropometric measurements (body mass, height, waist circumference, hip circumference), and blood pressure were obtained. Fasting blood samples were collected to measure insulin, glucose, total cholesterol (TC), triglycerides (TG), and high- (HDL) andlow-density lipoprotein (LDL) levels. Oral glucose tolerance tests were performed. Hierarchical and K-means cluster analyses were obtained. The final sample was composed of 427 participants. Spearmen correlation analysis showed that cardiovascular parameters were statistically associated with HOMA-β (p < 0.001) and not with HOMA IR. Participants were aggregated into the three clusters where the cluster with a higher age and cardiovascular risk revealed deficient β-cell functioning, but not IR (p < 0.000 and p = 0.982). Common and easy to obtain biochemical and anthropometric measurements capturing relevant cardiovascular risk factors have been demonstrated to be associated with significant deficiency in insulin secretion. Although further longitudinal studies of the incidence of T2DM are needed, this study highlights that cardiovascular profiling has a significant role not just for risk stratification of patients for cardiovascular prevention but also for targeted vigilant glucose monitoring.
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Affiliation(s)
- Yerbolat Saruarov
- Department of Special Clinical Disciplines, Faculty of Medicine, Khoja Akhmet Yassawi International Kazakh-Turkish University, Turkistan 161200, Kazakhstan
| | - Gulnaz Nuskabayeva
- Department of Special Clinical Disciplines, Faculty of Medicine, Khoja Akhmet Yassawi International Kazakh-Turkish University, Turkistan 161200, Kazakhstan
| | - Mehmet Ziya Gencer
- Department of Special Clinical Disciplines, Faculty of Medicine, Khoja Akhmet Yassawi International Kazakh-Turkish University, Turkistan 161200, Kazakhstan
| | - Karlygash Sadykova
- Department of Special Clinical Disciplines, Faculty of Medicine, Khoja Akhmet Yassawi International Kazakh-Turkish University, Turkistan 161200, Kazakhstan
| | - Mira Zhunissova
- Department of Special Clinical Disciplines, Faculty of Medicine, Khoja Akhmet Yassawi International Kazakh-Turkish University, Turkistan 161200, Kazakhstan
| | - Ugilzhan Tatykayeva
- Department of Human Pathology and Physiology, Faculty of Dentistry, Khoja Akhmet Yassawi International Kazakh-Turkish University, Turkistan 161200, Kazakhstan
| | - Elmira Iskandirova
- Department of Therapy, Shymkent Medical Institute, Khoja Akhmet Yassawi International Kazakh-Turkish University, Shymkent 160019, Kazakhstan
| | - Gulmira Sarsenova
- Department of Therapy, Shymkent Medical Institute, Khoja Akhmet Yassawi International Kazakh-Turkish University, Shymkent 160019, Kazakhstan
| | - Aigul Durmanova
- Academic Department of Internal Medicine, University Medical Center, Astana 020000, Kazakhstan
| | - Abduzhappar Gaipov
- Academic Department of Internal Medicine, University Medical Center, Astana 020000, Kazakhstan
- Department of Medicine, Nazarbayev University School of Medicine, Astana 020000, Kazakhstan
| | - Kuralay Atageldiyeva
- Academic Department of Internal Medicine, University Medical Center, Astana 020000, Kazakhstan
- Department of Medicine, Nazarbayev University School of Medicine, Astana 020000, Kazakhstan
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Kohlenberg JD, Laurenti MC, Egan AM, Wismayer DS, Bailey KR, Cobelli C, Man CD, Vella A. Differential contribution of alpha and beta cell dysfunction to impaired fasting glucose and impaired glucose tolerance. Diabetologia 2023; 66:201-212. [PMID: 36112169 PMCID: PMC9742343 DOI: 10.1007/s00125-022-05794-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 08/02/2022] [Indexed: 12/14/2022]
Abstract
AIMS/HYPOTHESIS People with isolated impaired fasting glucose (IFG) have normal beta cell function. We hypothesised that an increased glucose threshold for beta cell secretion explains IFG. METHODS We used graded glucose infusion to examine the relationship of insulin secretion rate (ISR) and glucagon secretion rate (GSR) with rising glucose. We studied 39 non-diabetic individuals (53 ± 2 years, BMI 30 ± 1 kg/m2), categorised by fasting glucose and glucose tolerance status. After an overnight fast, a variable insulin infusion was used to maintain glucose at ~4.44 mmol/l (07:00 to 08:30 hours). At 09:00 hours, graded glucose infusion commenced at 1 mg kg-1 min-1 and doubled every 60 min until 13:00 hours. GSR and ISR were calculated by nonparametric deconvolution from concentrations of glucagon and C-peptide, respectively. RESULTS The relationship of ISR with glucose was linear and the threshold for insulin secretion in isolated IFG did not differ from that in people with normal fasting glucose and normal glucose tolerance. GSR exhibited a single-exponential relationship with glucose that could be characterised by G50, the change in glucose necessary to suppress GSR by 50%. G50 was increased in IFG compared with normal fasting glucose regardless of the presence of impaired or normal glucose tolerance. CONCLUSIONS/INTERPRETATION These data show that, in non-diabetic humans, alpha cell dysfunction contributes to the pathogenesis of IFG independently of defects in insulin secretion. We also describe a new index that quantifies the suppression of glucagon secretion by glucose.
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Affiliation(s)
- Jacob D Kohlenberg
- Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Marcello C Laurenti
- Biomedical Engineering and Physiology Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN, USA
| | - Aoife M Egan
- Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Daniel Schembri Wismayer
- Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Kent R Bailey
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | - Claudio Cobelli
- Department of Women's and Children's Health, University of Padova, Padova, Italy
| | - Chiara Dalla Man
- Department of Information Engineering, University of Padova, Padova, Italy
| | - Adrian Vella
- Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic College of Medicine, Rochester, MN, USA.
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Mamedov MN, Mardanov BU, Kokozheva MA, Shukurov FB, Akhundova HR, Kutsenko VA. Analysis of myocardial revascularization and endpoints after a 1-year follow-up of patients with acute and chronic coronary artery disease, depending on diabetes presence. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2022; 21:3394. [DOI: 10.15829/1728-8800-2022-3394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Aim. To analyze myocardial revascularization in patients with acute and chronic coronary artery disease (CAD) and with different glycemic status, as well as to evaluate complications after a 1-year follow-up.Material and methods. This prospective comparative clinical study included 202 patients of both sexes with acute and chronic coronary artery disease. Depending on the glycemic status and CAD type, the patients were divided into four groups: acute CAD and type 2 diabetes (T2D); acute CAD without T2D (control group); chronic CAD and T2D; chronic CAD without DM2 (control group). Depending on the clinical condition and the results of coronary angiography, patients underwent various types of myocardial revascularization: balloon angioplasty without stenting, stenting, coronary artery bypass grafting, stenting + coronary artery bypass grafting. One year after discharge, all patients were contacted to evaluate complications and endpoints, which included recurrent myocardial infarction, cerebrovascular accident, readmission, revascularization, and death. Total indicator of endpoints was assessed.Results. Up to 80% of patients with acute and chronic CAD, regardless of glycemic status, underwent revascularization, mainly stenting. The prevalence of stenting among persons without T2D with acute and chronic CAD was significantly higher compared with patients with T2D. The absolute number of patients with coronary artery bypass grafting, including in combination with stenting, was higher in the T2D groups. In groups without T2D, the number of patients with one stent was 2-2,5 times higher compared to groups with T2D — acute CAD (p=0,041) and chronic CAD (p=0,017). The prevalence of implantation of ≥2 stents did not differ between the groups. Within 1 year after discharge, there were more hospitalizations and reoperations among people with acute and chronic CAD and T2D. The groups did not differ in the number of non-fatal and fatal complications, although the absolute numbers of these indicators were higher in patients with T2D. The total number of endpoints in T2D people, regardless of the CAD type, were 2 times higher compared to the corresponding control groups (p<0,001).Conclusion. Most patients with acute and chronic CAD, regardless of glycemic status, underwent myocardial revascularization. In patients without T2D, stenting prevailed, most often of one coronary artery. Patients with T2D, along with stenting, underwent coronary bypass grafting, as well as a combination of these two procedures. After a year of follow-up, the number of complications in patients with T2D was 2 times higher compared to patients without type 2 diabetes, which emphasizes the importance of secondary prevention, including complex drug treatment.
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Affiliation(s)
- M. N. Mamedov
- National Medical Research Center for Therapy and Preventive Medicine
| | - B. U. Mardanov
- National Medical Research Center for Therapy and Preventive Medicine
| | - M. A. Kokozheva
- National Medical Research Center for Therapy and Preventive Medicine
| | - F. B. Shukurov
- National Medical Research Center for Therapy and Preventive Medicine
| | - H. R. Akhundova
- National Medical Research Center for Therapy and Preventive Medicine
| | - V. A. Kutsenko
- National Medical Research Center for Therapy and Preventive Medicine
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Stidsen JV, Christensen DH, Henriksen JE, Højlund K, Olsen MH, Thomsen RW, Christensen LB, Nielsen JS, Olesen TB, Beck-Nielsen H. Risk of cardiovascular events associated with pathophysiological phenotypes of type 2 diabetes. Eur J Endocrinol 2022; 187:279-291. [PMID: 35670619 DOI: 10.1530/eje-22-0020] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 06/06/2022] [Indexed: 11/08/2022]
Abstract
OBJECTIVE Hyperglycaemia in type 2 diabetes is caused by varying degrees of two defects: low insulin sensitivity and beta-cell dysfunction. We assessed if subgrouping of patients into three pathophysiological phenotypes according to these defects could identify individuals with high or low risk of future cardiovascular events. DESIGN This is a prospective cohort study. METHODS We assessed estimates of insulin sensitivity and beta-cell function from the homeostasis model assessment-2 in 4209 individuals with recently diagnosed type 2 diabetes enrolled from general practitioners and outpatient clinics in Denmark. Individuals were followed for a composite cardiovascular endpoint (either atherosclerotic outcomes (myocardial infarction, unstable angina pectoris, stroke, coronary or peripheral revascularization), heart failure, or cardiovascular death) and all-cause mortality. RESULTS Totally 417 individuals with the insulinopenic phenotype (high insulin sensitivity and low beta-cell function) had substantially lower risk of cardiovascular events (5-year cumulative incidence: 4.6% vs 10.1%; age-/sex-adjusted hazard ratio (aHR): 0.49; 95% CI: 0.30-0.82) compared with 2685 individuals with the classical phenotype (low insulin sensitivity and low beta-cell function), driven by atherosclerotic events. Conversely, 1107 individuals with the hyperinsulinaemic phenotype (low insulin sensitivity and high beta-cell function) had more cardiovascular events (5-year cumulative incidence: 12.6%; aHR: 1.33; 95% CI: 1.05-1.69), primarily driven by increased heart failure and cardiovascular death and increased all-cause mortality. CONCLUSIONS Simple phenotyping based on insulin sensitivity and beta-cell function predicts distinct future risks of cardiovascular events and death in patients with type 2 diabetes. These results suggest that precision medicine according to underlying type 2 pathophysiology potentially can reduce diabetes complications.
