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Kaarniranta K, Valtanen M, Keinänen-Kiukaanniemi S, Tuomilehto J, Lindström J, Uusitupa M. Long-term Cumulative Incidence of Clinically Diagnosed Retinopathy in the Finnish Diabetes Prevention Study. J Clin Endocrinol Metab 2025; 110:e615-e621. [PMID: 38661084 PMCID: PMC11834719 DOI: 10.1210/clinem/dgae287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 04/23/2024] [Accepted: 04/23/2024] [Indexed: 04/26/2024]
Abstract
CONTEXT Lifestyle intervention reduces the incidence of type 2 diabetes (T2D) in people with impaired glucose tolerance (IGT). OBJECTIVE This work aimed to find out whether participation in an earlier lifestyle intervention had an effect on the occurrence of clinically diagnosed diabetic retinopathy (DR) during a median of 22 years of follow-up time. METHODS The study included 505 individuals from the Finnish Diabetes Prevention Study (DPS) (mean age 55; range, 40-64 years at the onset of the study) with IGT who were originally randomly assigned to the intervention (weight loss, healthy diet, and physical activity) (N = 257) and usual care control groups (N = 248). The median follow-up was 22 years. Clinical retinopathy diagnoses were obtained from the Finnish national hospital Care Register for Health. Data on glycemic parameters, serum lipids, and blood pressure were available from both the intervention (median 4 years) and postintervention period (until year 7). RESULTS No significant difference was found in the cumulative incidence of clinically diagnosed DR between the original intervention (N = 23, 8.9%) and control groups (N = 19, 7.7%) during the extended follow-up (odds ratio: 1.15; 95% CI, 0.61-2.21). A higher cumulative glycated hemoglobin A1c (HbA1c) was significantly associated with a higher risk of retinopathy (hazard ratio 1.4; 1.02-1.88, 95% posterior interval, adjusted for group, age, and sex). Furthermore, the incidence of retinopathy diagnosis was numerically more common among individuals who had developed diabetes during the follow-up (33/349) compared with those who had not (9/156); however, the comparison was not statistically significant (odds ratio: 1.86, 95% CI, 0.89-4.28, adjusted for group, age, and sex). CONCLUSION A higher cumulative HbA1c was significantly associated with a higher risk of retinopathy. No evidence was found for a beneficial effect of a 4-year lifestyle intervention on the long-term occurrence of clinical DR during a median of 22-year follow-up.
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Affiliation(s)
- Kai Kaarniranta
- Institute of Medical Sciences, School of Medicine, University of Eastern Finland, 70211 Kuopio, Finland
- Department of Ophthalmology, Kuopio University Hospital, 70029, Kuopio, Finland
- Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
| | - Mikko Valtanen
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, 00271 Helsinki, Finland
| | | | - Jaakko Tuomilehto
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, 00271 Helsinki, Finland
- Department of Public Health, University of Helsinki, 00014 Helsinki, Finland
- Saudi Diabetes Research Group, King Abdulaziz University, 21589 Jeddah, Saudi Arabia
| | - Jaana Lindström
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, 00271 Helsinki, Finland
| | - Matti Uusitupa
- School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland
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Li YQ, Zhang LY, Zhao YC, Xu F, Hu ZY, Wu QH, Li WH, Li YN. Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion. World J Diabetes 2023; 14:1643-1658. [DOI: 10.4239/wjd.v14.i11.1643] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 07/11/2023] [Accepted: 09/06/2023] [Indexed: 11/14/2023] Open
Abstract
BACKGROUND Impaired glucose tolerance (IGT) is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes. When IGT occurs, insulin sensitivity decreases, causing a reduction in insulin secretion and an increase in glucagon secretion. Recently, vascular endothelial growth factor B (VEGFB) has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity. Therefore, we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion, thus contributing to the prevention and cure of prediabetes.
AIM To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT.
METHODS We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression. Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay, and the protein expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) was determined using western blot. Further, mRNA expression of forkhead box protein O1, phosphoenolpyruvate carboxykinase, and glucose-6 phosphatase was detected via quantitative polymerase chain reaction, and the correlation between the expression of proteins was analyzed via bioinformatics.
RESULTS In mice with IGT and VEGFB knockout, glucagon secretion increased, and the protein expression of PI3K/AKT decreased dramatically. Further, in mice with VEGFB overexpression, glucagon levels declined, with the activation of the PI3K/AKT signaling pathway.
CONCLUSION VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.
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Affiliation(s)
- Yu-Qi Li
- Department of Pathophysiology, School of Basic Medicine, Binzhou Medical University, Yantai 264000, Shandong Province, China
| | - Lu-Yang Zhang
- Department of Rheumatology and Immunology, Yantaishan Hospital, Yantai 264000, Shandong Province, China
| | - Yu-Chi Zhao
- Department of Surgery, Yantaishan Hospital, Yantai 264000, Shandong Province, China
| | - Fang Xu
- Department of Pathophysiology, School of Basic Medicine, Binzhou Medical University, Yantai 264000, Shandong Province, China
| | - Zhi-Yong Hu
- School of Public Health and Management, Binzhou Medical University, Yantai 264000, Shandong Province, China
| | - Qi-Hao Wu
- The First School of Clinical Medicine, Binzhou Medical University, Yantai 264000, Shandong Province, China
| | - Wen-Hao Li
- Department of Pathophysiology, School of Basic Medicine, Binzhou Medical University, Yantai 264000, Shandong Province, China
| | - Ya-Nuo Li
- Department of Pathophysiology, School of Basic Medicine, Binzhou Medical University, Yantai 264000, Shandong Province, China
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Collins KA, Ross LM, Slentz CA, Huffman KM, Kraus WE. Differential Effects of Amount, Intensity, and Mode of Exercise Training on Insulin Sensitivity and Glucose Homeostasis: A Narrative Review. SPORTS MEDICINE - OPEN 2022; 8:90. [PMID: 35834023 PMCID: PMC9283590 DOI: 10.1186/s40798-022-00480-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 06/18/2022] [Indexed: 11/29/2022]
Abstract
As type 2 diabetes remains a leading cause of morbidity and mortality, identifying the most appropriate preventive treatment early in the development of disease is an important public health matter. In general, lifestyle interventions incorporating exercise and weight loss via caloric restriction improve cardiometabolic risk by impacting several key markers of insulin sensitivity and glucose homeostasis. However, variations in the effects of specific types of exercise interventions on these markers have led to conflicting results surrounding the optimal amount, intensity, and mode of exercise for optimal effects. Moreover, the addition of weight loss via caloric restriction to exercise interventions appears to differentially impact changes in body composition, metabolism, and insulin sensitivity compared to exercise alone. Determining the optimal amount, intensity, and mode of exercise having the most beneficial impact on glycemic status is both: (1) clinically important to provide guidelines for appropriate exercise prescription; and (2) physiologically important to understand the pathways by which exercise-with and without weight loss-impacts glycemic status to enhance precision lifestyle medicine. Thus, the purposes of this narrative review are to: (1) summarize findings from the three Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) randomized trials regarding the differential effects of exercise amount, intensity, and mode on insulin action and glucose homeostasis markers; and (2) compare the STRRIDE findings to other published dose-response exercise trials in order to piece together the various physiologic pathways by which specific exercise interventions-with or without weight loss-impact glycemic status.
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Affiliation(s)
- Katherine A Collins
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
| | - Leanna M Ross
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
| | - Cris A Slentz
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
| | - Kim M Huffman
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
| | - William E Kraus
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
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Chen M, Moran LJ, Harrison CL, Ukke GG, Sood S, Bennett CJ, Bahri Khomami M, Absetz P, Teede H, Lim S. Ethnic differences in response to lifestyle intervention for the prevention of type 2 diabetes in adults: A systematic review and meta-analysis. Obes Rev 2022; 23:e13340. [PMID: 34528393 DOI: 10.1111/obr.13340] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 08/05/2021] [Accepted: 08/05/2021] [Indexed: 12/30/2022]
Abstract
The risk of type 2 diabetes mellitus (T2DM) varies by ethnicity, but ethnic differences in response to diabetes prevention interventions remain unclear. This systematic review and meta-analysis assessed ethnic differences in the effects of lifestyle interventions on T2DM incidence, glycemic outcomes (fasting glucose, 2-h glucose, HbA1c ), anthropometric measures (weight, BMI, waist circumference), and lifestyle behaviors (physical activity, energy intake, energy from fat, fiber intake). MEDLINE, EMBASE, and other databases were searched (to June 15, 2020) for randomized and non-randomized controlled trials on lifestyle interventions (diet and/or physical activity) in adults at risk of T2DM. Ethnicity was categorized into European, South Asian, East and Southeast Asian, Middle Eastern, Latin American, and African groups. Forty-four studies were included in meta-analyses. Overall, lifestyle interventions resulted in significant improvement in T2DM incidence, glycemic outcomes, anthropometric measures, physical activity, and energy intake (all P < 0.01). Significant subgroup differences by ethnicity were found for 2-h glucose, weight, BMI, and waist circumference (all P < 0.05) but not for T2DM incidence, fasting glucose, HbA1c , and physical activity (all P > 0.05). Few studies in non-European groups reported dietary intake. Lifestyle interventions in different ethnic groups may have similar effects in reducing incidence of T2DM although this needs to be confirmed in further studies.
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Affiliation(s)
- Mingling Chen
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia
| | - Lisa J Moran
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia
| | - Cheryce L Harrison
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia
| | - Gebresilasea Gendisha Ukke
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia
| | - Surbhi Sood
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia
| | - Christie J Bennett
- Department of Nutrition, Dietetics and Food, School of Clinical Sciences, Monash University, Notting Hill, Victoria, Australia
| | - Mahnaz Bahri Khomami
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia
| | - Pilvikki Absetz
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Helena Teede
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia
| | - Siew Lim
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia
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de Mello VD, Selander T, Lindström J, Tuomilehto J, Uusitupa M, Kaarniranta K. Serum Levels of Plasmalogens and Fatty Acid Metabolites Associate with Retinal Microangiopathy in Participants from the Finnish Diabetes Prevention Study. Nutrients 2021; 13:nu13124452. [PMID: 34960007 PMCID: PMC8703764 DOI: 10.3390/nu13124452] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/08/2021] [Accepted: 12/09/2021] [Indexed: 02/07/2023] Open
Abstract
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes, and retinal microaneurysms (MA) are one of the first detected abnormalities associated with DR. We recently showed elevated serum triglyceride levels to be associated with the development of MA in the Finnish Diabetes Prevention Study (DPS). The purpose of this metabolomics study was to assess whether serum fatty acid (FA) composition, plasmalogens, and low-grade inflammation may enhance or decrease the risk of MA. Originally, the DPS included 522 individuals (mean 55 years old, range 40-64 years) with impaired glucose tolerance who were randomized into an intervention (n = 265) or control group (n = 257). The intervention lasted for a median of four years (active period), after which annual follow-up visits were conducted. At least five years after stopping the intervention phase of DPS, participants classified as MA negative (n = 115) or MA positive (n = 51) were included in the current study. All these participants were free of diabetes at baseline (WHO 1985) and had high-sensitive C-reactive protein (hs-CRP), serum FA composition, and selected lipid metabolites measured during the active study period. Among the markers associated with MA, the serum plasmalogen dm16:0 (p = 0.006), the saturated odd-chain FA 15.0 (pentadecanoic acid; p = 0.015), and omega-3 very long-chain FAs (p < 0.05) were associated with a decreased occurrence of MA. These associations were independent of study group and other risk factors. The association of high serum triglycerides with the MA occurrence was attenuated when these MA-associated serum lipid markers were considered. Our findings suggest that, in addition to n-3 FAs, odd-chain FA 15:0 and plasmalogen dm16:0 may contribute to a lower risk of MA in individuals with impaired glucose tolerance. These putative novel lipid biomarkers have an association with MA independently of triglyceride levels.
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Affiliation(s)
- Vanessa Derenji de Mello
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, FI-70211 Kuopio, Finland;
- Correspondence:
| | - Tuomas Selander
- Science Service Center, Kuopio University Hospital, FI-70029 Kuopio, Finland;
| | - Jaana Lindström
- Public Health Prevention Unit, Finnish Institute for Health and Welfare, FI-00271 Helsinki, Finland; (J.L.); (J.T.)
| | - Jaakko Tuomilehto
- Public Health Prevention Unit, Finnish Institute for Health and Welfare, FI-00271 Helsinki, Finland; (J.L.); (J.T.)
