Tale of two Indians: Heterogeneity in type 2 diabetes pathophysiology

• Type of Material: Article
• Authors: Lisa Staimez, Emory University; M. Deepa, Madras Diabetes Research Foundation; Mohammed Ali, Emory University; Viswanathan Mohan, Madras Diabetes Research Foundation; Robert L. Hanson, National Institute of Diabetes and Digestive and Kidney Diseases; Kabayam Venkat Narayan, Emory University
• Language: English
• Date: 2019-07-29
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 John Wiley & Sons, Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1002/dmrr.3192
• Title of Journal or Parent Work: DIABETES-METABOLISM RESEARCH AND REVIEWS
• Volume: 35
• Issue: 8
• Start Page: e3192
• End Page: e3192
• Grant/Funding Information: The CARRS Study was supported by the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Department of Health and Human Services, under Contract No. HHSN268200900026C, and the United Health Group, Minneapolis, MN, USA. LRS was supported by the Molecules to Mankind Program sponsored by the Burroughs Wellcome Fund (BWF Award Number 1008188). MD was supported in part by the Fogarty International Center of the NIH under Award Number D43TW009135. MKA was supported by NHLBI Contract No. HHSN268200900026C; the United Health Group, Minneapolis, MN, USA; and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH, Award Number P30DK111024. The sponsors had no role in the design and conduct of the study; management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. RLH was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. KMVN was supported in part by NIDDK Award Number P30DK111024. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Parts of this study were presented at the 74th Scientific Sessions of the American Diabetes Association, San Francisco, CA, June 13-17, 2014.
• Keywords: pathophysiology; POPULATION; INSULIN-RESISTANCE; NORMAL-WEIGHT; INDIVIDUALS; insulin resistance; epidemiology; Science & Technology; ethnicity; PIMA-INDIANS; BETA-CELL FUNCTION; insulin secretion; type 2 diabetes; PREVALENCE; RACIAL/ETHNIC GROUPS; IMPAIRED FASTING GLUCOSE; RISK; Endocrinology & Metabolism; Life Sciences & Biomedicine

Abstract

Aims: Type 2 diabetes is a heterogeneous disease and may manifest from multiple disease pathways. We examined insulin secretion and insulin resistance across two ethnicities with particularly high risk for diabetes yet with widely different distributions of weight class. Materials and Methods: In this population-based, cross-sectional study, Pima Indians from Southwestern United States (n = 865) and Asian Indians from Chennai, India (n = 2374) had a 75-g oral glucose tolerance test. We analysed differences in plasma glucose, plasma insulin, insulin resistance (HOMA-IR), and insulin secretion (ΔI0-30/ΔG0-30) across categories of body mass index (BMI) and glycemic status per American Diabetes Association criteria. Results: Pima Indians were younger (mean 27.4 ± SD 6.6, Asian: 33.9 ± 6.7 years) and had higher BMI (33.6 ± 8.1, Asian: 25.7 ± 4.9 kg/m2). Among normal weight participants (mean BMI: Pima 22.4 SE 0.2; Asian 22.2 SE 0.06 kg/m2), fasting glucose was higher in Asian Indians (5.2 vs Pima: 4.8 mmol/L, P =.003), adjusted for age and sex. Pima Indians were three times as insulin resistant as Asian Indians (HOMA-IR: 7.7 SE 0.1, Asian: 2.5 SE 0.07), while Asian Indians had three times less insulin secretion (Pima: 2.8 SE 1.0 vs Asian: 0.9 SE 1.0 pmol/mmol), a pattern evident across age, BMI, and glycemic strata. Conclusions: Metabolic differences between Pima and Asian Indians suggest heterogeneous pathways of type 2 diabetes in the early natural history of disease, with emphasis of insulin resistance in Pima Indians and emphasis of poor insulin secretion in Asian Indians.