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Affiliation(s)
| | | | - Jan Erik Henriksen
- Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark
| | - Kurt Højlund
- Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense C, Denmark
| | - Michael Hecht Olsen
- Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
- Cardiology Section, Department of Internal Medicine and Steno Diabetes Center Zealand, Holbæk Hospital, Holbæk, Denmark
| | | | | | - Jens Steen Nielsen
- Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense C, Denmark
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Lai HT, Imamura F, Korat AVA, Murphy RA, Tintle N, Bassett JK, Chen J, Kröger J, Chien KL, Senn M, Wood AC, Forouhi NG, Schulze MB, Harris WS, Vasan RS, Hu F, Giles GG, Hodge A, Djousse L, Brouwer IA, Qian F, Sun Q, Wu JH, Marklund M, Lemaitre RN, Siscovick DS, Fretts AM, Shadyab AH, Manson JE, Howard BV, Robinson JG, Wallace RB, Wareham NJ, Chen YDI, Rotter JI, Tsai MY, Micha R, Mozaffarian D, the Fatty Acids and Outcomes Research Consortium (FORCE). Trans Fatty Acid Biomarkers and Incident Type 2 Diabetes: Pooled Analysis of 12 Prospective Cohort Studies in the Fatty Acids and Outcomes Research Consortium (FORCE). Diabetes Care 2022; 45:854-863. [PMID: 35142845 PMCID: PMC9114723 DOI: 10.2337/dc21-1756] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 01/10/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis. RESEARCH DESIGN AND METHODS We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged ≥18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics. RESULTS During a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94-1.25); cis/trans-18:2, 0.89 (0.73-1.07); and trans/cis-18:2, 0.87 (0.73-1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67-0.99], 0.86 [0.75-0.99], and 0.84 [0.74-0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P ≥ 0.1). CONCLUSIONS Circulating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels.
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Affiliation(s)
- Heidi T.M. Lai
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA
- Department of Primary Care and Public Health, Imperial College London, London, U.K
| | - Fumiaki Imamura
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K
| | - Andres V. Ardisson Korat
- Department of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Rachel A. Murphy
- School of Population & Public Health, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Nathan Tintle
- Department of Mathematics and Statistics, Dordt University, Sioux Center, IA
- Fatty Acid Research Institute, Sioux Falls, SD
| | - Julie K. Bassett
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
| | - Jiaying Chen
- Division of Aging, Brigham and Women's Hospital, Boston, MA
| | - Janine Kröger
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Kuo-Liong Chien
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Republic of China
| | - Mackenzie Senn
- U.S. Department of Agriculture/Agriculture Research Service Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX
| | - Alexis C. Wood
- U.S. Department of Agriculture/Agriculture Research Service Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX
| | - Nita G. Forouhi
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K
| | - Matthias B. Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
| | - William S. Harris
- Fatty Acid Research Institute, Sioux Falls, SD
- Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD
| | - Ramachandran S. Vasan
- Boston University School of Medicine, Boston, MA
- The Framingham Heart Study, Framingham, MA
| | - Frank Hu
- Department of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Graham G. Giles
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
- Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Allison Hodge
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
| | - Luc Djousse
- Divisions of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Ingeborg A. Brouwer
- Department of Health Sciences, Faculty of Science, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
| | - Frank Qian
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Qi Sun
- Department of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Jason H.Y. Wu
- The George Institute for Global Health, the Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Matti Marklund
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA
- The George Institute for Global Health, the Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
- Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden
| | - Rozenn N. Lemaitre
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA
| | | | - Amanda M. Fretts
- Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington School of Public Health, Seattle, WA
| | - Aladdin H. Shadyab
- Family Medicine and Public Health, School of Medicine, University of California, San Diego, La Jolla, CA
| | - JoAnn E. Manson
- Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Barbara V. Howard
- Georgetown University Medical Center, Georgetown University, Hyattsville, MD
| | | | | | - Nick J. Wareham
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K
| | - Yii-Der Ida Chen
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA
| | - Jerome I. Rotter
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA
| | - Michael Y. Tsai
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN
| | - Renata Micha
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA
| | - Dariush Mozaffarian
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA
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Li JS, Ji T, Su SL, Zhu Y, Chen XL, Shang EX, Guo S, Qian DW, Duan JA. Mulberry leaves ameliorate diabetes via regulating metabolic profiling and AGEs/RAGE and p38 MAPK/NF-κB pathway. JOURNAL OF ETHNOPHARMACOLOGY 2022; 283:114713. [PMID: 34626776 DOI: 10.1016/j.jep.2021.114713] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 10/01/2021] [Accepted: 10/04/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Mulberry leaves have been used as traditional hypoglycemic medicine-food plant for thousand years in China. According to traditional Chinese medicine theory, type 2 diabetes mellitus (T2DM) belongs to the category of XiaoKe. Presently, the research of mulberry leaf hypoglycemic and lipid-lowering direction is mature, but the curative effects of alkaloids, flavonoids, polysaccharides, and other bioactive ingredients and the related mechanism is still unclear. AIM OF THE STUDY This paper aims to study the efficacy and mechanism of alkaloids, flavonoids, polysaccharides, and other bioactive components in mulberry leaves in the treatment of T2DM individually. MATERIALS AND METHODS The determination of levels of fasting blood glucose (FBG), triglyceride (TG) and total cholesterol (T-Cho), and pyruvate kinase (PK), hexokinase (HK), and alanine aminotransferase (ALT/GPT) of in plasma of diabetic mice. Urine metabolomics was analyzed by UPLC-QTOF/MS to evaluate differential metabolites from multiple metabolic pathways. The glucose uptake of HepG2 cells and 3T3-L1 cells. Expression of Caspase-3 and caspase-9, inflammatory injury and p38MAPK/NF-κB signaling pathway in GLUTag cells. RESULTS Our study revealed alkaloids, flavonoids, and polysaccharides in mulberry leaf could increase the levels of PK, HK, and ALT/GPT, and decrease the levels of TG and T-Cho significantly, and regulate glucose, amino acid, and lipid metabolism. Furthermore, 1-deoxynojirimycin (DNJ) and isoquercitrin (QG) both could increase glucose uptake and promote differentiation of HepG2 cells, increase PPARγ, C/EBPα and SREBP-l expression in 3T3-L1 cells, and inhibit AGEs-induced injury and apoptosis in GLUTag cells, reduce the expression of proteins related to AGEs/RAGE and p38MAPK/NF-κB pathway. Notably, isoquercitrin exhibited more pronounced anti-diabetic efficacy. CONCLUSIONS The alkaloids, flavonoids, and polysaccharides from mulberry leaf exhibited hypoglycemic activity through the regulation of glucose, amino acid, and lipid metabolism. 1-DNJ and QG increased glucose uptake and promoted differentiation of HepG2 cells, increased PPARγ, C/EBPα and SREBP-l expression in 3T3-L1 cells, and inhibited AGEs-induced injury and apoptosis in GLUTag cells via the AGEs/RAGE and p38 MAPK/NF-κB pathway.
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Affiliation(s)
- Jia-Shang Li
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, And Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Tao Ji
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, And Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Shu-Lan Su
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, And Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Yue Zhu
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, And Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Xing-Ling Chen
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, And Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Er-Xin Shang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, And Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Sheng Guo
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, And Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Da-Wei Qian
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, And Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Jin-Ao Duan
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, And Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
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Lemaitre RN, Jensen PN, Wang Z, Fretts AM, McKnight B, Nemet I, Biggs ML, Sotoodehnia N, de Oliveira Otto MC, Psaty BM, Siscovick DS, Hazen SL, Mozaffarian D. Association of Trimethylamine N-Oxide and Related Metabolites in Plasma and Incident Type 2 Diabetes: The Cardiovascular Health Study. JAMA Netw Open 2021; 4:e2122844. [PMID: 34448864 PMCID: PMC8397925 DOI: 10.1001/jamanetworkopen.2021.22844] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
IMPORTANCE Although rodent studies suggest that trimethylamine N-oxide (TMAO) influences glucose homeostasis and risk of type 2 diabetes, evidence in humans is limited. OBJECTIVE To examine the associations of serial measures of plasma TMAO and related metabolite concentrations with incident type 2 diabetes, fasting plasma insulin and glucose levels, and the Gutt insulin sensitivity index (ISI). DESIGN, SETTING, AND PARTICIPANTS This prospective cohort design assessed the association of plasma TMAO and related metabolite concentrations with diabetes outcome, whereas a cross-sectional design assessed the association with insulin and glucose levels and Gutt ISI. The participants were a cohort of older US adults from the Cardiovascular Health Study (CHS). Data from June 1989 to May 1990, from November 1992 to June 1993, and from June 1995 to June 1997 were included, with follow-up through June 2010. Levels of TMAO and related metabolites were measured in CHS plasma samples. Data were analyzed from July 2019 to September 2020. EXPOSURES Plasma concentrations of TMAO, carnitine, betaine, choline, crotonobetaine, and γ-butyrobetaine, measured by high-performance liquid chromatography and mass spectrometry. MAIN OUTCOMES AND MEASURES Linear regression for associations of TMAO and related metabolites with insulin and glucose levels and Gutt ISI, and proportional hazards regression for associations with diabetes. RESULTS The study included 4442 participants without diabetes at baseline (mean [SD] age, 73 [6] years at entry; 2710 [61%] women). In multivariable analyses, plasma TMAO, carnitine, crotonobetaine, and γ-butyrobetaine concentrations were positively associated with fasting insulin level (insulin mean geometric ratio comparing fifth with first quintiles of metabolite concentration: 1.07 [95% CI, 1.04-1.10] for TMAO; 1.07 [95% CI, 1.03-1.10] for carnitine; 1.05 [95% CI, 1.02-1.08] for crotonobetaine; and 1.06 [95% CI, 1.02-1.09] for γ-butyrobetaine). In contrast, betaine and choline concentrations were associated with greater insulin sensitivity (mean difference in Gutt ISI comparing fifth with first quintiles: 6.46 [95% CI, 4.32-8.60] and 2.27 [95% CI, 0.16-4.38], respectively). Incident diabetes was identified in 661 participants during a median 12.1 (interquartile range, 6.9-17.1) years of follow-up. In multivariable analyses, TMAO and metabolites were not significantly associated with type 2 diabetes risk (hazard ratios of diabetes comparing fifth with first quintile: 1.20 [95% CI, 0.94-1.55] for TMAO; 0.96 [95% CI, 0.74-1.24] for choline; 0.88 [95% CI, 0.67-1.15] for betaine; 1.07 [95% CI, 0.83-1.37] for carnitine; 0.79 [95% CI, 0.60-1.04] for γ-butyrobetaine; and 1.06 [95% CI, 0.83-1.35] for crotonobetaine). CONCLUSIONS AND RELEVANCE Plasma TMAO and related metabolites were not significantly associated with type 2 diabetes among older adults. The metabolites TMAO, carnitine, γ-butyrobetaine, and crotonobetaine may be associated with insulin resistance, and betaine and choline may be associated with greater insulin sensitivity, but temporality of the associations was not established.