- Department of Public Health, University of Helsinki, FI-00014 Helsinki, Finland
- Diabetes Research Group, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Matti Uusitupa
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, FI-70211 Kuopio, Finland;
| | - Kai Kaarniranta
- Department of Ophthalmology, Kuopio University Hospital, FI-70029 Kuopio, Finland;
- Institute of Clinical Medicine, Faculty of Health Sciences, University of Eastern Finland, FI-70211 Kuopio, Finland
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Fritsche A, Wagner R, Heni M, Kantartzis K, Machann J, Schick F, Lehmann R, Peter A, Dannecker C, Fritsche L, Valenta V, Schick R, Nawroth PP, Kopf S, Pfeiffer AFH, Kabisch S, Dambeck U, Stumvoll M, Blüher M, Birkenfeld AL, Schwarz P, Hauner H, Clavel J, Seißler J, Lechner A, Müssig K, Weber K, Laxy M, Bornstein S, Schürmann A, Roden M, de Angelis MH, Stefan N, Häring HU. Different Effects of Lifestyle Intervention in High- and Low-Risk Prediabetes: Results of the Randomized Controlled Prediabetes Lifestyle Intervention Study (PLIS). Diabetes 2021; 70:2785-2795. [PMID: 34531293 DOI: 10.2337/db21-0526] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Accepted: 09/08/2021] [Indexed: 11/13/2022]
Abstract
Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested whether individuals with prediabetes with low risk (LR) benefit from conventional LI and individuals with high risk (HR) benefit from an intensification of LI in a multicenter randomized controlled intervention over 12 months with 2 years' follow-up. A total of 1,105 individuals with prediabetes based on American Diabetes Association glucose criteria were stratified into an HR or LR phenotype based on previously described thresholds of insulin secretion, insulin sensitivity, and liver fat content. LR individuals were randomly assigned to conventional LI according to the Diabetes Prevention Program (DPP) protocol or control (1:1) and HR individuals to conventional or intensified LI with doubling of required exercise (1:1). A total of 908 (82%) participants completed the study. In HR individuals, the difference between conventional and intensified LI in postchallenge glucose change was -0.29 mmol/L [95% CI -0.54; -0.04], P = 0.025. Liver fat (-1.34 percentage points [95% CI -2.17; -0.50], P = 0.002) and cardiovascular risk (-1.82 percentage points [95% CI -3.13; -0.50], P = 0.007) underwent larger reductions with intensified than with conventional LI. During a follow-up of 3 years, intensified compared with conventional LI had a higher probability of normalizing glucose tolerance (P = 0.008). In conclusion, it is possible in HR individuals with prediabetes to improve glycemic and cardiometabolic outcomes by intensification of LI. Individualized, risk phenotype-based LI may be beneficial for the prevention of diabetes.
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Affiliation(s)
- Andreas Fritsche
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, Eberhard-Karls University Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Robert Wagner
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, Eberhard-Karls University Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Martin Heni
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, Eberhard-Karls University Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Kostantinos Kantartzis
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, Eberhard-Karls University Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Jürgen Machann
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- Section on Experimental Radiology, Department of Radiology, University of Tübingen, Tübingen, Germany
| | - Fritz Schick
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Section on Experimental Radiology, Department of Radiology, University of Tübingen, Tübingen, Germany
| | - Rainer Lehmann
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Andreas Peter
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Corinna Dannecker
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Louise Fritsche
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Vera Valenta
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Renate Schick
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Peter Paul Nawroth
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany
- Institute for Diabetes and Cancer, IDC Helmholtz Center, Munich, Germany
- Joint Heidelberg-IDC Translational Diabetes Program, Neuherberg, Germany
| | - Stefan Kopf
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany
| | - Andreas F H Pfeiffer
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Stefan Kabisch
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Ulrike Dambeck
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Michael Stumvoll
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Medicine, Endocrinology and Nephrology, Universität Leipzig, Leipzig, Germany
| | - Matthias Blüher
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Medicine, Endocrinology and Nephrology, Universität Leipzig, Leipzig, Germany
| | - Andreas L Birkenfeld
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany
| | - Peter Schwarz
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany
| | - Hans Hauner
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute of Nutritional Medicine, School of Medicine, Technical University of Munich, Munich, Germany
| | - Julia Clavel
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute of Nutritional Medicine, School of Medicine, Technical University of Munich, Munich, Germany
| | - Jochen Seißler
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Diabetes Research Group, Medical Department 4, Ludwig-Maximilians University Munich, Munich, Germany
| | - Andreas Lechner
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Diabetes Research Group, Medical Department 4, Ludwig-Maximilians University Munich, Munich, Germany
| | - Karsten Müssig
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Katharina Weber
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Michael Laxy
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute of Health Economics and Health Care Management, Neuherberg, Germany
| | - Stefan Bornstein
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany
| | - Annette Schürmann
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Michael Roden
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Martin Hrabe de Angelis
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute of Experimental Genetics, IEG Helmholtz Center Munich, Neuherberg, Germany
- Chair of Experimental Genetics, School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany
| | - Norbert Stefan
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, Eberhard-Karls University Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Hans-Ulrich Häring
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, Eberhard-Karls University Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
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7
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Haverinen A, Kangasniemi M, Luiro K, Piltonen T, Heikinheimo O, Tapanainen JS. Ethinyl estradiol vs estradiol valerate in combined oral contraceptives - Effect on glucose tolerance: A randomized, controlled clinical trial. Contraception 2020; 103:53-59. [PMID: 33098852 DOI: 10.1016/j.contraception.2020.10.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 10/14/2020] [Accepted: 10/14/2020] [Indexed: 10/23/2022]
Abstract
OBJECTIVE To compare the effects of two formulations of combined oral contraceptives (COCs), estradiol valerate (EV) and ethinyl estradiol (EE) combined with dienogest (DNG), and DNG-only, on glucose tolerance. STUDY DESIGN We performed a randomized, controlled 9-week clinical trial. Inclusion criteria were: age 18-35 years, regular menstrual cycle (28 ± 7 days), no polycystic ovaries, non-smoking, no contraindications for COC use and a 2-month wash-out from hormonal contraceptive use. The women were randomized to EV + DNG (n = 20), EE + DNG (n = 20), and DNG-only (n = 19), and evaluated at baseline, at 4-5 weeks and 8-9 weeks of treatment. Study medications were used continuously for 63 days. Primary outcome measure was change in the whole-body insulin sensitivity index (Matsuda index) derived from the oral glucose tolerance test (OGTT) over the treatment period. Secondary outcome measures were area under curves (AUC) of glucose and insulin, homeostatic model assessment - insulin resistance (HOMA-IR) and Insulin Sensitivity Index (ISI). RESULTS Fifty-nine women enrolled, and 56 women completed the study. The Matsuda index changed from baseline as follows (mean percentage change, mean change [95%CI]): DNG-only -12%, -1.45 [95%CI -3.22-0.325] P = 0.10; EV + DNG + 2.7%, -0.10 [-1.34 to 1.14] P = 0.86; EE + DNG -5.5%, -1.02 [-2.51 to 0.46] P = 0.16, comparing the groups P = 0.27. There were no clinically significant differences in glucose tolerance between the COC groups, but the DNG-only group showed an improvement in the 2-h glucose levels (5.5 [95%CI 5.0-6.0] to 4.7 mmol/l [4.2-5.2], P = 0.001). CONCLUSION We found no clinically significant differences between EV and EE combined with DNG and DNG-only on glucose tolerance in healthy, young, normal-weight women, indicating that these preparations appear close to neutral regarding glucose metabolism when used continuously for nine weeks. IMPLICATIONS Combinations of both ethinyl estradiol and natural estradiol (estradiol valerate) with dienogest (DNG), as well as DNG-only, seem metabolically safe in young and healthy women in short-term continuous use.
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Affiliation(s)
- Annina Haverinen
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 2, PO 140, 00029 Helsinki, Finland
| | - Marika Kangasniemi
- Department of Obstetrics and Gynecology, University of Oulu, Oulu University Hospital and Medical Research Centre PEDEGO Research Unit, Kajaanintie 50, PO 5000, 90014 Oulu, Finland
| | - Kaisu Luiro
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 2, PO 140, 00029 Helsinki, Finland
| | - Terhi Piltonen
- Department of Obstetrics and Gynecology, University of Oulu, Oulu University Hospital and Medical Research Centre PEDEGO Research Unit, Kajaanintie 50, PO 5000, 90014 Oulu, Finland
| | - Oskari Heikinheimo
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 2, PO 140, 00029 Helsinki, Finland
| | - Juha S Tapanainen
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 2, PO 140, 00029 Helsinki, Finland; Department of Obstetrics and Gynecology, University of Oulu, Oulu University Hospital and Medical Research Centre PEDEGO Research Unit, Kajaanintie 50, PO 5000, 90014 Oulu, Finland.
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8
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Pre-analytical Errors in Glucose Estimation Results in Query on Diabetic Management. Indian J Clin Biochem 2020; 35:32-42. [DOI: 10.1007/s12291-018-0782-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Accepted: 07/05/2018] [Indexed: 10/28/2022]
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Uusitupa M, Khan TA, Viguiliouk E, Kahleova H, Rivellese AA, Hermansen K, Pfeiffer A, Thanopoulou A, Salas-Salvadó J, Schwab U, Sievenpiper JL. Prevention of Type 2 Diabetes by Lifestyle Changes: A Systematic Review and Meta-Analysis. Nutrients 2019; 11:2611. [PMID: 31683759 PMCID: PMC6893436 DOI: 10.3390/nu11112611] [Citation(s) in RCA: 223] [Impact Index Per Article: 37.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 10/10/2019] [Accepted: 10/18/2019] [Indexed: 12/12/2022] Open
Abstract
Prevention of type 2 diabetes (T2D) is a great challenge worldwide. The aim of this evidence synthesis was to summarize the available evidence in order to update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy. We conducted a systematic review and, where appropriate, meta-analyses of randomized controlled trials (RCTs) carried out in people with impaired glucose tolerance (IGT) (six studies) or dysmetabolism (one study) to answer the following questions: What is the evidence that T2D is preventable by lifestyle changes? What is the optimal diet (with a particular focus on diet quality) for prevention, and does the prevention of T2D result in a lower risk of late complications of T2D? The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to assess the certainty of the trial evidence. Altogether seven RCTs (N = 4090) fulfilled the eligibility criteria and were included in the meta-analysis. The diagnosis of incident diabetes was based on an oral glucose tolerance test (OGTT). The overall risk reduction of T2D by the lifestyle interventions was 0.53 (95% CI 0.41; 0.67). Most of the trials aimed to reduce weight, increase physical activity, and apply a diet relatively low in saturated fat and high in fiber. The PREDIMED trial that did not meet eligibility criteria for inclusion in the meta-analysis was used in the final assessment of diet quality. We conclude that T2D is preventable by changing lifestyle and the risk reduction is sustained for many years after the active intervention (high certainty of evidence). Healthy dietary changes based on the current recommendations and the Mediterranean dietary pattern can be recommended for the long-term prevention of diabetes. There is limited or insufficient data to show that prevention of T2D by lifestyle changes results in a lower risk of cardiovascular and microvascular complications.
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Affiliation(s)
- Matti Uusitupa
- Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
| | - Tauseef A Khan
- Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's hospital, Toronto, ON M5B 1W8, Canada.
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A1, Canada.
| | - Effie Viguiliouk
- Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's hospital, Toronto, ON M5B 1W8, Canada.
| | - Hana Kahleova
- Physicians Committee for Responsible Medicine, Washington, DC 20016, USA.
- Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic.
| | - Angela A Rivellese
- Department of Clinical Medicine and Surgery, Federico II University, 80138 Naples, Italy.
| | - Kjeld Hermansen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark.
| | - Andreas Pfeiffer
- German Institute of Human Nutrition Potsdam-Rehbrücke, Clinical Nutrition-DZD, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany.
- Department of Endocrinology, Charité University Medicine, Diabetes and Nutrition, Campus Benjamin Franklin, Hindenburgdamm 30, D-12203 Berlin, Germany.
- German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
| | - Anastasia Thanopoulou
- Diabetes Center, 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, 157 72 Athens, Greece.
| | - Jordi Salas-Salvadó
- Human Nutrition Unit, University Hospital of Sant Joan de Reus, Department of Biochemistry and Biotechnology, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, 43201 Reus, Spain.
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, Spain.
| | - Ursula Schwab
- Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
- Department of Medicine, Endocrinology and Clinical Nutrition, Kuopio University Hospital, 70210 Kuopio, Finland.
| | - John L Sievenpiper
- Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's hospital, Toronto, ON M5B 1W8, Canada.
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A1, Canada.
- Division of Endocrinology and Metabolism, Department of Medicine, St. Michael's Hospital, Toronto, M5B 1W8 ON, Canada.
- Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, M5B 1T8 ON, Canada.
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10
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Life Style Intervention Improves Retinopathy Status-The Finnish Diabetes Prevention Study. Nutrients 2019; 11:nu11071691. [PMID: 31340493 PMCID: PMC6683279 DOI: 10.3390/nu11071691] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 07/16/2019] [Accepted: 07/19/2019] [Indexed: 11/17/2022] Open
Abstract
The aim of the study was to find out whether participation in earlier intervention had an effect on the occurrence of retinopathy in study participants. We also examined risk factors (age, sex, weight, fasting and 2 h glucose, fasting insulin, blood pressure, serum lipids) for early retinal changes. The study included 522 individuals (mean 55 years old, range 40-64 years) with impaired glucose tolerance who were randomized into intervention (weight loss, healthy diet, and physical activity, N = 265) and control groups (N = 257). Intervention lasted for median of four years in 1993-2000, after which annual follow-up visits at study clinics were conducted. In the years 2002-2006 (at least five years after stopping intervention), fundus photography was offered for all study participants in four of five study clinics. Photographs were assessed by two experienced ophthalmologists (A.A. and K.K.), masked for the group assignment. After exclusion of poor quality photographs, the data of 211 individuals (N = 113 for intervention and N = 98 for control group) were included in the present study. The occurrence of microaneurysms was significantly higher in the control (37/98, 38%) than in the intervention group (27/113, 24%; p = 0.029). In the model, including age, sex, diabetes diagnosis before the retinal assessment, body mass index (BMI), and treatment group, the odds ratio for microaneurysms was markedly lower in intervention group (OR 0.52; 0.28-0.97, p = 0.039). The only risk factor that predicted the occurrence of microaneurysms was serum triglycerides at baseline (mean ± SD 1.9 ± 0.9 vs. 1.6 ± 0.7, mmol/L, with and without microaneurysms, respectively, p = 0.003). Triglycerides associated with decreased microaneurysms in regression analysis for age, sex, fasting glucose, and intervention group (OR 1.92, p = 0.018). Lifestyle intervention in overweight and obese individuals with impaired glucose tolerance showed decreased occurrence of retinal microaneurysms. Elevated serum triglycerides were associated to the development of early diabetic microangiopathy.
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Pihlajamäki J, Männikkö R, Tilles-Tirkkonen T, Karhunen L, Kolehmainen M, Schwab U, Lintu N, Paananen J, Järvenpää R, Harjumaa M, Martikainen J, Kohl J, Poutanen K, Ermes M, Absetz P, Lindström J, Lakka TA. Digitally supported program for type 2 diabetes risk identification and risk reduction in real-world setting: protocol for the StopDia model and randomized controlled trial. BMC Public Health 2019; 19:255. [PMID: 30823909 PMCID: PMC6397451 DOI: 10.1186/s12889-019-6574-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Accepted: 02/21/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The StopDia study is based on the convincing scientific evidence that type 2 diabetes (T2D) and its comorbidities can be prevented by a healthy lifestyle. The need for additional research is based on the fact that the attempts to translate scientific evidence into actions in the real-world health care have not led to permanent and cost-effective models to prevent T2D. The specific aims of the StopDia study following the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework are to 1) improve the Reach of individuals at increased risk, 2) evaluate the Effectiveness and cost-effectiveness of the digital lifestyle intervention and the digital and face-to-face group lifestyle intervention in comparison to routine care in a randomized controlled trial (RCT), and 3) evaluate the Adoption and Implementation of the StopDia model by the participants and the health care organizations at society level. Finally, we will address the Maintenance of the lifestyle changes at participant level and that of the program at organisatory level after the RCT. METHODS The StopDia study is carried out in the primary health care system as part of the routine actions of three provinces in Finland, including Northern Savo, Southern Carelia, and Päijät-Häme. We estimate that one fifth of adults aged 18-70 years living in these areas are at increased risk of T2D. We recruit the participants using the StopDia Digital Screening Tool, including questions from the Finnish Diabetes Risk Score (FINDRISC). About 3000 individuals at increased risk of T2D (FINDRISC ≥12 or a history of gestational diabetes, impaired fasting glucose, or impaired glucose tolerance) participate in the one-year randomized controlled trial. We monitor lifestyle factors using the StopDia Digital Questionnaire and metabolism using laboratory tests performed as part of routine actions in the health care system. DISCUSSION Sustainable and scalable models are needed to reach and identify individuals at increased risk of T2D and to deliver personalized and effective lifestyle interventions. With the StopDia study we aim to answer these challenges in a scientific project that is fully digitally integrated into the routine health care. TRIAL REGISTRATION ClinicalTials.gov . Identifier: NCT03156478 . Date of registration 17.5.2017.
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Affiliation(s)
- Jussi Pihlajamäki
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, Finland
- Clinical Nutrition and Obesity Center, Kuopio University Hospital, Kuopio, Finland
| | - Reija Männikkö
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, Finland
- Department of Medicine, Endocrinology and Clinical Nutrition, Kuopio University Hospital, Kuopio, Finland
| | - Tanja Tilles-Tirkkonen
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, Finland
| | - Leila Karhunen
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, Finland
| | - Marjukka Kolehmainen
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, Finland
| | - Ursula Schwab
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, Finland
- Department of Medicine, Endocrinology and Clinical Nutrition, Kuopio University Hospital, Kuopio, Finland
| | - Niina Lintu
- Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
| | - Jussi Paananen
- Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
| | - Riia Järvenpää
- Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland
| | - Marja Harjumaa
- VTT Technical Research Centre of Finland Ltd., Espoo, Finland
| | | | - Johanna Kohl
- VTT Technical Research Centre of Finland Ltd., Espoo, Finland
| | - Kaisa Poutanen
- VTT Technical Research Centre of Finland Ltd., Espoo, Finland
| | - Miikka Ermes
- VTT Technical Research Centre of Finland Ltd., Espoo, Finland
| | - Pilvikki Absetz
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, Finland
- Collaborative Care Systems Finland, Helsinki, Finland
| | - Jaana Lindström
- Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland
| | - Timo A. Lakka
- Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
- Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland
- Kuopio Research Institute of Exercise Medicine, Kuopio, Finland
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12
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Guess ND. Dietary Interventions for the Prevention of Type 2 Diabetes in High-Risk Groups: Current State of Evidence and Future Research Needs. Nutrients 2018; 10:E1245. [PMID: 30200572 PMCID: PMC6163866 DOI: 10.3390/nu10091245] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 08/28/2018] [Accepted: 08/30/2018] [Indexed: 12/13/2022] Open
Abstract
A series of large-scale randomised controlled trials have demonstrated the effectiveness of lifestyle change in preventing type 2 diabetes in people with impaired glucose tolerance. Participants in these trials consumed a low-fat diet, lost a moderate amount of weight and/or increased their physical activity. Weight loss appears to be the primary driver of type 2 diabetes risk reduction, with individual dietary components playing a minor role. The effect of weight loss via other dietary approaches, such as low-carbohydrate diets, a Mediterranean dietary pattern, intermittent fasting or very-low-energy diets, on the incidence of type 2 diabetes has not been tested. These diets-as described here-could be equally, if not more effective in preventing type 2 diabetes than the tested low-fat diet, and if so, would increase choice for patients. There is also a need to understand the effect of foods and diets on beta-cell function, as the available evidence suggests moderate weight loss, as achieved in the diabetes prevention trials, improves insulin sensitivity but not beta-cell function. Finally, prediabetes is an umbrella term for different prediabetic states, each with distinct underlying pathophysiology. The limited data available question whether moderate weight loss is effective at preventing type 2 diabetes in each of the prediabetes subtypes.
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Affiliation(s)
- Nicola D Guess
- Department of Nutritional Sciences, King's College London, 150 Stamford Street, Room 4.13, London SE1 9NH, UK.
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13
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Prevention of type 2 diabetes-success story that is waiting for next steps. Eur J Clin Nutr 2018; 72:1260-1266. [PMID: 30185842 DOI: 10.1038/s41430-018-0223-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Accepted: 05/17/2018] [Indexed: 12/27/2022]
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14
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Associations of serum indolepropionic acid, a gut microbiota metabolite, with type 2 diabetes and low-grade inflammation in high-risk individuals. Nutr Diabetes 2018; 8:35. [PMID: 29795366 PMCID: PMC5968030 DOI: 10.1038/s41387-018-0046-9] [Citation(s) in RCA: 162] [Impact Index Per Article: 23.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Revised: 04/19/2018] [Accepted: 05/01/2018] [Indexed: 12/14/2022] Open
Abstract
We recently reported using non-targeted metabolic profiling that serum indolepropionic acid (IPA), a microbial metabolite of tryptophan, was associated with a lower likelihood of developing type 2 diabetes (T2D). In the present study, we established a targeted quantitative method using liquid chromatography with mass spectrometric detection (HPLC-QQQ-MS/MS) and measured the serum concentrations of IPA in all the participants from the Finnish Diabetes Prevention Study (DPS), who had fasting serum samples available from the 1-year study follow-up (n = 209 lifestyle intervention and n = 206 control group). Higher IPA at 1-year study was inversely associated with the incidence of T2D (OR [CI]: 0.86 [0.73–0.99], P = 0.04) and tended to be directly associated with insulin secretion (β = 0.10, P = 0.06) during the mean 7-year follow-up. Moreover, IPA correlated positively with dietary fiber intake (g/day: r = 0.24, P = 1 × 10−6) and negatively with hsCRP concentrations at both sampling (r = − 0.22, P = 0.0001) and study follow-up (β = − 0.19, P = 0.001). Thus, we suggest that the putative effect of IPA on lowering T2D risk might be mediated by the interplay between dietary fiber intake and inflammation or by direct effect of IPA on β-cell function.
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15
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A Plant-Based Dietary Intervention Improves Beta-Cell Function and Insulin Resistance in Overweight Adults: A 16-Week Randomized Clinical Trial. Nutrients 2018; 10:nu10020189. [PMID: 29425120 PMCID: PMC5852765 DOI: 10.3390/nu10020189] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Revised: 01/30/2018] [Accepted: 02/05/2018] [Indexed: 12/17/2022] Open
Abstract
The aim of this study was to test the effect of a plant-based dietary intervention on beta-cell function in overweight adults with no history of diabetes. Participants (n = 75) were randomized to follow a low-fat plant-based diet (n = 38) or to make no diet changes (n = 37) for 16 weeks. At baseline and 16 weeks, beta-cell function was quantified with a mathematical model. Using a standard meal test, insulin secretory rate was calculated by C-peptide deconvolution. The Homeostasis Model Assessment (HOMA-IR) index was used to assess insulin resistance while fasting. A marked increase in meal-stimulated insulin secretion was observed in the intervention group compared with controls (interaction between group and time, Gxt, p < 0.001). HOMA-IR index fell significantly (p < 0.001) in the intervention group (treatment effect −1.0 (95% CI, −1.2 to −0.8); Gxt, p = 0.004). Changes in HOMA-IR correlated positively with changes in body mass index (BMI) and visceral fat volume (r = 0.34; p = 0.009 and r = 0.42; p = 0.001, respectively). The latter remained significant after adjustment for changes in BMI (r = 0.41; p = 0.002). Changes in glucose-induced insulin secretion correlated negatively with BMI changes (r = −0.25; p = 0.04), but not with changes in visceral fat. Beta-cell function and insulin sensitivity were significantly improved through a low-fat plant-based diet in overweight adults.
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Silvestre MP, Goode JP, Vlaskovsky P, McMahon C, Tay A, Poppitt SD. The role of glucagon in weight loss-mediated metabolic improvement: a systematic review and meta-analysis. Obes Rev 2018; 19:233-253. [PMID: 29144030 DOI: 10.1111/obr.12631] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2017] [Revised: 08/30/2017] [Accepted: 09/19/2017] [Indexed: 02/06/2023]
Abstract
Aims This meta-analysis aimed to investigate the role of glucagon suppression in regulating glucose homeostasis following diet or bariatric surgery. Methods A comprehensive search of intervention and observational studies was conducted in Medline, Scopus, Web of Science, PubMed and Embase. Random effects model meta-analysis was performed. Primary outcomes were (i) body weight change, (ii) fasting glucagon, (iii) fasting glucose and (iv) fasting insulin concentrations. Results Twenty articles reporting data from 29 interventions were eligible for analysis. Bariatric surgery caused greater weight loss than diet (bariatric -29.7 kg [CI:-36.8, -22.6]; diet -5.8 kg [CI: -8.4, -3.3]; P < 0.00001), an effect that remained significant after adjusting for study duration (P < 0.05). Mean fasting glucagon decreased in parallel with weight loss (-11.8 ng/L [CI: -15.9, -7.8]; P < 0.00001) with no difference between bariatric and diet intervention. Both fasting glucose, and insulin decreased following weight loss (both P < 0.00001; glucose -1.7 mmol/L [CI: -2.0, -1.3]; insulin -50.6 pmol/L [CI: -66.5, -34.7] with greater decrease in fasting insulin between bariatric versus diet (P = 0.01). Conclusions Synergistic suppression of fasting glucagon and insulin resistance may act together to restore normoglycaemia following weight loss. Whether suppression of plasma glucagon may contribute to increased hunger after weight loss and gradual weight regain is not yet known.