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Affiliation(s)
- Rozenn N. Lemaitre
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle
| | - Paul N. Jensen
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle
| | - Zeneng Wang
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | | | | | - Ina Nemet
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Mary L. Biggs
- Department of Biostatistics, University of Washington, Seattle
| | - Nona Sotoodehnia
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle
- Division of Cardiology, University of Washington, Seattle
| | - Marcia C. de Oliveira Otto
- Division of Epidemiology, Human Genetics and Environmental Science, School of Public Health, The University of Texas Health Science Center at Houston
| | - Bruce M. Psaty
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle
- Department of Epidemiology, University of Washington, Seattle
- Kaiser Permanente Washington Health Research Institute, Seattle
| | | | - Stanley L. Hazen
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
- Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio
| | - Dariush Mozaffarian
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts
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11
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Kokozheva M, Mardanov B, Mamedov M. Acute coronary syndrome in diabetes mellitus: features of pathogenesis, course and therapy. PROFILAKTICHESKAYA MEDITSINA 2021; 24:89. [DOI: 10.17116/profmed20212402189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/10/2024]
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12
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Yoon H. Relationship between Metabolic Syndrome, Metabolic Syndrome Score, Insulin Resistance and Beta Cell Function in Korean Adults with Obesity. KOREAN JOURNAL OF CLINICAL LABORATORY SCIENCE 2020. [DOI: 10.15324/kjcls.2020.52.4.327] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Affiliation(s)
- Hyun Yoon
- Department of Clinical Laboratory Science, Wonkwang Health Science University, Iksan, Korea
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13
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Prentki M, Peyot ML, Masiello P, Madiraju SRM. Nutrient-Induced Metabolic Stress, Adaptation, Detoxification, and Toxicity in the Pancreatic β-Cell. Diabetes 2020; 69:279-290. [PMID: 32079704 DOI: 10.2337/dbi19-0014] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 12/20/2019] [Indexed: 11/13/2022]
Abstract
Paraphrasing the Swiss physician and father of toxicology Paracelsus (1493-1541) on chemical agents used as therapeutics, "the dose makes the poison," it is now realized that this aptly applies to the calorigenic nutrients. The case here is the pancreatic islet β-cell presented with excessive levels of nutrients such as glucose, lipids, and amino acids. The short-term effects these nutrients exert on the β-cell are enhanced insulin biosynthesis and secretion and changes in glucose sensitivity. However, chronic fuel surfeit triggers additional compensatory and adaptive mechanisms by β-cells to cope with the increased insulin demand or to protect itself. When these mechanisms fail, toxicity due to the nutrient surplus ensues, leading to β-cell dysfunction, dedifferentiation, and apoptosis. The terms glucotoxicity, lipotoxicity, and glucolipotoxicity have been widely used, but there is some confusion as to what they mean precisely and which is most appropriate for a given situation. Here we address the gluco-, lipo-, and glucolipo-toxicities in β-cells by assessing the evidence both for and against each of them. We also discuss potential mechanisms and defend the view that many of the identified "toxic" effects of nutrient excess, which may also include amino acids, are in fact beneficial adaptive processes. In addition, candidate fuel-excess detoxification pathways are evaluated. Finally, we propose that a more general term should be used for the in vivo situation of overweight-associated type 2 diabetes reflecting both the adaptive and toxic processes to mixed calorigenic nutrients excess: "nutrient-induced metabolic stress" or, in brief, "nutri-stress."
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Affiliation(s)
- Marc Prentki
- Departments of Nutrition and Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada
| | - Marie-Line Peyot
- Departments of Nutrition and Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada
| | - Pellegrino Masiello
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - S R Murthy Madiraju
- Departments of Nutrition and Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada
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Liu Y, Chen T, Zhou F, Mu D, Liu S. Interleukin-38 increases the insulin sensitivity in children with the type 2 diabetes. Int Immunopharmacol 2020; 82:106264. [PMID: 32087495 DOI: 10.1016/j.intimp.2020.106264] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 01/27/2020] [Accepted: 01/27/2020] [Indexed: 12/15/2022]
Abstract
The prevalence of type 2 diabetes mellitus (DM) is increasing in the children population. It is well known that inflammation contributes to the type 2 DM pathogenesis. Interleukin 38 (IL-38) is one newly identified anti-inflammatory factor. Therefore, we investigated whether the expression level of IL-38 is associated with type 2 DM in the children and the underlying mechanism. Children with recently diagnosed type 2 diabetes mellitus were recruited and studied. The healthy subjects without glucose metabolism abnormalities were used as controls. The IL-38 expression level was determined by quantitative PCR and ELISA (Enzyme-linked immunoassay). Statistic analysis showed that the IL-38 level was significantly associated with type 2 DM and insulin resistance in the children. The patients were then divided into two groups, one group sensitive to insulin therapy while the other resistant to insulin therapy. Data showed that the IL-38 was highly expressed in the group sensitive to insulin therapy. In the mice model, overexpressing the IL-38 could suppress the expression of IL-36, a pro-inflammatory factor, and also the diabetes development. Thus our results showed that higher IL-38 was associated with the increased insulin sensitive in children with type 2 DM and inhibited T2DM development in the mouse model through suppressing the function of IL-36.
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Affiliation(s)
- Ying Liu
- Department of Pediatrics, West China Second Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University), Ministry of Education, Chengdu 610041, Sichuan, China
| | - Tao Chen
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Fangli Zhou
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Dezhi Mu
- Department of Pediatrics, West China Second Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University), Ministry of Education, Chengdu 610041, Sichuan, China.
| | - Shanling Liu
- Department of Pediatrics, West China Second Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University), Ministry of Education, Chengdu 610041, Sichuan, China.
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15
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Chen N, Muhammad IF, Li Z, Nilsson PM, Borné Y. Sex-Specific Associations of Circulating Uric Acid with Risk of Diabetes Incidence: A Population-Based Cohort Study from Sweden. Diabetes Metab Syndr Obes 2020; 13:4323-4331. [PMID: 33209045 PMCID: PMC7669519 DOI: 10.2147/dmso.s273387] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 09/25/2020] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE To explore the longitudinal, as well as sex-specific, associations between circulating uric acid (UA) and diabetes incidence. METHODS A cohort study of the Malmö Diet Cancer-cardiovascular Cohort (Malmö, Sweden) consisting of 3140 individuals without diabetes at baseline, was followed up until the end of 2018. Incident diabetes cases were identified by linking to local and national diabetes registers. Cox proportional hazard regression was used to assess plasma UA levels in relation to diabetes incidence with adjustment for established confounders. RESULTS At baseline, with increasing levels of UA, subjects were more likely to be older and have significantly higher body mass index, waist circumference, triglycerides, C-reactive protein, fasting glucose and 2-h plasma glucose postoral glucose tolerance test, and lower levels of high-density lipoprotein. During a mean follow-up period of 8.09±2.24 years, 315 (10.0%) participants developed diabetes, and diabetes incidence rates were 7.89, 9.48 and 18.11 per 1000 person-years for subjects in the 1st, 2nd, and 3rd tertiles of UA, respectively (log-rank test: p<0.001). With adjustment for potential confounders, elevated UA levels were significantly associated with increased risks of diabetes incidence, with the adjusted hazard ratio (HR) (95% confidence interval) for per standard deviation increment of UA of 1.22 (1.08-1.39, p=0.002). Compared with the 1st tertile of UA, the 3rd tertile showed significantly increased risk of diabetes incidence with the adjusted HR of 1.74 (1.24-2.45, p=0.002), and there was a significant trend between increasing tertiles of UA and diabetes incidence (trend test: p<0.001). Stratified analyses showed that elevated circulating UA levels were independently associated with increased risks of diabetes incidence in men but not in women, although the interaction between sex and UA was not statistically significant. CONCLUSION Elevated circulating UA was independently associated with increased risk of diabetes incidence, especially for men.
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Affiliation(s)
- Ning Chen
- Department of Endocrinology, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, People’s Republic of China
- Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden
| | | | - Zhibin Li
- Epidemiology Research Unit, The First Affiliated Hospital, Xiamen University, Xiamen, People’s Republic of China
| | - Peter M Nilsson
- Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden
- Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden
| | - Yan Borné
- Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden
- Correspondence: Yan Borné; Ning Chen Email ;
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Use of Blood Lipid Indicators as a Screening Tool of Insulin Resistance among Individuals in Low-Income Country Sides of China: A Multiethnic Region Study. Mediators Inflamm 2019; 2019:3592620. [PMID: 31686981 PMCID: PMC6800908 DOI: 10.1155/2019/3592620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 08/02/2019] [Indexed: 12/01/2022] Open
Abstract
Objective This study is aimed at evaluating the diagnostic value of blood lipid indicators (BLIs) for insulin resistance (IR) among major ethnic groups in Xinjiang, China, to identify the most valuable indicators and appropriate cut-off points for each ethnic group and to lay the foundation for the early detection, diagnosis, and treatment of metabolic diseases in remote rural areas. Methods Overall, 418 Uygurs, 331 Kazakhs, and 220 Hans were randomly included in our study. The homeostasis model assessment was the gold standard for identifying IR. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value, and the nomogram was utilized to analyze the predictive value. The size of the area under the curve (AUC) reflected the accuracy of screening and prediction. Results Differences in races were observed in terms of IR and BLIs, and the Kazakhs had the highest IR level at 5.27 mmol/L. The correlation between IR and BLIs differed among the three races. For the Kazakhs and Hans, all BLIs, except total cholesterol (TC), were correlated to IR. However, for the Uygurs, only the triglyceride (TG) level, TG/high-density lipoprotein cholesterol (HDL-C) ratio, and TC/HDL-C ratio were associated with IR. After further adjustment of confounding factors, these indicators were still correlated to IR. BLIs that independently correlated to IR in the three nationalities had a certain diagnostic value for IR. In terms of the AUC size, the TG level was the highest in Uygurs, the TG/HDL-C ratio was the highest for Kazakhs and Hans, and the corresponding best cut-off points for IR were 1.515, 1.230, and 1.495 mmol/L, respectively. In addition, for each race, when the indicators with a certain diagnostic value were combined, the diagnostic value for IR was higher. Conclusion BLIs had a certain diagnostic value for IR and could be used as a screening tool for IR among Uygurs, Kazakhs, and Hans in Xinjiang. These findings are extremely important for the prevention and treatment of IR and metabolic diseases in remote rural areas.