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Affiliation(s)
- M P Silvestre
- Human Nutrition Unit, University of Auckland, Auckland, New Zealand.,School of Biological Sciences, University of Auckland, Auckland, New Zealand
| | - J P Goode
- Human Nutrition Unit, University of Auckland, Auckland, New Zealand
| | - P Vlaskovsky
- Department of Statistics, University of Auckland, Auckland, New Zealand
| | - C McMahon
- Human Nutrition Unit, University of Auckland, Auckland, New Zealand
| | - A Tay
- Human Nutrition Unit, University of Auckland, Auckland, New Zealand
| | - S D Poppitt
- Human Nutrition Unit, University of Auckland, Auckland, New Zealand.,School of Biological Sciences, University of Auckland, Auckland, New Zealand.,Department of Medicine, University of Auckland, Auckland, New Zealand
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Zhang WQ, Tian Y, Chen XM, Wang LF, Chen CC, Qiu CM. Liraglutide ameliorates beta-cell function, alleviates oxidative stress and inhibits low grade inflammation in young patients with new-onset type 2 diabetes. Diabetol Metab Syndr 2018; 10:91. [PMID: 30564288 PMCID: PMC6296090 DOI: 10.1186/s13098-018-0392-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Accepted: 12/11/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The prevalence of type 2 diabetes in youth is escalating rapidly. We aimed to evaluate the effects of liraglutide on beta-cell function, metabolic productions of oxidative stress, low grade inflammation compared with metformin in young patients with recent onset type 2 diabetes mellitus. METHODS Sixty patients were randomly assigned to receive 8-week liraglutide or metformin treatment. Beta-cell function was assessed by modified beta cell function index (MBCI), early phase of insulin secretion index (ΔI30/ΔG30), proinsuin to insulin ratio (P/I) and the insulin area under the curve (AUCins). The expression of 8-OH-dG and 8-iso-PGF2α and hs-C-reactive protein (hs-CRP) were measured as indications of oxidative stress and low grade inflammation. RESULTS After 8 weeks liraglutide treatment, MBCI, ΔI30/ΔG30, AUCins significantly increased, 8-OH-dG, 8-iso-PGF2α, P/I and hs-CRP remarkably reduced. The differences before and after 8-week liraglutide treatment in ΔMBCI (11.1 [2.81, 43.08] vs 0.00 [- 8.16, 10.47], P = 0.017), ΔLNΔI30/ΔG30 (0.44 [0.04, 0.85] vs - 0.09 [- 0.33, 0.36], P = 0.049), ΔAUCins (117 [- 8, 376] vs - 21 [- 314, 109] mIU/L, P = 0.013), ΔP/I (- 0.05 [- 0.09, - 0.03] vs - 0.02 [- 0.04, 0.01], P = 0.026)were remarkably enhanced compared to those of the metformin therapy. The expression of 8-OH-dG, 8-iso-PGF2α and hs-CRP also decreased after 8-week metformin treatment. CONCLUSIONS These data demonstrated that liraglutide administration was more effective on ameliorating beta-cell function than metformin treatment in young patients with new-onset type 2 diabetes mellitus. Both liraglutide and metformin could alleviate the level of oxidative stress and attenuate low grade inflammatory, we speculate this effect may not the main mechanism of beta-cell function improvement by liraglutide in diabetic patients.Trial registration Chinese Clinical Trials registry, chiCTR1800018008, Registered 27 August 2018-retrospectively registered.
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Affiliation(s)
- Wen-qiang Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital Xiamen University, 201-209 Hubin South Road, Xiamen, 361004 China
| | - Yuan Tian
- Department of Endocrinology and Metabolism, Zhongshan Hospital Xiamen University, 201-209 Hubin South Road, Xiamen, 361004 China
| | - Xiao-min Chen
- Department of Endocrinology and Metabolism, Zhongshan Hospital Xiamen University, 201-209 Hubin South Road, Xiamen, 361004 China
| | - Li-fen Wang
- Guangzhou Medicine University Second Affiliated Hospital, 250-296 Changgang East Road, Guangzhou, 510260 China
| | - Chan-chan Chen
- Department of Endocrinology and Metabolism, Zhongshan Hospital Xiamen University, 201-209 Hubin South Road, Xiamen, 361004 China
| | - Chuan-mei Qiu
- Department of Endocrinology and Metabolism, Zhongshan Hospital Xiamen University, 201-209 Hubin South Road, Xiamen, 361004 China
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Schmid V, Wagner R, Sailer C, Fritsche L, Kantartzis K, Peter A, Heni M, Häring HU, Stefan N, Fritsche A. Non-alcoholic fatty liver disease and impaired proinsulin conversion as newly identified predictors of the long-term non-response to a lifestyle intervention for diabetes prevention: results from the TULIP study. Diabetologia 2017; 60:2341-2351. [PMID: 28840257 DOI: 10.1007/s00125-017-4407-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Accepted: 07/11/2017] [Indexed: 02/08/2023]
Abstract
AIMS/HYPOTHESIS Lifestyle intervention is effective to prevent type 2 diabetes. However, a considerable long-term non-response occurs to a standard lifestyle intervention. We investigated which risk phenotypes at baseline and their changes during the lifestyle intervention predict long-term glycaemic non-response to the intervention. METHODS Of 300 participants at high risk for type 2 diabetes who participated in a 24 month lifestyle intervention with diet modification and increased physical activity, 190 participants could be re-examined after 8.7 ± 1.6 years. All individuals underwent a five-point 75 g OGTT and measurements of body fat compartments and liver fat content with MRI and spectroscopy at baseline, 9 and 24 months during the lifestyle intervention, and at long-term follow-up. Fasting proinsulin to insulin conversion (PI/I ratio) and insulin sensitivity and secretion were calculated from the OGTT. Non-response to lifestyle intervention was defined as no decrease in glycaemia, i.e. no decrease in AUC for glucose at 0-120 min during OGTT (AUCglucose0-120 min). RESULTS Before the lifestyle intervention, 56% of participants had normal glucose regulation and 44% individuals had impaired fasting glucose and/or impaired glucose tolerance. At long-term follow-up, 11% had developed diabetes. Multivariable regression analysis with adjustment for age, sex, BMI and change in BMI during the lifestyle intervention revealed that baseline insulin secretion and insulin sensitivity, as well as change in insulin sensitivity during the lifestyle intervention, predicted long-term glycaemic control after 9 years. In addition, increased hepatic lipid content as well as impaired fasting proinsulin conversion at baseline were newly detected phenotypes that independently predicted long-term glycaemic control. CONCLUSIONS/INTERPRETATION Increased hepatic lipid content and impaired proinsulin conversion are new predictors, independent of change in body weight, for non-response to lifestyle intervention in addition to the confirmed factors, impaired insulin secretion and insulin sensitivity.
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Affiliation(s)
- Vera Schmid
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
- International Research Training Group 1302, University of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
| | - Robert Wagner
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Corinna Sailer
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Louise Fritsche
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Konstantinos Kantartzis
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Andreas Peter
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Martin Heni
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Hans-Ulrich Häring
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Norbert Stefan
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Andreas Fritsche
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany.
- German Centre for Diabetes Research (DZD), Tübingen, Germany.
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Ferjan S, Janez A, Jensterle M. DPP4 INHIBITOR SITAGLIPTIN AS A POTENTIAL TREATMENT OPTION IN METFORMIN-INTOLERANT OBESE WOMEN WITH POLYCYSTIC OVARY SYNDROME: A PILOT RANDOMIZED STUDY. Endocr Pract 2017; 24:69-77. [PMID: 29144805 DOI: 10.4158/ep-2017-0027] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
OBJECTIVE Metformin has an established role in the management of polycystic ovary syndrome (PCOS). Some patients cannot tolerate it due to associated gastrointestinal adverse events. The present study evaluated the dipeptidyl peptidase 4 inhibitor sitagliptin as a potential treatment option in metformin-intolerant PCOS. METHODS We conducted a 12-week, prospective, randomized, open-label study with 30 obese metformin-intolerant women with PCOS (age 35.0 ± 7.2 years; body mass index, 36.9 ± 5.5 kg/m2). After metformin withdrawal, they were randomized to lifestyle intervention and sitagliptin 100 mg daily (SITA) or lifestyle intervention alone as controls (CON). All participants underwent anthropometric and endocrine measurements and oral glucose tolerance testing. Model-derived indexes of insulin resistance and beta-cell function were calculated. RESULTS SITA improved beta-cell function as assessed by the homeostasis model assessment for beta-cell function index (HOMA-B) of 45.9 ± 35.8 ( P = .001), modified beta-cell function index (MBCI) of 7.9 ± 7 ( P = .002), and quantitative insulin-sensitivity check index (QUICKI) of -0.03 ± 0.03 ( P = .002). By contrast, beta-cell function decreased in CON. The between-group differences were significant for HOMA-B ( P = 0.001), MBCI ( P = .010), and QUICKI ( P = .025). The conversion rate to impaired glucose homeostasis was prevented in SITA: 3 of 15 subjects had impaired glucose tolerance (IGT) before and after the study. In CON, none had type 2 diabetes (T2D), and 4 had IGT at the beginning. After 12 weeks, IGT was observed in 2 and T2D in 3 subjects. CONCLUSION SITA improved beta-cell function and prevented a conversion to IGT and T2D in metformin-intolerant obese PCOS patients. ABBREVIATIONS BMI = body mass index; DPP-4 = dipeptidyl peptidase-4; DXA = dual energy X-ray absorptiometry; GIP = glucose-dependent insulinotropic peptide; GLP-1 = glucagon-like peptide-1; HOMA-B = homeostasis model assessment for beta-cell function; HOMA-IR = homeostasis model assessment of insulin resistance; IAI = insulin action index; IGT = impaired glucose tolerance; IR = insulin resistance; MBCI = modified beta-cell function index; OGTT = oral glucose tolerance test; QUICKI = quantitative insulin sensitivity check index; PCOS = polycystic ovary syndrome; SHBG = sex hormone-binding globulin; T2D = type 2 diabetes.
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20
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de Mello VD, Lankinen MA, Lindström J, Puupponen-Pimiä R, Laaksonen DE, Pihlajamäki J, Lehtonen M, Uusitupa M, Tuomilehto J, Kolehmainen M, Törrönen R, Hanhineva K. Fasting serum hippuric acid is elevated after bilberry (Vaccinium myrtillus) consumption and associates with improvement of fasting glucose levels and insulin secretion in persons at high risk of developing type 2 diabetes. Mol Nutr Food Res 2017; 61. [PMID: 28556578 DOI: 10.1002/mnfr.201700019] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 04/20/2017] [Accepted: 05/08/2017] [Indexed: 01/23/2023]
Abstract
SCOPE Urinary hippuric acid has been proposed as a biomarker for fruit, vegetable, and polyphenol consumption. We assessed how serum hippuric acid changes after a bilberry-enriched diet (BB; high anthocyanin intake) and another berry diet including strawberries, raspberries, and cloudberries (SRC; lower anthocyanin intake) and how these changes associate with insulin and glucose metabolism. METHODS AND RESULTS Hippuric acid was measured with LC-QTOF-MS metabolite profiling analysis from fasting serum samples at baseline and after an 8-week intervention in 47 individuals with features of the metabolic syndrome who were randomized to either a BB diet (n = 15), an SRC diet (n = 20) or a control diet (n = 12). Fasting serum hippuric acid increased significantly (3.5-fold, p = 0.001) only in the BB group and correlated with changes in fasting plasma glucose concentration (r = -0.54, p < 0.05) and insulin secretion (r = 0.59, p < 0.05). These associations were confirmed in the Finnish Diabetes Prevention Study (n = 198). CONCLUSION Fasting serum hippuric acid is increased after consumption of anthocyanin-rich bilberries, and may contribute to the beneficial effect of bilberry consumption through its associations with better glycemic control and β-cell function.
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Affiliation(s)
- Vanessa Df de Mello
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Maria A Lankinen
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Jaana Lindström
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
| | | | - David E Laaksonen
- Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital, Finland
| | - Jussi Pihlajamäki
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.,Clinical Nutrition and Obesity Center, Kuopio University Hospital, Finland
| | - Marko Lehtonen
- School of Pharmacy, University of Eastern Finland, Kuopio, Finland.,LC-MS Metabolomics Center, Biocenter Kuopio, Kuopio, Finland
| | - Matti Uusitupa
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.,Research Unit, Kuopio University Hospital, Kuopio, Finland
| | - Jaakko Tuomilehto
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.,Center for Vascular Prevention, Danube-University Krems, Austria.,Saudi Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Marjukka Kolehmainen
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Riitta Törrönen
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Kati Hanhineva
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.,LC-MS Metabolomics Center, Biocenter Kuopio, Kuopio, Finland
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Kabadi UM. Major Pathophysiology in Prediabetes and Type 2 Diabetes: Decreased Insulin in Lean and Insulin Resistance in Obese. J Endocr Soc 2017; 1:742-750. [PMID: 29264527 PMCID: PMC5686647 DOI: 10.1210/js.2016-1116] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2016] [Accepted: 05/05/2017] [Indexed: 01/30/2023] Open
Abstract
CONTEXT Lowering of body mass index (BMI) to ≥25 kg/m2 as obesity by ADA suggests insulin resistance as a major mechanism of impaired glucose metabolism (IGM) in Asians. However, glimepiride, an insulin secretagogue, delayed onset of type 2 diabetes (DM2) from prediabetes (PreDM), indicating decreased insulin secretion (IS) as a major factor in lean (L; BMI < 27 kg/m2) subjects with IGM. OBJECTIVE Assessment of IS and insulin resistance (IR) in L and obese (Ob; BMI ≥ 27 kg/m2) subjects with euglycemia (N), PreDM, and new onset DM2. SUBJECTS Seventy-five men and 45 women ages 36 to 75 years were divided into six groups: LN, LPreDM, LDM2, ObN, ObPreDM, and ObDM2. METHODS Determination of IS by insulinogenic indices (I/G) at fasting (FI/FG), first phase (∆I/∆G), and cumulative responses over 2 hours of OGTT (CRI/CRG), and IR by FIXFG, ∆IX∆G, and CRIXCRG. Changes in IS and IR for PreDM and DM2 were calculated as % fall and % rise, respectively, from levels in N. RESULTS All indices of IS and IR were lower (P < 0.05) in L than corresponding Ob groups (P < 0.05). Moreover, decline in IS and rise in IR were progressive from N to PreDM (P < 0.05) and DM2 (P < 0.05) in both groups. However, the declines in IS were greater (P < 0.05) than rises in IR in LPreDM and LDM2. Whereas, the rises in IR were higher (P < 0.05) than declines in IS in ObPreDM and ObDM2. CONCLUSION In L, major mechanism of IGM is declining IS and not rising IR documented among Ob.
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Affiliation(s)
- Udaya M Kabadi
- VA Medical Center, Des Moines, Iowa 50310
- University of Iowa, Iowa City, Iowa 52242
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22
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Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study. Sci Rep 2017; 7:46337. [PMID: 28397877 PMCID: PMC5387722 DOI: 10.1038/srep46337] [Citation(s) in RCA: 232] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Accepted: 03/15/2017] [Indexed: 02/06/2023] Open
Abstract
Wide-scale profiling technologies including metabolomics broaden the possibility of novel discoveries related to the pathogenesis of type 2 diabetes (T2D). By applying non-targeted metabolomics approach, we investigated here whether serum metabolite profile predicts T2D in a well-characterized study population with impaired glucose tolerance by examining two groups of individuals who took part in the Finnish Diabetes Prevention Study (DPS); those who either early developed T2D (n = 96) or did not convert to T2D within the 15-year follow-up (n = 104). Several novel metabolites were associated with lower likelihood of developing T2D, including indole and lipid related metabolites. Higher indolepropionic acid was associated with reduced likelihood of T2D in the DPS. Interestingly, in those who remained free of T2D, indolepropionic acid and various lipid species were associated with better insulin secretion and sensitivity, respectively. Furthermore, these metabolites were negatively correlated with low-grade inflammation. We replicated the association between indolepropionic acid and T2D risk in one Finnish and one Swedish population. We suggest that indolepropionic acid, a gut microbiota-produced metabolite, is a potential biomarker for the development of T2D that may mediate its protective effect by preservation of β-cell function. Novel lipid metabolites associated with T2D may exert their effects partly through enhancing insulin sensitivity.
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23
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Cefalu WT, Buse JB, Tuomilehto J, Fleming GA, Ferrannini E, Gerstein HC, Bennett PH, Ramachandran A, Raz I, Rosenstock J, Kahn SE. Update and Next Steps for Real-World Translation of Interventions for Type 2 Diabetes Prevention: Reflections From a Diabetes Care Editors' Expert Forum. Diabetes Care 2016; 39:1186-201. [PMID: 27631469 PMCID: PMC4915559 DOI: 10.2337/dc16-0873] [Citation(s) in RCA: 109] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The International Diabetes Federation estimates that 415 million adults worldwide now have diabetes and 318 million have impaired glucose tolerance. These numbers are expected to increase to 642 million and 482 million, respectively, by 2040. This burgeoning pandemic places an enormous burden on countries worldwide, particularly resource-poor regions. Numerous landmark trials evaluating both intensive lifestyle modification and pharmacological interventions have persuasively demonstrated that type 2 diabetes can be prevented or its onset can be delayed in high-risk individuals with impaired glucose tolerance. However, key challenges remain, including how to scale up such approaches for widespread translation and implementation, how to select appropriately from various interventions and tailor them for different populations and settings, and how to ensure that preventive interventions yield clinically meaningful, cost-effective outcomes. In June 2015, a Diabetes Care Editors' Expert Forum convened to discuss these issues. This article, an outgrowth of the forum, begins with a summary of seminal prevention trials, followed by a discussion of considerations for selecting appropriate populations for intervention and the clinical implications of the various diagnostic criteria for prediabetes. The authors outline knowledge gaps in need of elucidation and explore a possible new avenue for securing regulatory approval of a prevention-related indication for metformin, as well as specific considerations for future pharmacological interventions to delay the onset of type 2 diabetes. They conclude with descriptions of some innovative, pragmatic translational initiatives already under way around the world.
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Affiliation(s)
- William T. Cefalu
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
| | - John B. Buse
- University of North Carolina School of Medicine, Chapel Hill, NC
| | - Jaakko Tuomilehto
- Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland; Dasman Diabetes Institute, Dasman, Kuwait; Saudi Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia; and Center for Vascular Prevention, Danube University Krems, Krems, Austria
| | | | | | | | | | - Ambady Ramachandran
- India Diabetes Research Foundation and Dr. A. Ramachandran’s Diabetes Hospitals, Chennai, India
| | - Itamar Raz
- Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Julio Rosenstock
- Dallas Diabetes and Endocrine Center at Medical City and The University of Texas Southwestern Medical Center, Dallas, TX
| | - Steven E. Kahn
- VA Puget Sound Health Care System and University of Washington, Seattle, WA
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Ram J, Snehalatha C, Selvam S, Nanditha A, Shetty AS, Godsland IF, Johnston DG, Ramachandran A. The oral disposition index is a strong predictor of incident diabetes in Asian Indian prediabetic men. Acta Diabetol 2015; 52:733-41. [PMID: 25670243 DOI: 10.1007/s00592-015-0718-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2014] [Accepted: 01/27/2015] [Indexed: 10/24/2022]
Abstract
AIMS In this analysis, we sought to examine the prospective association of the disposition index (DIo) derived from oral glucose tolerance test with incident diabetes in Asian Indian men with impaired glucose tolerance (IGT). METHODS These post hoc analyses used data from a 2-year prospective study in primary prevention of diabetes using lifestyle intervention among 517 men with IGT. All the participants received standard lifestyle advice at baseline. The surrogate insulin sensitivity and insulin secretion measures were tested for their hyperbolic relationship. Predictive associations of various surrogate measures with incident diabetes were determined using receiver operating characteristic curves. RESULTS The combination of total area under the curve of insulin-to-glucose ratio (AUCinsulin/glucose) and Matsuda's insulin sensitivity index was the best equation to depict DIo [β: -0.954 (95 % CI -1.015 to -0.893)] compared to other measures tested in this cohort. There was an inverse association between change in DIo at the final follow-up and development of incident diabetes. Among the surrogate insulin measures studied, DIo [AUC (0.717 (95 % CI 0.675-0.756))] as a composite measure was superior than other surrogate indices. CONCLUSIONS Among the surrogate indices studied, DIo was the best measure associated with incident diabetes.
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Affiliation(s)
- Jagannathan Ram
- India Diabetes Research Foundation, Dr. A. Ramachandran's Diabetes Hospitals, 28 Marshalls Road, Egmore, Chennai, 600008, India
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de Mello VDF, Lindström J, Eriksson JG, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Pihlajamäki J, Tuomilehto J, Uusitupa M. Markers of cholesterol metabolism as biomarkers in predicting diabetes in the Finnish Diabetes Prevention Study. Nutr Metab Cardiovasc Dis 2015; 25:635-642. [PMID: 25921846 DOI: 10.1016/j.numecd.2015.03.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Revised: 03/19/2015] [Accepted: 03/23/2015] [Indexed: 01/15/2023]
Abstract
BACKGROUND AND AIMS We examined the effect of serum markers of cholesterol synthesis and absorption on the incidence of type 2 diabetes (T2D) in the randomized Finnish Diabetes Prevention Study (DPS). We also explored a possible interaction of ABCG8 rs4299376 on sterol levels and lifestyle intervention. METHODS AND RESULTS We conducted a prospective cohort study including overweight, middle-aged people with impaired glucose tolerance at baseline who participated in the randomized DPS. The primary outcome of the DPS was the diagnosis of T2D based on repeated oral glucose tolerance tests (OGTTs). After active intervention (median of four years, 1994-2001), non-T2D participants were further followed until T2D diagnosis, dropout or the end of 2009. Of these, 340 participants who had β-sitosterol, campesterol, lathosterol and desmosterol measured by gas chromatography-mass spectrometry during the active four-year follow-up and who were not using cholesterol lowering medications were analysed. Surrogate indexes of insulin sensitivity (IS) and secretion were calculated from an OGTT. In adjusted models, plant sterols during the four-year follow-up were associated with lower T2D incidence during the extended eight-year follow-up (HR for 1-SD change in β-sitosterol and campesterol: 0.76 [0.63-0.92], and 0.81 [0.67-0.99], respectively). Lathosterol levels were associated with higher T2D incidence (HR: 1.35 [1.13-1.62]). These associations, though, were not independent of IS. There was an interaction between rs4299376 and study group on β-sitosterol (p = 0.001) and campesterol (p = 0.004) levels during the follow-up. CONCLUSIONS Markers of low absorption and high synthesis of cholesterol were associated with the risk of developing T2D, mostly ascribed to IS.
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Affiliation(s)
- V D F de Mello
- Institute of Public Health and Clinical Nutrition, Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
| | - J Lindström
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
| | - J G Eriksson
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland; Department of General Practice and Primary Health, University of Helsinki, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland; Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland; Vaasa Central Hospital, Vaasa, Finland
| | - P Ilanne-Parikka
- The Diabetes Centre, Finnish Diabetes Association, Tampere, Finland; Science Center, Tampere University Hospital, Tampere, Finland
| | - S Keinänen-Kiukaanniemi
- Institute of Health Sciences, University of Oulu, Oulu, Finland; Unit of General Practice, Oulu University Hospital and Oulu Health Centre, Oulu, Finland
| | - J Pihlajamäki
- Institute of Public Health and Clinical Nutrition, Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Clinical Nutrition and Obesity Center, Kuopio University Hospital, Finland
| | - J Tuomilehto
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland; Center for Vascular Prevention, Danube-University Krems, Austria
| | - M Uusitupa
- Institute of Public Health and Clinical Nutrition, Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Research Unit, Kuopio University Hospital, Kuopio, Finland
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Takkunen MJ, Schwab US, de Mello VDF, Eriksson JG, Lindström J, Tuomilehto J, Uusitupa MIJ. Longitudinal associations of serum fatty acid composition with type 2 diabetes risk and markers of insulin secretion and sensitivity in the Finnish Diabetes Prevention Study. Eur J Nutr 2015; 55:967-79. [DOI: 10.1007/s00394-015-0911-4] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Accepted: 04/22/2015] [Indexed: 01/08/2023]
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27
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Ekström N, Svensson AM, Miftaraj M, Andersson Sundell K, Cederholm J, Zethelius B, Eliasson B, Gudbjörnsdottir S. Durability of oral hypoglycemic agents in drug naïve patients with type 2 diabetes: report from the Swedish National Diabetes Register (NDR). BMJ Open Diabetes Res Care 2015; 3:e000059. [PMID: 25815205 PMCID: PMC4368982 DOI: 10.1136/bmjdrc-2014-000059] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Revised: 02/19/2015] [Accepted: 02/20/2015] [Indexed: 11/05/2022] Open
Abstract
OBJECTIVE To analyze the durability of monotherapy with different classes of oral hypoglycemic agents (OHAs) in drug naïve patients with type 2 diabetes mellitus (T2DM) in real life. METHODS Men and women with T2DM, who were new users of OHA monotherapy and registered in the Swedish National Diabetes Register July 2005-December 2011, were available (n=17 309) and followed for up to 5.5 years. Time to monotherapy failure, defined as discontinuation of continuous use with the initial agent, switch to a new agent, or add-on treatment of a second agent, was analyzed as a measure of durability. Baseline characteristics were balanced by propensity score matching 1:5 between groups of sulfonylurea (SU) versus metformin (n=4303) and meglitinide versus metformin (n=1308). HRs with 95% CIs were calculated using Cox regression models. RESULTS SU and meglitinide, as compared with metformin, were associated with increased risk of monotherapy failure (HR 1.74; 95% CI 1.56 to 1.94 and 1.66; 1.37 to 2.00 for SU and meglitinide, respectively). When broken down by type of monotherapy failure, SU and meglitinide were associated with an increased risk of add-on treatment of a second agent (HR 3.14; 95% CI 2.66 to 3.69 and 2.52; 1.89 to 3.37 for SU and meglitinide, respectively) and of switch to a new agent (HR 2.81; 95% CI 2.01 to 3.92 and 3.78; 2.25 to 6.32 for SU and meglitinide, respectively). The risk of discontinuation did not differ significantly between the groups. CONCLUSIONS In this nationwide observational study reflecting clinical practice, SU and meglitinide showed substantially increased risk of switch to a new agent or add on of a second agent compared with metformin. These results indicate superior glycemic durability with metformin compared with SU and also meglitinide in real life.