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Lee KS, Gi MY, Cha JA, Lee JM, Jung SH, Yoon H. The relationship between pulse pressure, insulin resistance, and beta cell function in non-diabetic Korean adults. Prim Care Diabetes 2019; 13:422-429. [PMID: 30862423 DOI: 10.1016/j.pcd.2019.01.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2018] [Revised: 01/16/2019] [Accepted: 01/17/2019] [Indexed: 12/17/2022]
Abstract
AIMS The present study was conducted to assess the association of pulse pressure (PP) with insulin resistance and beta cell function in Korean non-diabetic populations. METHODS This study used the data from the 2015 Korean National Health and Nutrition Examination Survey including 4380 adults, aged 20 or older. RESULTS A multivariate analysis revealed that systolic blood pressure (SBP) (β=0.089, 95% confidence interval [CI], 0.004-0.011; p<0.001), diastolic blood pressure (DBP) (β=-0.057, 95% CI -0.014 to -0.003; p=0.002), and PP (β=0.069, 95% CI 0.004-0.011; p<0.001) were significant factors determining the homeostasis model assessment of insulin resistance (HOMA-IR). SBP (β=0.070, 95% CI, 0.113-0.420; p=0.001), DBP (β=-0.068, 95% CI -0.676 to -0.203; p<0.001), and PP (β=0.050, 95% CI 0.115-0.422; p=0.001) were significant factors determining the homeostasis model assessment of beta cell function (HOMA-B). In the analysis of covariance test, after adjusting for related variables (except age), the quartiles of PP were not associated with HOMA-IR (p=0.191) and were inversely associated with HOMA-B (p<0.001). However, when further adjusting for age, the quartiles of PP were positively associated with both HOMA-IR (p<0.001) and HOMA-B (p=0.027). CONCLUSION PP was positively associated with insulin resistance and beta cell function in non-diabetic Korean adults.
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Affiliation(s)
- Kyu Su Lee
- Department of Radiological Science, Hanlyo University, 94-13, Hallyeodaegil, Gwangyangeup, Gwangyangsi, Jeollanamdo, 57764, South Korea
| | - Mi Young Gi
- Department of Nursing, Christian College of Nursing, 6, Baekseo-ro 70 beongil, Nam-gu, Gwangju, 61662, South Korea
| | - Ju Ae Cha
- Department of Nursing, Chunnam Technouniversity, 113, Daehak-ro, Okgwa-myeon, Gokseong-gun, Jeollanam-do, 57500, South Korea
| | - Jae Min Lee
- Department of Emergency Medical Technology, Gwangju Health University, 73, Bungmun-daero 419beon-gil, Gwangsan-gu, Gwangju, 62287, South Korea
| | - Sun Hee Jung
- Department of Nursing, Kwangju Christian Hospital, 30, Yangnim-ro, Nam-gu, Gwangju, 61660, South Korea
| | - Hyun Yoon
- Department of Biomedical Laboratory Science, Wonkwang Health Science University, 514, Iksan-daero, Iksan-si, Jeollabuk-do, 54538, South Korea.
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Li T, Li H, Li W, Chen S, Feng T, Jiao W, Wu C, Dong J, Li Y, Li S, Feng M, Wei X. Interleukin-37 sensitize the elderly type 2 diabetic patients to insulin therapy through suppressing the gut microbiota dysbiosis. Mol Immunol 2019; 112:322-329. [PMID: 31238287 DOI: 10.1016/j.molimm.2019.06.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 06/12/2019] [Accepted: 06/14/2019] [Indexed: 12/30/2022]
Abstract
OBJECTIVE The morbidity and prevalence of type 2 diabetes mellitus (DM) are increasing in the elderly population. Interleukin 37 (IL-37) play important roles in anti-inflammatory and anti-bacteria immune responses, but its role in the development of type 2 DM in the elderly is unclear. Therefore, we investigated whether IL-37 is associated with type 2 DM in the elderly and the underlying mechanism. METHODS Hospitalized patients (aged 65-95 years) with recently diagnosed type 2 diabetes mellitus were studied retrospectively and compared with healthy subjects without glucose metabolism abnormalities. A diabetic mouse model was established by feeding ob/ob mice (C57BL/6) a high-fat, carbohydrate-free diet. Plasma glucose and insulin levels were determined by glucose oxidase assay and radioimmunoassay, respectively. The IL-37 expression level was determined by real-time PCR, western blot and ELISA (Enzyme-linked immunoassay). RESULTS Statistic analysis showed that the IL-37 level was significantly associated with type 2 DM and insulin resistance in the elderly. The patients were then divided into insulin therapy sensitive and resistant group according to their response to insulin therapy. Data showed that the IL-37 was highly expressed in the insulin therapy sensitive group. And this was related to the less severe gut microbiota dysbiosis. In the mice model, overexpressing the IL-37 could suppress the gut microbiota dysbiosis and also the diabetes development. CONCLUSION Thus our results showed that higher IL-37 was associated with increased insulin sensitive in elderly type 2 DM patients through suppressing the gut microbiota dysbiosis.
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Affiliation(s)
- Tianyi Li
- Department of Elderly Endocrinology, The First Affiliated Hospital of Zhengzhou University, 450000, Zhengzhou, Henan Province, PR China.
| | - Hua Li
- Department of Elderly Endocrinology, The First Affiliated Hospital of Zhengzhou University, 450000, Zhengzhou, Henan Province, PR China.
| | - Weifang Li
- Department of Elderly Endocrinology, The First Affiliated Hospital of Zhengzhou University, 450000, Zhengzhou, Henan Province, PR China.
| | - Sufang Chen
- Department of Elderly Endocrinology, The First Affiliated Hospital of Zhengzhou University, 450000, Zhengzhou, Henan Province, PR China.
| | - Tao Feng
- Department of Elderly Endocrinology, The First Affiliated Hospital of Zhengzhou University, 450000, Zhengzhou, Henan Province, PR China.
| | - Wenjun Jiao
- Department of Elderly Endocrinology, The First Affiliated Hospital of Zhengzhou University, 450000, Zhengzhou, Henan Province, PR China.
| | - Cong Wu
- Department of Elderly Endocrinology, The First Affiliated Hospital of Zhengzhou University, 450000, Zhengzhou, Henan Province, PR China.
| | - Jie Dong
- Department of Elderly Endocrinology, The First Affiliated Hospital of Zhengzhou University, 450000, Zhengzhou, Henan Province, PR China.
| | - Yuanyuan Li
- Department of Elderly Endocrinology, The First Affiliated Hospital of Zhengzhou University, 450000, Zhengzhou, Henan Province, PR China.
| | - Sujun Li
- Department of Elderly Endocrinology, The First Affiliated Hospital of Zhengzhou University, 450000, Zhengzhou, Henan Province, PR China.
| | - Ming Feng
- Department of Elderly Endocrinology, The First Affiliated Hospital of Zhengzhou University, 450000, Zhengzhou, Henan Province, PR China.
| | - Xiaowen Wei
- Department of Elderly Endocrinology, The First Affiliated Hospital of Zhengzhou University, 450000, Zhengzhou, Henan Province, PR China.
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Danet-Lamasou M, Pérès K, Matharan F, Berr C, Carrière I, Tzourio C, Delcourt C, Bourdel-Marchasson I. Near Visual Impairment Incidence in Relation to Diabetes in Older People: The Three-Cities Study. J Am Geriatr Soc 2018; 66:699-705. [DOI: 10.1111/jgs.15266] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Marie Danet-Lamasou
- Clinical Gerontology; Centre Hospitalier Universitaire of Bordeaux; Pessac France
- Unité de Formation et de Recherche Medicine; University of Bordeaux; Bordeaux France
- Unité de Formation et de Recherche 5536; Résonance Magnétique des Systèmes Biologiques; Centre National de la Recherche Scientifique; Bordeaux France
| | - Karine Pérès
- Institut de Santé Publique d'Epidémiologie et de Développement; University of Bordeaux; Bordeaux France
- U1219; Bordeaux Population Health Research Center; Institut National de la Santé et de la Recherche Médicale; Bordeaux France
| | - Fanny Matharan
- Institut de Santé Publique d'Epidémiologie et de Développement; University of Bordeaux; Bordeaux France
- U1219; Bordeaux Population Health Research Center; Institut National de la Santé et de la Recherche Médicale; Bordeaux France
| | - Claudine Berr
- U1061; Institut National de la Santé et de la Recherche Médicale; Montpellier France
- University of Montpellier; Montpellier France
| | - Isabelle Carrière
- U1061; Institut National de la Santé et de la Recherche Médicale; Montpellier France
- University of Montpellier; Montpellier France
| | - Christophe Tzourio
- Institut de Santé Publique d'Epidémiologie et de Développement; University of Bordeaux; Bordeaux France
- U1219; Bordeaux Population Health Research Center; Institut National de la Santé et de la Recherche Médicale; Bordeaux France
| | - Cécile Delcourt
- Institut de Santé Publique d'Epidémiologie et de Développement; University of Bordeaux; Bordeaux France
- U1219; Bordeaux Population Health Research Center; Institut National de la Santé et de la Recherche Médicale; Bordeaux France
| | - Isabelle Bourdel-Marchasson
- Clinical Gerontology; Centre Hospitalier Universitaire of Bordeaux; Pessac France
- Unité de Formation et de Recherche 5536; Résonance Magnétique des Systèmes Biologiques; Centre National de la Recherche Scientifique; Bordeaux France
- Résonance Magnétique des Systèmes Biologiques; Unite Mixte de Recherche5536; University of Bordeaux; Bordeaux France
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20
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Lee YM, Jacobs Jr. DR, Lee DH. Persistent Organic Pollutants and Type 2 Diabetes: A Critical Review of Review Articles. Front Endocrinol (Lausanne) 2018; 9:712. [PMID: 30542326 PMCID: PMC6277786 DOI: 10.3389/fendo.2018.00712] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 11/12/2018] [Indexed: 12/22/2022] Open
Abstract
Low dose persistent organic pollutants (POPs) have emerged as a new risk for type 2 diabetes (T2D). Despite substantial evidence from human and experimental studies, there are several critical issues which have not been properly addressed by POPs researchers. First, as POPs exist as mixtures, findings about POPs from human studies should be interpreted from the viewpoint of lipophilic chemical mixtures which include both measured and unmeasured POPs. Second, as POPs can directly reduce insulin secretion of beta cells, the role of POPs may be more prominent in the development of beta-cell dysfunction-dominant T2D rather than insulin resistance-dominant T2D. Third, there are multidimensional interrelationships between POPs and adipose tissue. Even though POPs are now considered as a new risk factor for T2D, independent of obesity, POPs and obesity are mechanistically linked to each other. POPs are involved in key mechanisms linking obesity and T2D, such as chronic inflammation of adipose tissue and lipotoxicity with ectopic fat accumulation. Also, POPs can explain puzzling human findings which suggest benefits of obesity because healthy adipose tissue can be protective by reducing the amount of POPs reaching other organs. Fourth, non-linear dose-response relationships between POPs and T2D are biologically possible. Although POPs are well-known endocrine disrupting chemicals (EDCs), mitochondrial dysfunction may be a more plausible mechanism due to unpredictability of EDC mixtures. As adipose tissue plays a role as an internal exposure source of POPs, how to manage POPs inside us may be essential to protect against harms of POPs.
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Affiliation(s)
- Yu-Mi Lee
- Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - David R. Jacobs Jr.
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, United States
| | - Duk-Hee Lee
- Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, DaeguSouth Korea
- *Correspondence: Duk-Hee Lee
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21
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Lee YM, Ha CM, Kim SA, Thoudam T, Yoon YR, Kim DJ, Kim HC, Moon HB, Park S, Lee IK, Lee DH. Low-Dose Persistent Organic Pollutants Impair Insulin Secretory Function of Pancreatic β-Cells: Human and In Vitro Evidence. Diabetes 2017; 66:2669-2680. [PMID: 28720696 DOI: 10.2337/db17-0188] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 07/13/2017] [Indexed: 11/13/2022]
Abstract
Low-dose persistent organic pollutants (POPs), especially organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), have emerged as a new risk factor for type 2 diabetes. We evaluated whether chronic exposure to low-dose POPs affects insulin secretory function of β-cells in humans and in vitro cells. Serum concentrations of OCPs and PCBs were measured in 200 adults without diabetes. Mathematical model-based insulin secretion indices were estimated by using a 2-h seven-sample oral glucose tolerance test. Insulin secretion by INS-1E β-cells was measured after 48 h of treatment with three OCPs or one PCB mixture. Static second-phase insulin secretion significantly decreased with increasing serum concentrations of OCPs. Adjusted means were 63.2, 39.3, 44.1, 39.3, 39.7, and 22.3 across six categories of a summary measure of OCPs (Ptrend = 0.02). Dynamic first-phase insulin secretion remarkably decreased with increasing concentrations of OCPs among only insulin-sensitive individuals (Ptrend = 0.02); the insulin levels among individuals with high OCPs were ∼30% of those with low OCPs. Compared with OCPs, PCBs showed weaker associations. The decreased insulin secretion by INS-1E β-cells was observed for even 1 pmol/L OCP. The data from human and in vitro cell experiments suggest that chronic exposure to low-dose POPs, especially OCPs, can induce pancreatic β-cell dysfunction.
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Affiliation(s)
- Yu-Mi Lee
- Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Chae-Myeong Ha
- Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Republic of Korea
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea
| | - Se-A Kim
- Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Republic of Korea
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea
| | - Themis Thoudam
- Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Republic of Korea
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea
| | - Young-Ran Yoon
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea
- Department of Biomedical Science, School of Medicine, Kyungpook National University and Hospital, Daegu, Republic of Korea
| | - Dae-Jung Kim
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Hyeon-Chang Kim
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyo-Bang Moon
- Department of Environmental Marine Sciences, College of Science and Technology, Hanyang University, Ansan, Republic of Korea
| | - Sungmi Park
- Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University, Daegu, Republic of Korea
| | - In-Kyu Lee
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea
- Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University, Daegu, Republic of Korea
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Duk-Hee Lee
- Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea
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22
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Climent E, Pérez-Calahorra S, Marco-Benedí V, Plana N, Sánchez R, Ros E, Ascaso JF, Puzo J, Almagro F, Lahoz C, Civeira F, Pedro-Botet J. Effect of LDL cholesterol, statins and presence of mutations on the prevalence of type 2 diabetes in heterozygous familial hypercholesterolemia. Sci Rep 2017; 7:5596. [PMID: 28717233 PMCID: PMC5514105 DOI: 10.1038/s41598-017-06101-6] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 06/07/2017] [Indexed: 11/09/2022] Open
Abstract
Patients with heterozygous familial hypercholesterolemia (HeFH) have been reported to be less vulnerable to type 2 diabetes mellitus (T2DM), although the mechanism is unknown. The aims of the present study were to assess the effects of low density lipoprotein (LDL) cholesterol concentration and the presence of FH-causing mutations on T2DM prevalence in HeFH. Data were collected from the Dyslipidemia Registry of the Spanish Arteriosclerosis Society. Inclusion criteria were definite or probable HeFH in patients aged ≥18 years. T2DM prevalence in HeFH patients was compared with data of the general population. 1732 patients were included. The prevalence of T2DM was lower in patients with HeFH compared with the general population (5.94% vs 9.44%; OR: 0.606, 95% CI 0.486-0.755, p < 0.001). Risk factors for developing T2DM were male sex, age, body mass index, hypertension, baseline triglyceride levels and years on statin therapy. The prevalence of T2DM in HeFH patients was 40% lower than that observed in the general population. Gene mutations and LDL cholesterol concentrations were not risk factors associated with the prevalence of T2DM in patients with HeFH. The prevalence of T2DM in patients with HeFH was 40% lower than in the general population matched for age and sex.
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Affiliation(s)
- Elisenda Climent
- Lipid and Vascular Unit, Department of Endocrinology and Nutrition, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Sofía Pérez-Calahorra
- Lipid Unit. Hospital Universitario Miguel Servet, IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain
| | - Victoria Marco-Benedí
- Lipid Unit. Hospital Universitario Miguel Servet, IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain
| | - Nuria Plana
- Unitat de Medicina Vascular i Metabolisme, Hospital Universitari Sant Joan, Institut d´Investigació Sanitaria Pere Virgili (IISPV), Reus, Tarragona, Spain
| | - Rosa Sánchez
- Lipid Unit, Servicio de Endocrinología y Nutrición, Hospital Universitario Insular de Gran Canarias, Instituto Universitario de Investigaciones Biomédicas y Sanitarias de la Universidad de Las Palmas de Gran Canarias, Las Palmas, Spain
| | - Emilio Ros
- Lipid Clinic, Endocrinology and Nutrition Service, Institut d'Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona and CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Juan F Ascaso
- Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Universitat de Valencia, Valencia, Spain
| | - Jose Puzo
- Lipid Unit. Hospital San Jorge, Huesca, Spain
| | | | - Carlos Lahoz
- Atherosclerosis Unit, Internal Medicine Department, Hospital Carlos III, Madrid, Spain
| | - Fernando Civeira
- Lipid Unit. Hospital Universitario Miguel Servet, IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain
| | - Juan Pedro-Botet
- Lipid and Vascular Unit, Department of Endocrinology and Nutrition, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Zhao Q, Laukkanen JA, Li Q, Li G. Body mass index is associated with type 2 diabetes mellitus in Chinese elderly. Clin Interv Aging 2017; 12:745-752. [PMID: 28496312 PMCID: PMC5422331 DOI: 10.2147/cia.s130014] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background There is limited information on the association between metabolic syndrome components including body mass index (BMI) and type 2 diabetes mellitus in elderly Chinese population. Therefore, we investigated whether components of metabolic syndrome are associated with type 2 diabetes mellitus in elderly. Methods A total of 479 hospitalized patients (aged 65–95 years) with recently diagnosed type 2 diabetes mellitus were studied retrospectively in a cross-sectional study and compared with 183 subjects with prediabetes and 62 subjects without glucose metabolism abnormalities. Results BMI (24.69±3.59 versus 23.92±3.08 and 23.56±3.25 kg/m2), blood pressure, cholesterol, triglyceride, liver enzymes and prevalence of fatty liver were higher in patients with type 2 diabetes mellitus as compared with elderly subjects with prediabetes or normal glucose metabolism separately (all P<0.05). Multivariable regression analysis showed that BMI was associated positively with insulin resistance and inversely with insulin sensitivity in type 2 diabetes mellitus group (all P<0.05). Conclusion Higher BMI was associated with increased insulin resistance and decreased insulin sensitivity in elderly Asian population with type 2 diabetes mellitus.
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Affiliation(s)
- Qianping Zhao
- Division of Cardiology, Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Jari A Laukkanen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.,Department of Medicine, Central Finland Central Hospital, Jyväskylä, Finland
| | - Qifu Li
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Gang Li
- Division of Cardiology, Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
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24
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Azemati B, Rajaram S, Jaceldo-Siegl K, Sabate J, Shavlik D, Fraser GE, Haddad EH. Animal-Protein Intake Is Associated with Insulin Resistance in Adventist Health Study 2 (AHS-2) Calibration Substudy Participants: A Cross-Sectional Analysis. Curr Dev Nutr 2017; 1:e000299. [PMID: 29955699 PMCID: PMC5998345 DOI: 10.3945/cdn.116.000299] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Revised: 01/27/2017] [Accepted: 03/04/2017] [Indexed: 11/14/2022] Open
Abstract
Background: High intakes of total and animal protein are associated with the risk of type 2 diabetes (T2D). The influence of protein type on insulin resistance, a key precursor of T2D, has not been extensively studied. Objective: The aim of this study was to determine the associations between dietary total, animal, and plant protein intakes as well as the animal-to-plant protein (AP) intake ratio with insulin resistance in middle-aged and older adults. Methods: This was a cross-sectional analysis in 548 participants (mean ± SD age: 66.2 ± 13.7 y) from the calibration substudy of the AHS-2 (Adventist Health Study 2) cohort. Participants consumed diets with a low AP intake ratio. Dietary intakes of total and particular types of protein were calculated from six 24-h dietary recalls. Participants completed a self-administered questionnaire on demographic, lifestyle, health, diet intake, and physical activity characteristics. Anthropometric variables including weight, height, and waist circumference were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated by using fasting serum glucose and insulin. Multiple linear regression models were used to test the relations between total and specific protein intakes with insulin resistance. Results: The ranges of dietary intakes of animal and plant protein and the AP intake ratio were 0.4-87.4 and 14.0-79.2 g/d and 0.02-4.43, respectively. Dietary intakes per 10-g/d increments of total protein (β: 0.11; 95% CI: 0.02, 0.21) and animal protein (β: 0.11; 95% CI: 0.01, 0.20) and the AP intake ratio (β: 1.82; 95% CI: 0.80, 2.84) were positively related to HOMA-IR. Plant protein was not significantly related to insulin resistance. Conclusion: Total and animal protein intakes and the AP intake ratio were positively associated with HOMA-IR in adults with relatively a low intake of animal protein and a high consumption of plant protein.