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Affiliation(s)
- Nils Ekström
- Department of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | | | | | | | - Jan Cederholm
- Department of Public Health and Caring Sciences/Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden
| | - Björn Zethelius
- Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden
- Medical Products Agency, Uppsala, Sweden
| | - Björn Eliasson
- Department of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Soffia Gudbjörnsdottir
- Department of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
- Centre of Registers in Region Västra Götaland, Göteborg, Sweden
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Soriguer F, Colomo N, Valdés S, Goday A, Rubio-Martín E, Esteva I, Castaño L, Ruiz de Adana MS, Morcillo S, Calle A, García-Fuentes E, Catalá M, Gutiérrez-Repiso C, Delgado E, Gomis R, Ortega E, Rojo-Martínez G. Modifications of the homeostasis model assessment of insulin resistance index with age. Acta Diabetol 2014; 51:917-25. [PMID: 24687694 DOI: 10.1007/s00592-013-0523-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2013] [Accepted: 10/03/2013] [Indexed: 12/20/2022]
Abstract
The aim of the study was to analyze the association between aging and insulin resistance estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). This work involved two studies: (1) the Di@bet.es study is a cross-sectional study including 4,948 subjects, comprising a representative sample of the adult Spanish population; (2) the Pizarra study is a population-based cohort study undertaken in Pizarra (Spain), in which 1,051 subjects were evaluated at baseline and 714 completed the 6-year follow-up study. Study variables included a clinical and demographic structured survey, a lifestyle survey, a physical examination, and an oral glucose tolerance test in subjects without diabetes. In the Di@bet.es study overall, an increase occurred in blood glucose until the age of 50, after which it remained stable (data adjusted for gender, body mass index, abnormal glucose regulation [AGR]). The HOMA-IR increased significantly with age (p = 0.01), due to a higher prevalence of obesity (p < 0.0001) and AGR (p < 0.001). In non-obese subjects without AGR, HOMA-IR values were not modified with age (p = 0.30), but they were with body mass index (p < 0.001). In the Pizarra study, the HOMA-IR was significantly lower after 6-year follow-up in the whole study population. Subjects with a HOMA-IR level higher than the 75th percentile at baseline were more likely to develop diabetes (OR 2.2, 95 % CI 1.2-3.9; p = 0.007) than subjects with a lower HOMA-IR. We concluded that age per se did not increase HOMA-IR levels, changes that might be related to higher rates of obesity and AGR in older subjects. The HOMA-IR was associated with an increased risk of developing type 2 diabetes 6 years later.
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Affiliation(s)
- Federico Soriguer
- Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Barcelona, Spain
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29
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Nanditha A, Ram J, Snehalatha C, Selvam S, Priscilla S, Shetty AS, Arun R, Godsland IF, Johnston DG, Ramachandran A. Early improvement predicts reduced risk of incident diabetes and improved cardiovascular risk in prediabetic Asian Indian men participating in a 2-year lifestyle intervention program. Diabetes Care 2014; 37:3009-15. [PMID: 25216506 DOI: 10.2337/dc14-0407] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Objectives of this ancillary analysis of a prospective, prevention study among Asian Indians with impaired glucose tolerance (IGT) were a) to quantify the reduction in incident diabetes at 24 months in participants who achieved normal glucose tolerance (NGT) at 6 months (NGT-6 m) compared with the other participants, b) the factors influencing the reversal to NGT at the end of the study at 24 months (NGT-24 m), and c) to assess changes in cardiometabolic risk factors in different categories of dysglycemia at 24 months. RESEARCH DESIGN AND METHODS Data from a 2-year primary prevention trial were used. Effect of reversion to NGT-6 m on incidence of type 2 diabetes mellitus (T2DM) was analyzed using the Cox proportional hazards model. Predictive variables for reversal to NGT were identified using multiple logistic regression analysis. Changes in cardiometabolic risk factors were estimated according to the final glycemic status using fixed-effect, mixed-linear regression modeling. RESULTS The risk of T2DM in 2 years was lower by 75% in NGT-6 m group (hazard ratio 0.25 [95% CI 0.12-0.52]). Predictive variables for reversal to NGT-24 m were good baseline β-cell function (odds ratio [OR] 2.79 [95% CI 2.30-3.40]) and its further improvement (OR 5.70 [95% CI 4.58-7.08]), and NGT-6 m (OR 2.10 [95% CI 1.14-3.83]). BMI decreased in those who reverted to NGT. Deterioration to T2DM was associated with an increase in the levels of cardiometabolic risk factors. CONCLUSIONS Early reversion to NGT by lifestyle intervention in prediabetic men was associated with a significant reduction in subsequent incidence of diabetes. Good baseline β-cell function and its further improvement and NGT-6 m were associated with reversion to NGT-24 months. Reversion to NGT was associated with modest improvements, whereas conversion to T2DM was associated with significant worsening of the cardiometabolic risk profile.
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Affiliation(s)
- Arun Nanditha
- India Diabetes Research Foundation and Dr. A. Ramachandran's Diabetes Hospitals, Chennai, India
| | - Jagannathan Ram
- India Diabetes Research Foundation and Dr. A. Ramachandran's Diabetes Hospitals, Chennai, India
| | - Chamukuttan Snehalatha
- India Diabetes Research Foundation and Dr. A. Ramachandran's Diabetes Hospitals, Chennai, India
| | - Sundaram Selvam
- India Diabetes Research Foundation and Dr. A. Ramachandran's Diabetes Hospitals, Chennai, India
| | - Susairaj Priscilla
- India Diabetes Research Foundation and Dr. A. Ramachandran's Diabetes Hospitals, Chennai, India
| | - Ananth Samith Shetty
- India Diabetes Research Foundation and Dr. A. Ramachandran's Diabetes Hospitals, Chennai, India
| | - Raghavan Arun
- India Diabetes Research Foundation and Dr. A. Ramachandran's Diabetes Hospitals, Chennai, India
| | - Ian F Godsland
- Faculties of Medicine and Engineering, Imperial College, London, U.K
| | | | - Ambady Ramachandran
- India Diabetes Research Foundation and Dr. A. Ramachandran's Diabetes Hospitals, Chennai, India
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Russo GT, Giorda CB, Cercone S, Nicolucci A, Cucinotta D. Factors associated with beta-cell dysfunction in type 2 diabetes: the BETADECLINE study. PLoS One 2014; 9:e109702. [PMID: 25347846 PMCID: PMC4210056 DOI: 10.1371/journal.pone.0109702] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Accepted: 09/11/2014] [Indexed: 12/22/2022] Open
Abstract
Aims Beta-cell dysfunction is an early event in the natural history of type 2 diabetes. However, its progression is variable and potentially influenced by several clinical factors. We report the baseline data of the BetaDecline study, an Italian prospective multicenter study on clinical predictors of beta-cell dysfunction in type 2 diabetes. Materials and Methods Clinical, lifestyle, and laboratory data, including circulating levels of inflammatory markers and non-esterified fatty acids, were collected in 507 type 2 diabetic outpatients on stable treatment with oral hypoglycemic drugs or diet for more than 1 year. Beta-cell dysfunction was evaluated by calculating the proinsulin/insulin ratio (P/I). Results At baseline, the subjects in the upper PI/I ratio quartile were more likely to be men and receiving secretagogue drugs; they also showed a borderline longer diabetes duration (P = 0.06) and higher serum levels of glycated hemoglobin (HbA1c), fasting blood glucose, and triglycerides. An inverse trend across all PI/I quartiles was noted for BMI and serum levels of total cholesterol (T-C), LDL-C, HDL-C and C reactive protein (CRP), and with homeostatic model assessment (HOMA-B) and HOMA of insulin resistance (HOMA-IR) values (P<0.05 for all). At multivariate analysis, the risk of having a P/I ratio in the upper quartile was higher in the subjects on secretagogue drugs (odds ratio [OR] 4.2; 95% confidence interval [CI], 2.6–6.9) and in the males (OR 1.8; 95% CI, 1.1–2.9). Conclusions In the BetaDecline study population, baseline higher PI/I values, a marker of beta-cell dysfunction, were more frequent in men and in patients on secretagogues drugs. Follow-up of this cohort will allow the identification of clinical predictors of beta-cell failure in type 2 diabetic outpatients.
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Affiliation(s)
- Giuseppina T. Russo
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
- * E-mail:
| | | | | | - Antonio Nicolucci
- Department of Clinical Pharmacology and Epidemiology Fondazione Mario Negri Sud, S. Maria Imbaro, Italy
| | - Domenico Cucinotta
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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Peirson L, Douketis J, Ciliska D, Fitzpatrick-Lewis D, Ali MU, Raina P. Treatment for overweight and obesity in adult populations: a systematic review and meta-analysis. CMAJ Open 2014; 2:E306-17. [PMID: 25485258 PMCID: PMC4251513 DOI: 10.9778/cmajo.20140012] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Obesity is a major public health issue. This review updates the evidence on the effectiveness of behavioural and pharmacologic treatments for overweight and obesity in adults. METHODS We updated the search conducted in a previous review. Randomized trials of primary-care-relevant behavioural (diet, exercise and lifestyle) and pharmacologic (orlistat and metformin) with or without behavioural treatments in overweight and obese adults were included if 12-month, postbaseline data were provided for weight outcomes. Studies reporting harms were included regardless of design. Data were extracted and pooled wherever possible for 5 weight outcomes, 6 secondary health outcomes and 4 adverse events categories. RESULTS We identified 68 studies, most consisted of short-term (≤ 12 mo) treatments using diet (n = 8), exercise (n = 4), diet and exercise (n = 10), lifestyle (n = 19), orlistat (n = 25) or metformin (n = 4). Compared with the control groups, intervention participants had a greater weight loss of -3.02 kg (95% confidence interval [CI] -3.52 to -2.52), a greater reduction in waist circumference of -2.78 cm (95% CI -3.34 to -2.22) and a greater reduction in body mass index of -1.11 kg/m(2) (95% CI -1.39 to -0.84). The relative risk for loss of ≥ 5% body weight was 1.77 (95% CI 1.58-1.99, [number needed to treat 5, 95% CI 4-7]), and the relative risk for loss of ≥ 10% body weight was 1.91 (95% CI 1.69-2.16, [number needed to treat 9, 95% CI 7-12]). Incidence of type 2 diabetes was lower among pre-diabetic intervention participants (relative risk 0.62 [95% CI 0.50-0.77], number needed to treat 17 [95% CI 13-29]). With prevalence rates for type 2 diabetes on the rise, weight loss coupled with a reduction in the incidence of type 2 diabetes could potentially have a significant benefit on population health and a possible reduction in need for drug treatments for glycemic control. INTERPRETATION There is moderate quality evidence that behavioural and pharmacologic plus behvioural, treatments for overweight and obesity in adults lead to clinically important reductions in weight and incidence of type 2 diabetes in pre-diabetic populations. REGISTRATION PROSPERO no. CRD42012002753.