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Affiliation(s)
- Bahar Azemati
- Center for Nutrition, Healthy Lifestyle, and Disease Prevention
| | - Sujatha Rajaram
- Center for Nutrition, Healthy Lifestyle, and Disease Prevention
| | | | - Joan Sabate
- Center for Nutrition, Healthy Lifestyle, and Disease Prevention
| | - David Shavlik
- Center for Community Resilience, School of Public Health, Loma Linda University, Loma Linda, CA
| | - Gary E Fraser
- Center for Nutrition, Healthy Lifestyle, and Disease Prevention
| | - Ella H Haddad
- Center for Nutrition, Healthy Lifestyle, and Disease Prevention
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25
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Forbes A, Murrells T, Sinclair AJ. Examining factors associated with excess mortality in older people (age ≥ 70 years) with diabetes - a 10-year cohort study of older people with and without diabetes. Diabet Med 2017; 34:387-395. [PMID: 27087619 DOI: 10.1111/dme.13132] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/11/2016] [Indexed: 12/28/2022]
Abstract
AIMS To compare all-cause mortality in older people with or without diabetes and consider the associated risk of comorbidity and polypharmacy. METHODS A 10-year cohort study using data from the Health Innovation Network database (2003-2013) comparing mortality in people aged ≥ 70 years with diabetes (DM cohort) (n = 35 717) and without diabetes (No DM cohort) (n = 307 918). RESULTS The mean age of the DM cohort was 78.1 ± 5.8 years vs. 79.0 ± 6.3 years in the No DM cohort. Mean diabetes duration was 8.2 ± 8.1 years, and 30% had diabetes for > 10 years. The DM cohort had a greater comorbidity load and people in this cohort were prescribed more therapies than the No DM cohort. The 5- and 10-year survival rates were lower in the DM cohort at 64% and 39%, respectively, compared with 72% and 50% in the No DM cohort. The excess mortality in the DM cohort was greatest in those aged < 75 years with longer duration diabetes, the relative hazard for mortality was higher in females. Although comorbidity and polypharmacy were associated with increased mortality risk in the DM cohort, this risk was lower compared with the No DM cohort. The hazard ratios (95% confidence interval) for comorbidities > 4 and medicines ≥ 7 were 1.29 (1.19 to 1.41) and 1.34 (1.25 to 1.43) in the DM cohort and 1.63 (1.57 to 1.70) and 1.48 (1.40 to 1.56) in the No DM cohort, respectively. CONCLUSIONS There is significant excess mortality in older people with diabetes, which is unexplained by comorbidity or polypharmacy. This excess is greatest in the younger old with longer disease duration, suggesting that it may be related to the effect of diabetes exposure.
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Affiliation(s)
- A Forbes
- Florence Nightingale Faculty of Nursing and Midwifery, King's College London, London
| | - T Murrells
- Florence Nightingale Faculty of Nursing and Midwifery, King's College London, London
| | - A J Sinclair
- Diabetes Frail and the University of Aston, Birmingham, UK
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26
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Sheikh BY. The role of prophetic medicine in the management of diabetes mellitus: A review of literature. J Taibah Univ Med Sci 2016. [DOI: 10.1016/j.jtumed.2015.12.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
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Sung KC, Park HY, Kim MJ, Reaven G. Metabolic markers associated with insulin resistance predict type 2 diabetes in Koreans with normal blood pressure or prehypertension. Cardiovasc Diabetol 2016; 15:47. [PMID: 27001495 PMCID: PMC4802716 DOI: 10.1186/s12933-016-0368-7] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Accepted: 03/15/2016] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Questions remain as to the association between essential hypertension and increased incidence of type 2 diabetes (T2DM). The premise of this analysis is that insulin resistance/compensatory hyperinsulinemia is a major predictor of T2DM, and the greater the prevalence of insulin resistance within any population, normotensive or hypertensive, the more likely T2DM will develop. The hypothesis to be tested is that surrogate estimates of insulin resistance will predict incident T2DM to a significant degree in persons with normal blood pressure or prehypertension. METHODS Analysis of data from a population-based survey of 10, 038 inhabitants of rural and urban areas of Korea, ≥40 years-old, initiated in 2001, with measures of demographic and metabolic characteristics at baseline and 8-years later. Participants were classified as having normal blood pressure or prehypertension, and three simple manifestations of insulin resistance related to the pathophysiology of T2DM used to predict incident T2DM: (1) glycemia (plasma glucose concentration 2-hour after 75 g oral glucose challenge = 2-hour PG); (2) hyperinsulinemia (plasma insulin concentration 2-hour after 75 g oral glucose challenge = 2-hour PI); and (3) dyslipidemia (ratio of fasting plasma triglyceride/high/density lipoprotein cholesterol concentration = TG/HDL-C ratio). RESULTS Fully adjusted hazard ratios (HR, 95 % CI) for incident T2DM were highest (P < 0.001) in the quartile of individuals with the highest 2-hour PG concentrations, ranging from 5.84 (3.37-10.1) in women with prehypertension to 12.2 (7.12-21.00) in men with normal blood pressure. T2DM also developed to a significantly greater degree in subjects within the highest quartile of TG/HDL-C ratios, with HRs varying from 2.91 (1.63-2.58) in women with prehypertension (P < 0.001) to 1.77 (1.12-2.81, P < 0.05) in men with prehypertension. The least predictive index of insulin resistance was the 2-hour PI concentration. Subjects with normal blood pressure in the highest quartile of 2-hour PI concentrations were significantly associated with incident T2DM, with HRs of 1.5 (1.02-2.20, P = 0.25) and 2.02 (1.35-3.02, P < 0.001), in men and women, respectively. Finally, incidence of T2DM in the highest quartile was somewhat greater in patients with prehypertension, irrespective of predictor. CONCLUSIONS Metabolic variables associated with insulin resistance (glycemia, insulinemia, and dyslipidemia) predict the development of T2DM in patients with either normal blood pressure or prehypertension.
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Affiliation(s)
- Ki-Chul Sung
- />Division of Cardiology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, #108, Pyung Dong, Jongro-Ku, Seoul, 110-746 Republic of Korea
| | - Hyun-Young Park
- />Division of Cardiovascular and Rare Diseases, Center for Biomedical Science, Korea National Institute of Health, 187 Osongsaengmyeng 2-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 361-951 Republic of Korea
| | - Min-Ju Kim
- />Division of Cardiovascular and Rare Diseases, Center for Biomedical Science, Korea National Institute of Health, 187 Osongsaengmyeng 2-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 361-951 Republic of Korea
| | - Gerald Reaven
- />Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305 USA
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Lipska KJ, Krumholz H, Soones T, Lee SJ. Polypharmacy in the Aging Patient: A Review of Glycemic Control in Older Adults With Type 2 Diabetes. JAMA 2016; 315:1034-45. [PMID: 26954412 PMCID: PMC4823136 DOI: 10.1001/jama.2016.0299] [Citation(s) in RCA: 170] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
IMPORTANCE There is substantial uncertainty about optimal glycemic control in older adults with type 2 diabetes mellitus. OBSERVATIONS Four large randomized clinical trials (RCTs), ranging in size from 1791 to 11,440 patients, provide the majority of the evidence used to guide diabetes therapy. Most RCTs of intensive vs standard glycemic control excluded adults older than 80 years, used surrogate end points to evaluate microvascular outcomes and provided limited data on which subgroups are most likely to benefit or be harmed by specific therapies. Available data from randomized clinical trials suggest that intensive glycemic control does not reduce major macrovascular events in older adults for at least 10 years. Furthermore, intensive glycemic control does not lead to improved patient-centered microvascular outcomes for at least 8 years. Data from randomized clinical trials consistently suggest that intensive glycemic control immediately increases the risk of severe hypoglycemia 1.5- to 3-fold. Based on these data and observational studies, for the majority of adults older than 65 years, the harms associated with a hemoglobin A1c (HbA1c) target lower than 7.5% or higher than 9% are likely to outweigh the benefits. However, the optimal target depends on patient factors, medications used to reach the target, life expectancy, and patient preferences about treatment. If only medications with low treatment burden and hypoglycemia risk (such as metformin) are required, a lower HbA1c target may be appropriate. If patients strongly prefer to avoid injections or frequent fingerstick monitoring, a higher HbA1c target that obviates the need for insulin may be appropriate. CONCLUSIONS AND RELEVANCE High-quality evidence about glycemic treatment in older adults is lacking. Optimal decisions need to be made collaboratively with patients, incorporating the likelihood of benefits and harms and patient preferences about treatment and treatment burden. For the majority of older adults, an HbA1c target between 7.5% and 9% will maximize benefits and minimize harms.
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Affiliation(s)
- Kasia J Lipska
- Department of Internal Medicine, Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut
| | - Harlan Krumholz
- Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Connecticut3Section of Cardiovascular Medicine and the Robert Wood Johnson Foundation Clinical Scholars Program, Yale School of Medicine, New Haven, Connecticut4Department of
| | - Tacara Soones
- Department of Geriatrics and Palliative Medicine; Icahn School of Medicine at Mount Sinai; New York
| | - Sei J Lee
- Division of Geriatrics, Department of Medicine, University of California, San Francisco7San Francisco VA Medical Center, California
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A novel cobiotic-based preventive approach against high-fat diet-induced adiposity, nonalcoholic fatty liver and gut derangement in mice. Int J Obes (Lond) 2015; 40:487-96. [PMID: 26395746 DOI: 10.1038/ijo.2015.197] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2015] [Revised: 08/14/2015] [Accepted: 09/03/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND High-fat diets (HFDs) induce systemic inflammation, gut microbial derangements and disturb metabolic homeostasis, resulting in weight gain, insulin resistance and nonalcoholic fatty liver (NAFL). Numerous antioxidants and prebiotic/probiotics per se may prevent HFD-associated comorbidities, but there are no reports related to their combination. OBJECTIVE In the present study, we aim to evaluate a cobiotic combination of lycopene (antioxidant) and isomalto-oligosaccharides (IMOs, a prebiotic) for prevention of HFD-induced alterations. DESIGN Male Swiss albino mice were fed either normal pellet diet (NPD) or HFD and lycopene (5 and 10 mg kg(-1)), IMOs (0.5 and 1 g kg(-1)) or their combination for 12 weeks. Systemic adiposity, glucose tolerance, insulin sensitivity, feeding regulators in hypothalamus, hepatosteatosis and liver inflammation, cecal short chain fatty acids (SCFAs), serum inflammatory cytokines, gut morphology and alterations in selected gut microbes were studied. RESULTS Lycopene, IMOs and their combination prevented weight gain, adiposity, improved adipose tissue fat mobilization and reduced insulin resistance. Hypothalamic orexigenic and anorectic genes have also been modulated by these treatments. Dietary interventions prevented NAFL-like symptoms and improved glucose homeostasis. Improvement in selected gut microbial abundance and SCFA concentration along with reduced systemic inflammation, metabolic endotoxemia and improved ileal and colonic health were observed in mice supplemented with lycopene, IMOs and their combination. Interestingly, cobiotic combination synergistically improved many of the HFD-induced alterations. CONCLUSION The present work provide evidence that new approach based on cobiotic combination (antioxidant plus prebiotic) can be employed to develop novel class of functional foods for their application against HFD-associated pathological complications.
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Zhou M, Li Z, Min R, Dong Y, Sun Q, Li Y. Log (TG)/HDL-C ratio as a predictor of decreased islet beta cell function in patients with type 2 diabetes: 6-year cohort study. J Diabetes 2015; 7:689-98. [PMID: 25327383 DOI: 10.1111/1753-0407.12229] [Citation(s) in RCA: 20] [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: 03/24/2014] [Revised: 07/25/2014] [Accepted: 09/25/2014] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND The aim of the present study was to explore whether the triglyceride to high density lipoprotein cholesterol ratio [log (TG)/HDL-C] and peripheral blood leukocytes DNA telomere length could predict future islet beta cell function decreased in Chinese type 2 diabetes mellitus (T2DM) during a 6-year cohort. METHODS Sixty T2DM patients (without insulin treatment at baseline) were included in the 6-year cohort study. Peripheral blood leukocytes DNA telomere length, HbA1c, blood lipid profile, fatty fat acid, glucose, insulin and C peptide (3 h after a mixed meal) were determined. Delta C peptide area under curve (Delta CP AUC) was used to reflect change in beta cell secretion function (Delta CP AUC = baseline CP AUC - CP AUC after 6 years). Subjects were divided into slow decrease of beta cell function group (Delta CP AUCslow group) and fast decrease group (Delta CP AUCfast group) according to median of Delta CP AUC. Baseline demographic characteristics, clinical variables between two groups were compared. Correlations between baseline data and Delta CP AUC were analyzed. RESULTS Baseline log (TG)/HDL-C was positively correlated with Delta CP AUC (r = 0.306, P = 0.027); log (TG)/HDL-C in Delta CP AUCfast group was higher than that in Delta CP AUCslow group (0.103 ± 0.033 vs 0.083 ± 0.030, P = 0.027). There was no significant difference in DNA telomere length between the two groups. Change in DNA telomere length over 6 years was not significantly correlated with baseline blood lipid. CONCLUSIONS In Chinese T2DM patients, high baseline log (TG)/HDL-C ratio predicts fast progression of islet beta cell dysfunction. It may be a simple index to predict progression speed of islet beta cell dysfunction.
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Affiliation(s)
- Meicen Zhou
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Zengyi Li
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Rui Min
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Yaxiu Dong
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Qi Sun
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Yuxiu Li
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
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Wang Q, Imamura F, Ma W, Wang M, Lemaitre RN, King IB, Song X, Biggs ML, Delaney JA, Mukamal KJ, Djousse L, Siscovick DS, Mozaffarian D. Circulating and dietary trans fatty acids and incident type 2 diabetes in older adults: the Cardiovascular Health Study. Diabetes Care 2015; 38:1099-107. [PMID: 25784660 PMCID: PMC4439533 DOI: 10.2337/dc14-2101] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Accepted: 03/01/2015] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To investigate the effects of trans fatty acids (TFAs) on type 2 diabetes mellitus (DM) by specific TFA subtype or method of assessment. RESEARCH DESIGN AND METHODS In the Cardiovascular Health Study, plasma phospholipid trans (t)-16:1n9, t-18:1, and cis (c)/t-, t/c-, and t/t-18:2 were measured in blood drawn from 2,919 adults aged 74 ± 5 years and free of prevalent DM in 1992. Dietary TFA was estimated among 4,207 adults free of prevalent DM when dietary questionnaires were initially administered in 1989 or 1996. Incident DM was defined through 2010 by medication use or blood glucose levels. Risks were assessed by Cox proportional hazards. RESULTS In biomarker analyses, 287 DM cases occurred during 30,825 person-years. Both t-16:1n9 (extreme quartile hazard ratio 1.59 [95% CI 1.04-2.42], P-trend = 0.04) and t-18:1 (1.91 [1.20-3.03], P-trend = 0.01) levels were associated with higher incident DM after adjustment for de novo lipogenesis fatty acids. In dietary analyses, 407 DM cases occurred during 50,105 person-years. Incident DM was positively associated with consumption of total TFAs (1.38 [1.03-1.86], P-trend = 0.02), t-18:1 (1.32 [1.00-1.76], P-trend = 0.04), and t-18:2 (1.41 [1.05-1.89], P-trend = 0.02). After further adjustment for other dietary habits, however, the associations of estimated dietary TFA with DM were attenuated, and only nonsignificant positive trends remained. CONCLUSIONS Among older adults, plasma phospholipid t-16:1n9 and t-18:1 levels were positively related to DM after adjustment for de novo lipogenesis fatty acids. Estimated dietary TFA was not significantly associated with DM. These findings highlight the need for further observational, interventional, and experimental studies of the effects TFA on DM.
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Affiliation(s)
- Qianyi Wang
- Department of Epidemiology, Harvard School of Public Health, Boston, MA
| | - Fumiaki Imamura
- Medical Research Council Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, U.K
| | - Wenjie Ma
- Department of Epidemiology, Harvard School of Public Health, Boston, MA
| | - Molin Wang
- Department of Biostatistics, Harvard School of Public Health, Boston, MA
| | - Rozenn N Lemaitre
- Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA
| | - Irena B King
- Department of Internal Medicine, University of New Mexico, Albuquerque, NM
| | - Xiaoling Song
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Mary L Biggs
- Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, WA
| | - Joseph A Delaney
- Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA
| | - Kenneth J Mukamal
- Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA
| | - Luc Djousse
- Division of Aging, Brigham and Women's Hospital, Boston, MA Boston Veterans Affairs Healthcare System, Boston, MA
| | | | - Dariush Mozaffarian
- Department of Epidemiology, Harvard School of Public Health, Boston, MA Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA
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Abstract
Diabetes in ageing communities imposes a substantial personal and public health burden by virtue of its high prevalence, its capacity to cause disabling vascular complications, the emergence of new non-vascular complications, and the effects of frailty. In this Review, we examine the current state of knowledge about diabetes in older people (aged ≥ 75 years) and discuss how recognition of the effect of frailty and disability is beginning to lead to new management approaches. A multidimensional and multidisciplinary assessment process is essential to obtain information on medical, psychosocial, and functional capabilities, and also on how impairments of these functions could limit activities. Major aims of diabetes care include maintenance of independence, functional status, and quality of life by reduction of symptom and medicine burden, and active identification of risks. Linking of therapeutic targets to individual functional status is mandatory and very tight glucose control is often not necessary. Hypoglycaemia remains an important avoidable iatrogenic event. Quality diabetes care in older people remains an important challenge for health professionals.
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Affiliation(s)
- Alan Sinclair
- Diabetes Frail, Hampton Lovett, Droitwich, Worcestershire, UK.
| | - Trisha Dunning
- Centre for Nursing and Allied Health Research at Deakin University, VIC, Australia; Barwon Health, VIC, Australia
| | - Leocadio Rodriguez-Mañas
- Department of Geriatrics, Hospital Universitario de Getafe, Getafe, Madrid, Spain; School of Health Sciences, Universidad Europea de Madrid, Madrid, Spain
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Kim JY, Lee DY, Lee YJ, Park KJ, Kim KH, Kim JW, Kim WH. Chronic alcohol consumption potentiates the development of diabetes through pancreatic β-cell dysfunction. World J Biol Chem 2015; 6:1-15. [PMID: 25717351 PMCID: PMC4317634 DOI: 10.4331/wjbc.v6.i1.1] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2014] [Revised: 10/29/2014] [Accepted: 12/10/2014] [Indexed: 02/05/2023] Open
Abstract
Chronic ethanol consumption is well established as a major risk factor for type-2 diabetes (T2D), which is evidenced by impaired glucose metabolism and insulin resistance. However, the relationships between alcohol consumption and the development of T2D remain controversial. In particular, the direct effects of ethanol consumption on proliferation of pancreatic β-cell and the exact mechanisms associated with ethanol-mediated β-cell dysfunction and apoptosis remain elusive. Although alcoholism and alcohol consumption are prevalent and represent crucial public health problems worldwide, many people believe that low-to-moderate ethanol consumption may protect against T2D and cardiovascular diseases. However, the J- or U-shaped curves obtained from cross-sectional and large prospective studies have not fully explained the relationship between alcohol consumption and T2D. This review provides evidence for the harmful effects of chronic ethanol consumption on the progressive development of T2D, particularly with respect to pancreatic β-cell mass and function in association with insulin synthesis and secretion. This review also discusses a conceptual framework for how ethanol-produced peroxynitrite contributes to pancreatic β-cell dysfunction and metabolic syndrome.
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Xie X, Gao T, Yang M, Chen P, Jin H, Yang L, Yu X. Associations of betatrophin levels with irisin in Chinese women with normal glucose tolerance. Diabetol Metab Syndr 2015; 7:26. [PMID: 25859278 PMCID: PMC4391688 DOI: 10.1186/s13098-015-0019-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Accepted: 03/05/2015] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Betatrophin may increase islet β cell proliferation in insulin resistance and irisin may improve glucose tolerance in mice. To examine the relationship between betatrophin and irisin, we investigated it in middle-aged Chinese subjects with normal glucose tolerance (NGT) and type 2 diabetes mellitus (T2DM). METHODS A total of 460 permanent residents of Fengxian District, aged 40-60 years and without T2DM, were enrolled. Anthropometric parameters, oral glucose tolerance test (OGTT) results, glycosylated haemoglobin levels, blood lipid levels, insulin sensitivity (homeostasis model assessment of insulin resistance, HOMA-IR), β cell function (homeostasis model assessment-β, HOMA-β), estimated glomerular filtration rate (eGFR) and body fat composition were determined. Matched for age, gender and body mass index (BMI, 18-28 kg/m2), newly diagnosed T2DM (n = 50, male/female = 23/27) and NGT (n = 50, male/female = 21/29) subjects were selected based on the results of an OGTT. Serum betatrophin and irisin levels were determined by enzyme linked immune sorbent assay (ELISA). RESULTS Males had higher levels of betatrophin compared with females in both the NGT and T2DM groups. Compared with NGT subjects, the level of betatrophin in the T2DM group was higher, and males in the T2DM group had higher betatrophin levels than males in the NGT group, but there was no significant difference in betatrophin levels in females between the T2DM and NGT groups. Spearman's correlation analysis revealed that serum betatrophin levels in females with NGT were positively correlated with irisin and negatively correlated with FINS (fasting insulin) levels ( p < 0.05), but no correlation was found between betatrophin and irisin levels in males with NGT or in males or females with T2DM. In females with T2DM, circulating betatrophin levels were positively correlated with weight, BMI and hip circumference (p < 0.05) but negatively correlated with FPG (fasting plasma glucose) and HOMA-IR (p < 0.05). CONCLUSIONS Gender differences in the relationship between betatrophin and irisin indicate that there might be cytokine-mediated crosstalk among the liver, adipose tissue and skeletal muscle.