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Affiliation(s)
- Leslea Peirson
- McMaster Evidence Review and Synthesis Centre, McMaster University Hamilton, Ont
| | - James Douketis
- Department of Medicine, McMaster University, Hamilton, Ont
- St. Joseph’s HealthCare, Hamilton, Ont
| | - Donna Ciliska
- McMaster Evidence Review and Synthesis Centre, McMaster University Hamilton, Ont
| | | | - Muhammad Usman Ali
- McMaster Evidence Review and Synthesis Centre, McMaster University Hamilton, Ont
| | - Parminder Raina
- McMaster Evidence Review and Synthesis Centre, McMaster University Hamilton, Ont
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Ferrannini E, Mari A. β-Cell function in type 2 diabetes. Metabolism 2014; 63:1217-27. [PMID: 25070616 DOI: 10.1016/j.metabol.2014.05.012] [Citation(s) in RCA: 93] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Revised: 05/09/2014] [Accepted: 05/25/2014] [Indexed: 01/09/2023]
Abstract
Different in vivo tests explore different aspects of β-cell function. Because intercorrelation of insulin secretion indices is modest, no single in vivo test allows β-cell function to be assessed with accuracy and specificity comparable to insulin sensitivity. Physiologically-based mathematical modeling is necessary to interpret insulin secretory responses in terms of relevant parameters of β-cell function. Models can be used to analyze intravenous glucose tests, but secretory responses to intravenous glucose may be paradoxical in subjects with diabetes. Use of oral glucose (or mixed meal) data may be preferable not only for simplicity but also for physiological interpretation. While the disposition index focuses on the relationship between insulin secretion and insulin resistance, secretion parameters reflecting the dynamic response to changing glucose levels over a time frame of minutes or hours--such as β-cell glucose sensitivity--are key to explain changes in glucose tolerance and are largely independent of insulin sensitivity. Pathognomonic of the β-cell defect of type 2 diabetes is a reduced glucose sensitivity, which is accompanied by normal or raised absolute insulin secretion rates--compensatory to the attendant insulin resistance--and impaired incretin-induced potentiation. As β-cell mass is frequently within the range of nondiabetic individuals, these defects are predominantly functional and potentially reversible. Any intervention, on lifestyle or with drugs, that improves glucose tolerance does so primarily through increased β-cell glucose sensitivity. So far, however, no intervention has proven unequivocally capable of modifying the natural course of β-cell dysfunction.
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Affiliation(s)
- Ele Ferrannini
- Department of Clinical & Experimental Medicine, University of Pisa, Italy.
| | - Andrea Mari
- C N R Institute of Biomedical Engineering, Padova, Italy
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33
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Diet, insulin secretion and insulin sensitivity--the Dose-Responses to Exercise Training (DR's EXTRA) Study (ISRCTN45977199). Br J Nutr 2014; 112:1530-41. [PMID: 25230681 DOI: 10.1017/s0007114514002426] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Intakes of saturated fat (SF) and dietary fibre, body mass and physical activity are all associated with the incidence of type 2 diabetes mellitus. Their relative importance for the maintenance of normal glucose metabolism is not fully known. In a population-based sample of 1114 individuals, aged 58-78 years, dietary intakes were assessed by 4 d food records and cardiorespiratory fitness as maximal oxygen uptake. Insulin secretion, insulin sensitivity, the early-phase disposition index (DI30) and the total disposition index (DI120) were assessed based on an oral glucose tolerance test. Linear associations were modelled using linear regression. Combined effects were studied by introducing SF and fibre intakes, as well as cardiorespiratory fitness and waist circumference (WC) as dichotomised variables in general linear models. Intakes of dietary fibre and whole-grain bread were positively associated with insulin sensitivity, independent of physical fitness and WC. In women, dietary fibre intake was also positively associated with DI30. The negative association of high WC with DI30 was attenuated by a combination of low SF intake and high cardiorespiratory fitness. In conclusion, dietary fibre and a combination of low SF intake and high cardiorespiratory fitness may contribute to the maintenance of normal glucose metabolism, independent of WC.
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34
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Brazeau AS, Leong A, Meltzer SJ, Cruz R, DaCosta D, Hendrickson-Nelson M, Joseph L, Dasgupta K. Group-based activities with on-site childcare and online support improve glucose tolerance in women within 5 years of gestational diabetes pregnancy. Cardiovasc Diabetol 2014; 13:104. [PMID: 24981579 PMCID: PMC4227099 DOI: 10.1186/1475-2840-13-104] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Accepted: 04/26/2014] [Indexed: 11/24/2022] Open
Abstract
Background Women with gestational diabetes history are at increased risk for type 2 diabetes. They face specific challenges for behavioural changes, including childcare responsibilities. The aim of this study is to test a tailored type 2 diabetes prevention intervention in women within 5 years of a pregnancy with gestational diabetes, in terms of effects on weight and cardiometabolic risk factors. Methods The 13-week intervention, designed based on focus group discussions, included four group sessions, two with spousal participation and all with on-site childcare. Web/telephone-based support was provided between sessions. We computed mean percentage change from baseline (95% confidence intervals, CI) for anthropometric measures, glucose tolerance (75 g Oral glucose tolerance test), insulin resistance/sensitivity, blood pressure, physical activity, dietary intake, and other cardiometabolic risk factors. Results Among the 36 enrolled, 27 completed final evaluations. Most attended ≥ 3 sessions (74%), used on-site childcare (88%), and logged onto the website (85%). Steps/day (733 steps, 95% CI 85, 1391) and fruit/vegetable intake (1.5 servings/day, 95% CI 0.3, 2.8) increased. Proportions decreased for convenience meal consumption (−30%, 95% CI −50, −9) and eating out (−22%, 95% CI −44, −0) ≥ 3 times/month. Body mass index and body composition were unchanged. Fasting (−4.9%, 95% CI −9.5, −0.3) and 2-hour postchallenge (−8.0%, 95% CI −15.6, −0.5) glucose declined. Insulin sensitivity increased (ISI 0,120 23.7%, 95% CI 9.1, 38.4; Matsuda index 37.5%, 95% CI 3.5, 72.4). Insulin resistance (HOMA-IR −9.4%, 95% CI −18.6, −0.1) and systolic blood pressure (−3.3%, 95% CI −5.8, −0.8) decreased. Conclusions A tailored group intervention appears to lead to improvements in health behaviours and cardiometabolic risk factors despite unchanged body mass index and body composition. This approach merits further study. Clinical trial registration ClinicalTrials.gov (NCT01814995).
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Affiliation(s)
| | | | | | | | | | | | | | - Kaberi Dasgupta
- Division of Clinical Epidemiology, Department of Medicine, McGill University Health Centre, 687 Pine Avenue West, H3A 1A1, Montreal, Quebec, Canada.
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35
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Magnusdottir OK, Landberg R, Gunnarsdottir I, Cloetens L, Akesson B, Landin-Olsson M, Rosqvist F, Iggman D, Schwab U, Herzig KH, Savolainen MJ, Brader L, Hermansen K, Kolehmainen M, Poutanen K, Uusitupa M, Thorsdottir I, Risérus U. Plasma alkylresorcinols C17:0/C21:0 ratio, a biomarker of relative whole-grain rye intake, is associated to insulin sensitivity: a randomized study. Eur J Clin Nutr 2014; 68:453-8. [PMID: 24549027 DOI: 10.1038/ejcn.2014.12] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2013] [Revised: 12/06/2013] [Accepted: 01/04/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Few studies have used biomarkers of whole-grain intake to study its relation to glucose metabolism. We aimed to investigate the association between plasma alkylresorcinols (AR), a biomarker of whole-grain rye and wheat intake, and glucose metabolism in individuals with metabolic syndrome (MetS). SUBJECTS/METHODS Participants were 30-65 years of age, with body mass index 27-40 kg/m(2) and had MetS without diabetes. Individuals were recruited through six centers in the Nordic countries and randomized to a healthy Nordic diet (ND, n=96), rich in whole-grain rye and wheat, or a control diet (n=70), for 18-24 weeks. In addition, associations between total plasma AR concentration and C17:0/C21:0 homolog ratio as an indication of the relative whole-grain rye intake, and glucose metabolism measures from oral glucose tolerance tests were investigated in pooled (ND+control) regression analyses at 18/24 weeks. RESULTS ND did not improve glucose metabolism compared with control diet, but the AR C17:0/C21:0 ratio was inversely associated with fasting insulin concentrations (P=0.002) and positively associated with the insulin sensitivity indices Matsuda ISI (P=0.026) and disposition index (P=0.022) in pooled analyses at 18/24 weeks, even after adjustment for confounders. The AR C17:0/C21:0 ratio was not significantly associated with insulin secretion indices. Total plasma AR concentration was not related to fasting plasma glucose or fasting insulin at 18/24 weeks. CONCLUSIONS The AR C17:0/C21:0 ratio, an indicator of relative whole-grain rye intake, is associated with increased insulin sensitivity in a population with MetS.
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Affiliation(s)
- O K Magnusdottir
- 1] Unit for Nutrition Research, Landspitali-The National University Hospital of Iceland, Reykjavík, Iceland [2] Faculty of Food Science and Nutrition and School of Health Sciences, University of Iceland, Reykjavík, Iceland
| | - R Landberg
- 1] Department of Food Science, BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden [2] Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - I Gunnarsdottir
- 1] Unit for Nutrition Research, Landspitali-The National University Hospital of Iceland, Reykjavík, Iceland [2] Faculty of Food Science and Nutrition and School of Health Sciences, University of Iceland, Reykjavík, Iceland
| | - L Cloetens
- Biomedical Nutrition, Pure and Applied Biochemistry, Lund University, Lund, Sweden
| | - B Akesson
- 1] Biomedical Nutrition, Pure and Applied Biochemistry, Lund University, Lund, Sweden [2] Department of Clinical Nutrition, Skåne University Hospital, Lund, Sweden
| | - M Landin-Olsson
- Department of Endocrinology, Skåne University Hospital, Lund, Sweden
| | - F Rosqvist
- Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden
| | - D Iggman
- 1] Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden [2] Center for Clinical Research Dalarna, Falun, Sweden
| | - U Schwab
- 1] Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland [2] Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital, Kuopio, Finland
| | - K-H Herzig
- 1] Department of Physiology and Biocenter of Oulu, Institute of Biomedicine, Oulu University, Oulu, Finland [2] Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland
| | - M J Savolainen
- 1] Department of Internal Medicine and Biocenter Oulu, Institute of Clinical Medicine, University of Oulu, Oulu, Finland [2] Clinical Research Center, Oulu University Hospital, Oulu, Finland
| | - L Brader
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - K Hermansen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - M Kolehmainen
- 1] Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland [2] VTT, Technical Research Centre of Finland, Espoo and Kuopio, Kuopio, Finland
| | - K Poutanen
- 1] Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland [2] VTT, Technical Research Centre of Finland, Espoo and Kuopio, Kuopio, Finland
| | - M Uusitupa
- 1] Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland [2] Research Unit, Kuopio University Hospital, Kuopio, Finland
| | - I Thorsdottir
- 1] Unit for Nutrition Research, Landspitali-The National University Hospital of Iceland, Reykjavík, Iceland [2] Faculty of Food Science and Nutrition and School of Health Sciences, University of Iceland, Reykjavík, Iceland
| | - U Risérus
- Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden
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Herzig KH, Ahola R, Leppäluoto J, Jokelainen J, Jämsä T, Keinänen-Kiukaanniemi S. Light physical activity determined by a motion sensor decreases insulin resistance, improves lipid homeostasis and reduces visceral fat in high-risk subjects: PreDiabEx study RCT. Int J Obes (Lond) 2013; 38:1089-96. [PMID: 24285336 PMCID: PMC4125749 DOI: 10.1038/ijo.2013.224] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Revised: 11/04/2013] [Accepted: 11/13/2013] [Indexed: 11/29/2022]
Abstract
Objective: To examine physical activity (PA) thresholds affecting glucose, insulin and lipid concentrations and body fat composition in high-risk patients for type 2 diabetes (T2D). Intervention: A total of 113 subjects of both genders having abnormal glucose levels in the oral glucose tolerance test were contacted. A total of 78 subjects with age 58.8±10.4 years and body mass index 31.7±5.3 kg m−2 were randomly assigned to intervention and control groups. Intervention consisted of a supervised walking (60 min three times weekly) for 3 months. All the subjects received standard care for PA and weight reduction and wore an accelerometer during the whole wakeful time. Results: Over 80% of the daily steps clustered at an acceleration level of 0.3–0.7 g (2–3 km h−1 of walking) and were 5870 in the intervention and 4434 in the control group (P<0.029). Between 0 and 3 months no significant changes were observed in fasting and 2-h glucose, body weight or maximal oxygen uptake. In contrast, changes in fasting and 2-h insulin (−3.4 mU l−1, P=0.035 and −26.6, P=0.003, respectively), homeostasis model assessment-estimated insulin resistance (−1.0, P=0.036), total cholesterol (−0.55 mmol l−1, P=0.041), low-density lipoprotein (LDL) cholesterol (−0.36 mmol l−1, P=0.008) and visceral fat area (−5.5 cm2, P=0.030) were significantly greater in the intervention than in control subjects. The overall effects of PA were analyzed by quartiles of daily steps of all subjects. There were significant reductions in total and LDL cholesterol and visceral fat area between the highest (daily steps over 6520) and the lowest quartile (1780–2810 daily steps). The changes associated with PA remained significant after adjustments of baseline, sex, age and body weight change. Conclusion: Habitual and structured PAs with the acceleration levels of 0.3–0.7 g and daily steps over 6520, equivalent to walking at 2–3 km h−1 for 90 min daily, standing for the relative PA intensity of 30–35% of the maximal oxygen uptake, are clinically beneficial for overweight/obese and physically inactive individuals with a high risk for T2D.