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Affiliation(s)
- Xinmiao Xie
- />Department of Endocrinology and Metabolism, Fengxian Central Hospital, Shanghai, 201499 China
- />The Third Clinical Medical College of Southern Medical University, Guangzhou, 510515 China
| | - Ting Gao
- />Department of Endocrinology and Metabolism, Fengxian Central Hospital, Shanghai, 201499 China
- />Ningyang First Hospital, Ningyang, Shandong Province 271400 China
| | - Meili Yang
- />Department of Endocrinology and Metabolism, Fengxian Central Hospital, Shanghai, 201499 China
| | - Peihong Chen
- />Department of Endocrinology and Metabolism, Fengxian Central Hospital, Shanghai, 201499 China
| | - Hua Jin
- />Department of Endocrinology and Metabolism, Fengxian Central Hospital, Shanghai, 201499 China
| | - Lili Yang
- />Department of Endocrinology and Metabolism, Fengxian Central Hospital, Shanghai, 201499 China
| | - Xuemei Yu
- />Department of Endocrinology and Metabolism, Fengxian Central Hospital, Shanghai, 201499 China
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Chen K, Zhao L, He H, Wan X, Wang F, Mo Z. Silibinin protects β cells from glucotoxicity through regulation of the Insig-1/SREBP-1c pathway. Int J Mol Med 2014; 34:1073-80. [PMID: 25109869 DOI: 10.3892/ijmm.2014.1883] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Accepted: 08/04/2014] [Indexed: 11/05/2022] Open
Abstract
Exposure to high glucose may cause glucotoxicity, leading to pancreatic β cell dysfunction including cell apoptosis, impaired glucose‑stimulated insulin secretion (GSIS) and intracellular lipid accumulation. Sterol regulatory element binding protein-1c (SREBP-1c), a key nuclear transcription factor that regulates lipid metabolism, has been proven to play a role in insulin secretion. Insulin induced gene-1 (Insig-1) is an upstream regulatory factor of SREBP-1c. The overexpression of Insig-1 significantly inhibits SREBP-1c expression and thereby blocks the expression of downstream genes. It has been proven that silibinin, a natural flavanone, is involved in a variety of biological functions. In the present study, we examined whether silibinin protects high glucose-induced β cell dysfunction through the Insig-1/SREBP-1c pathway. Our data demonstrated that 30.0 µM of silibinin significantly improved cell viability (P<0.05) after rat insulinoma INS-1 cells were exposed to high glucose for 72 h. Silibinin partially attenuated GSIS following exposure to high glucose for either 24 or 72 h (both P<0.05). As shown by reverse transcription quantitative PCR, silibinin upregulated the mRNA expression of insulin secretion‑related genes [insulin receptor substrate 2 (IRS-2), pancreatic and duodenal homeobox 1 (PDX-1) and insulin], but downregulated uncoupling protein‑2 (UCP-2) expression. Silibinin inhibited intracellular lipid accumulation and free fatty acid (FFA) synthesis. Further experiments revealed that silibinin improved β cell function through the regulation of the Insig-1/SREBP-1c pathway. In conclusion, these results clearly suggest that the protection of β cells from glucotoxicity can be significantly enhanced through the regulation of the Insig-1/SREBP-1c pathway. Thus, silibinin may be a novel therapeutic agent for β cell dysfunction.
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Affiliation(s)
- Ke Chen
- Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
| | - Liling Zhao
- Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
| | - Honghui He
- Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
| | - Xinxing Wan
- Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
| | - Fang Wang
- Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
| | - Zhaohui Mo
- Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
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Abstract
Free fatty acids (FFAs) exert both positive and negative effects on beta cell survival and insulin secretory function, depending on concentration, duration, and glucose abundance. Lipid signals are mediated not only through metabolic pathways, but also through cell surface and nuclear receptors. Toxicity is modulated by positive signals arising from circulating factors such as hormones, growth factors and incretins, as well as negative signals such as inflammatory mediators and cytokines. Intracellular mechanisms of lipotoxicity include metabolic interference and cellular stress responses such as oxidative stress, endoplasmic reticulum (ER) stress, and possibly autophagy. New findings strengthen an old hypothesis that lipids may also impair compensatory beta cell proliferation. Clinical observations continue to support a role for lipid biology in the risk and progression of both type 1 (T1D) and type 2 diabetes (T2D). This review summarizes recent work in this important, rapidly evolving field.
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Affiliation(s)
- Rohit B Sharma
- Diabetes Center of Excellence, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA
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Dardano A, Penno G, Del Prato S, Miccoli R. Optimal therapy of type 2 diabetes: a controversial challenge. Aging (Albany NY) 2014; 6:187-206. [PMID: 24753144 PMCID: PMC4012936 DOI: 10.18632/aging.100646] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Accepted: 03/24/2014] [Indexed: 02/07/2023]
Abstract
Type 2 diabetes mellitus (T2DM) is one of the most common chronic disorders in older adults and the number of elderly diabetic subjects is growing worldwide. Nonetheless, the diagnosis of T2DM in elderly population is often missed or delayed until an acute metabolic emergency occurs. Accumulating evidence suggests that both aging and environmental factors contribute to the high prevalence of diabetes in the elderly. Clinical management of T2DM in elderly subjects presents unique challenges because of the multifaceted geriatric scenario. Diabetes significantly lowers the chances of "successful" aging, notably it increases functional limitations and impairs quality of life. In this regard, older diabetic patients have a high burden of comorbidities, diabetes-related complications, physical disability, cognitive impairment and malnutrition, and they are more susceptible to the complications of dysglycemia and polypharmacy. Several national and international organizations have delivered guidelines to implement optimal therapy in older diabetic patients based on individualized treatment goals. This means appreciation of the heterogeneity of the disease as generated by life expectancy, functional reserve, social support, as well as personal preference. This paper will review current treatments for achieving glycemic targets in elderly diabetic patients, and discuss the potential role of emerging treatments in this patient population.
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Affiliation(s)
- Angela Dardano
- Department of Clinical and Experimental Medicine, Section of Diabetes and Metabolic Diseases, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy
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Kurosaki Y, Tsukushi T, Munekata S, Kanoh Y, Moriya T, Nishinari M, Aoyama N, Ogawa Z. Is there a relation between triglyceride concentrations in very low density lipoprotein and the index of insulin resistance in nondiabetic subjects? J Clin Lab Anal 2014; 28:269-74. [PMID: 24578003 DOI: 10.1002/jcla.21677] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2013] [Accepted: 08/14/2013] [Indexed: 11/07/2022] Open
Abstract
BACKGROUND Serum very low density lipoprotein (VLDL) levels increase during the early stages of insulin resistance; therefore, determination of VLDL levels would be useful for evaluating the progression of metabolic syndrome and diabetes mellitus. The aim of this study was to clarify the clinical utility of triglyceride in VLDL (VLDL-TG) level, determined using a homogeneous assay kit (Shino-test Corporation, Tokyo, Japan), as an index of insulin resistance. METHODS We enrolled 74 subjects in this study (diabetic subjects, n = 42; nondiabetic subjects, n = 32). The levels of VLDL-TG, remnant-like lipoprotein particle cholesterol, preheparin lipoprotein lipase mass, and other biochemical markers were determined. RESULTS VLDL-TG levels were significantly higher in the diabetic group (1.04 ± 0.84 mmol/l vs. 0.64 ± 0.42 mmol/l, P < 0.01) than in the nondiabetic group. In the nondiabetic group, VLDL-TG was significantly correlated with the homeostasis model assessment of insulin resistance (HOMA-IR), the index for insulin resistance (r = 0.513, P = 0.003). VLDL-TG levels, but not TG levels, were higher in the highest quartile (HOMA-IR) of the nondiabetic group. CONCLUSION VLDL-TG level was a useful early marker for insulin resistance, especially in nondiabetic subjects. The homogeneous VLDL-TG assay is a simple, low-cost method for determining insulin resistance.
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Affiliation(s)
- Yoshifumi Kurosaki
- Department of Molecular Medical Biology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, Japan; Department of Clinical Chemistry, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
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Ma Y, Wang Y, Huang Q, Ren Q, Chen S, Zhang A, Zhao L, Zhen Q, Peng Y. Impaired β cell function in Chinese newly diagnosed type 2 diabetes mellitus with hyperlipidemia. J Diabetes Res 2014; 2014:493039. [PMID: 24829924 PMCID: PMC4009333 DOI: 10.1155/2014/493039] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2013] [Revised: 03/02/2014] [Accepted: 03/02/2014] [Indexed: 12/21/2022] Open
Abstract
The objective is to explore the effects of hyperlipidemia on β cell function in newly diagnosed type 2 diabetes mellitus (T2DM). 208 patients were enrolled in the study and were divided into newly diagnosed T2DM with hyperlipidemia (132 patients) and without hyperlipidemia (76 patients). Demographic data, glucose levels, insulin levels, lipid profiles, homeostasis model assessment for β cell function index (HOMA-β ), homeostasis model assessment for insulin resistance index (HOMA-IR), and quantitative insulin-sensitivity check index (QUICKI) were compared between the two groups. We found that comparing with those of normal lipid levels, the subjects of newly diagnosed T2DM with hyperlipidemia were younger, and had declined HOMA-β . However, the levels of HOMA-β were comparable regardless of different lipid profiles (combined hyperlipidemia, hypertriglyceridemia, and hypercholesterolemia). Multiple stepwise linear regression analysis showed that high fasting plasma glucose (FPG), decreased fasting insulin level (FINS), and high triglyceride (TG) were independent risk factors of β cell dysfunction in newly diagnosed T2DM. Therefore, the management of dyslipidemia, together with glucose control, may be beneficial for T2DM with hyperlipidemia.
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Affiliation(s)
- Yuhang Ma
- Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China
| | - Yufan Wang
- Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China
- *Yufan Wang:
| | - Qianfang Huang
- Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China
| | - Qian Ren
- Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China
| | - Su Chen
- Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China
| | - Aifang Zhang
- Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China
| | - Li Zhao
- Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China
| | - Qin Zhen
- Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China
| | - Yongde Peng
- Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China
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