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Affiliation(s)
- K-H Herzig
- 1] Institute of Biomedicine, Department of Physiology and Biocenter of Oulu, Oulu University, Oulu, Finland [2] Medical Research Center Oulu and Oulu University Hospital, Oulu, Finland
| | - R Ahola
- Department of Medical Technology, University of Oulu, Oulu, Finland
| | - J Leppäluoto
- Institute of Biomedicine, Department of Physiology and Biocenter of Oulu, Oulu University, Oulu, Finland
| | - J Jokelainen
- Institute of Health Sciences, University of Oulu, Oulu, Finland
| | - T Jämsä
- Department of Medical Technology, University of Oulu, Oulu, Finland
| | - S Keinänen-Kiukaanniemi
- 1] Institute of Health Sciences, University of Oulu, Oulu, Finland [2] Oulu University Hospital, Unit of General Practice, and Health Center of Oulu, Oulu, Finland
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Oranta O, Pahkala K, Ruottinen S, Niinikoski H, Lagström H, Viikari JSA, Jula A, Loo BM, Simell O, Rönnemaa T, Raitakari OT. Infancy-onset dietary counseling of low-saturated-fat diet improves insulin sensitivity in healthy adolescents 15-20 years of age: the Special Turku Coronary Risk Factor Intervention Project (STRIP) study. Diabetes Care 2013; 36:2952-9. [PMID: 23801725 PMCID: PMC3781523 DOI: 10.2337/dc13-0361] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE We reported previously that low-saturated-fat dietary counseling started in infancy improves insulin sensitivity in healthy children 9 years of age. The aim of this study was to evaluate the effect of lifelong dietary counseling on insulin sensitivity in healthy adolescents between 15 and 20 years of age. In addition, we examined dietary fiber intake and the polyunsaturated fatty acid (PUFA)+monounsaturated (MUFA)-to-saturated fatty acid (SFA) ratio in the intervention and control adolescents and the association of these dietary factors with homeostasis model of insulin resistance (HOMA-IR). RESEARCH DESIGN AND METHODS The study comprised adolescents participating in the randomized, controlled Special Turku Coronary Risk Factor Intervention Project (STRIP) study, which aims to guide the study participants toward a diet beneficial for cardiovascular health. HOMA-IR was assessed annually between 15 and 20 years of age (n=518; intervention, n=245; control, n=273), along with diet, BMI, pubertal status, serum cotinine concentrations, and physical activity. Dietary counseling was given biannually during the follow-up. RESULTS HOMA-IR was lower (7.5% on average) in the intervention group than in the control group between 15 and 20 years of age (P=0.0051). The intervention effect was similar in girls and boys. The PUFA+MUFA-to-SFA ratio was higher (P<0.0001) and the dietary fiber (g/MJ) intake was higher (P=0.0058) in the intervention group compared with the control group. There was no association between the PUFA+MUFA-to-/SFA ratio and HOMA-IR, whereas dietary fiber intake (g/MJ) was associated with HOMA-IR in girls (P<0.0001). CONCLUSIONS Dietary counseling initiated in infancy and maintained until 20 years of age was associated with improved insulin sensitivity in adolescents.
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Mudaliar S. Choice of early treatment regimen and impact on β-cell preservation in type 2 diabetes. Int J Clin Pract 2013; 67:876-87. [PMID: 23952467 DOI: 10.1111/ijcp.12154] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2012] [Accepted: 02/15/2013] [Indexed: 12/21/2022] Open
Abstract
The progressive deterioration of glycaemic control in individuals with type 2 diabetes mellitus (T2DM) results from insulin resistance combined with the ongoing loss of β-cell function. Although it had been suggested that most β-cell dysfunction occurs after the development of T2DM, studies have documented a substantial early loss of β-cell function, particularly during the prediabetic state. In patients diagnosed with T2DM, β-cell function continues to decline despite treatment with commonly prescribed antihyperglycaemic medications, and ultimately exogenous insulin administration is required to maintain optimal glycaemic control. Thus, interventions to address the early decline in β-cell function could potentially alter the course of T2DM, preventing or delaying its onset and decreasing the incidence of complications. Original research and review articles on this topic were identified in a PubMed search from January 2000 through August 2012. Data from prospective studies and clinical trials suggest that lifestyle modifications and certain antihyperglycaemic medications, including thiazolidinediones (TZDs), glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors and insulin, may preserve or enhance β-cell function. The implication of current data is that early initiation of lifestyle modifications and antihyperglycaemic agents that preserve β-cell function might reverse or delay progression to T2DM in those with prediabetes. Moreover, improved β-cell function may confer more durable glucose control and perhaps reduce/delay the incidence of diabetic complications. Long-term studies are needed to validate this hypothesis.
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Affiliation(s)
- S Mudaliar
- Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA, USA.
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Houck PD, de Oliveira JMF. Applying laws of biology to diabetes with emphasis on metabolic syndrome. Med Hypotheses 2013; 80:637-42. [DOI: 10.1016/j.mehy.2012.11.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2012] [Revised: 09/09/2012] [Accepted: 11/14/2012] [Indexed: 10/27/2022]
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Abstract
The International Diabetes Federation estimates that there are currently 336 million people worldwide who have type 2 diabetes (T2DM), and the global prevalence of diabetes has more than doubled since 1980. The rapid rise in rates of T2DM echoes a similar rise in rates of obesity, which causes insulin resistance and places an increased insulin secretory demand on pancreatic β cells. While diabetes is diagnosed clinically by elevated plasma glucose levels, loss of β-cell function is progressive over time and β-cell dysfunction is far advanced by the time diabetes is diagnosed. Methods for preserving or restoring β-cell function are important for the prevention and treatment of T2DM. Interventions that reduce body fat or that change fat biology provide the best evidence for slowing or arresting the deterioration of β-cell function that causes T2DM. These interventions should form the basis of interventions to prevent and treat T2DM, particularly early in its course.
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Affiliation(s)
- Kathleen A. Page
- Division of Endocrinology and Diabetes, Department of Internal Medicine, Keck School of Medicine, University of Southern California, 1333 San Pablo Street; BMT-B11, Los Angeles, CA 90033, USA
| | - Tamar Reisman
- Department of Internal Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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Mohan V, Amutha A, Ranjani H, Unnikrishnan R, Datta M, Anjana RM, Staimez L, Ali MK, Narayan KMV. Associations of β-cell function and insulin resistance with youth-onset type 2 diabetes and prediabetes among Asian Indians. Diabetes Technol Ther 2013; 15:315-22. [PMID: 23484483 DOI: 10.1089/dia.2012.0259] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
AIM This study examined β-cell function and insulin resistance (homeostasis model assessment-insulin resistance [HOMA-IR]) in Asian Indian youth with type 2 diabetes mellitus (T2DM-Y) and prediabetes. SUBJECTS AND METHODS Eighty-two subjects with non-insulin-requiring type 2 diabetes and age of onset below 25 years were recruited within 18 months of diagnosis and compared with age- and sex-matched subjects with prediabetes (n=31) and normal glucose tolerance (NGT) (n = 83). Body mass index (BMI) and waist circumference were measured, and blood samples were taken in the fasting state and after 30, 60, 90, and 120 min of an oral glucose load for assessment of plasma glucose and insulin levels. Insulin sensitivity/resistance measures was calculated by using the reciprocal of the fasting insulin, the HOMA-IR equation, and the composite whole body insulin sensitivity index (Matsuda Index), and β-cell function was calculated by the oral disposition index (DIo). RESULTS T2DM-Y and prediabetes subjects had higher BMI, waist circumference, and fasting insulin than NGT subjects (P<0.05 for each). The 30-min insulin levels were lower in T2DM-Y and higher in prediabetes subjects compared with NGT (57 and 140 vs. 129 μIU/mL, P<0.001). The T2DM-Y group had greater insulin resistance (HOMA-IR, 1.87 vs. 0.97; P<0.05) and lower β-cell function (DIo, 0.36 vs. 3.28; P<0.001) than NGT. In separate models, the Matsuda Index and DIo were independently associated with prediabetes and T2DM-Y (P<0.05). However, when both were included together, only DIo remained associated with T2DM-Y, whereas both DIo and Matsuda Index were associated with prediabetes (P<0.05). When controlled for adiposity (BMI and waist circumference), an association was observed but in opposite directions, with waist being positively associated with prediabetes (P = 0.016) and BMI negatively associated with T2DM-Y (P = 0.009). CONCLUSIONS Among Asian Indians, β-cell dysfunction appears to be more strongly associated with T2DM-Y than insulin resistance.
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Affiliation(s)
- Viswanathan Mohan
- Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control and IDF Centre for Education, Gopalapuram, Chennai, India.
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Jermendy G. Vascular memory: can we broaden the concept of the metabolic memory? Cardiovasc Diabetol 2012; 11:44. [PMID: 22545680 PMCID: PMC3395581 DOI: 10.1186/1475-2840-11-44] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2012] [Accepted: 04/30/2012] [Indexed: 01/13/2023] Open
Abstract
Based on the results of recent randomized, controlled clinical trials and analyses of their follow-up periods the concept of metabolic memory cannot be restricted to antihyperglycaemic treatment only, rather it can be extended to lipid-lowering and antihypertensive treatment and even life-style modification. This broadened concept can be designated as vascular memory. According to this new concept, not only immediate and short-term but long-term effects of the metabolic and cardiovascular risk milieu are of great importance. Consequently, early and intensive lifestyle interventions, treatment of hyperglycaemia, lipid abnormalities and hypertension can result in beneficial effects on cardiovascular outcomes even in the long run. On the contrary, failing in target-oriented treatment from early detection of abnormalities can be associated with life-threatening cardiovascular events subsequently. Additional experimental studies are needed to characterize the exact pathomechanism of vascular memory and further clinical trials are also essential to explore its real clinical significance.
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Affiliation(s)
- György Jermendy
- Teaching Department of Internal Medicine, Bajcsy-Zsilinszky Hospital, Maglódi út, 89-91, 1106, Budapest, Hungary
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Hovatta I, de Mello VDF, Kananen L, Lindström J, Eriksson JG, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Peltonen M, Tuomilehto J, Uusitupa M. Leukocyte telomere length in the Finnish Diabetes Prevention Study. PLoS One 2012; 7:e34948. [PMID: 22493726 PMCID: PMC3321039 DOI: 10.1371/journal.pone.0034948] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2011] [Accepted: 03/06/2012] [Indexed: 12/29/2022] Open
Abstract
Leukocyte telomere length (TL) is considered a biomarker for biological aging. Shortened TL has been observed in many complex diseases, including type 2 diabetes (T2DM). Lifestyle intervention studies, e.g. the Diabetes Prevention Study (DPS), have shown a decrease in the incidence of T2DM by promoting healthy lifestyles in individuals with impaired glucose tolerance (IGT). Our aim was to study in the DPS the influence of the lifestyle intervention on TL. TL was measured by quantitative PCR-based method at two time points (N = 334 and 343) on average 4.5 years apart during the active intervention and post-intervention follow-up. TL inversely correlated with age. Our main finding was that TL increased in about two thirds of the individuals both in the intervention and in the control groups during follow-up; TL increased most in individuals with the shortest TL at the first measurement. TL was not associated with development of T2DM, nor did lifestyle intervention have an effect on TL. No association between insulin secretion or insulin resistance indices and TL was observed. We did not detect an association between TL and development of T2DM in the DPS participants. It could be due to all participants being overweight and having IGT at baseline, both of which have been found to be independently associated with shorter leukocyte TL in some earlier studies. TL had no substantial role in worsening of glucose tolerance in people with IGT. Our study confirms that leukocyte TL can increase with time even in obese people with impaired glucose metabolism.
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Affiliation(s)
- Iiris Hovatta
- Research Programs Unit, Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland.
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