Tale of two Indians: Heterogeneity in type 2 diabetes pathophysiology
- 30 May 2019
- journal article
- research article
- Published by Wiley in Diabetes/Metabolism Research and Reviews
- Vol. 35 (8), e3192
- https://doi.org/10.1002/dmrr.3192
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.Keywords
Funding Information
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024)
- Fogarty International Center (D43TW009135)
- Burroughs Wellcome Fund (1008188)
- National Heart, Lung, and Blood Institute (HHSN268200900026C)
This publication has 36 references indexed in Scilit:
- CARRS Surveillance study: design and methods to assess burdens from multiple perspectivesBMC Public Health, 2012
- Reduced Time Points to Calculate the Composite IndexDiabetes Care, 2010
- Effects of Exenatide Plus Rosiglitazone on β-Cell Function and Insulin Sensitivity in Subjects With Type 2 Diabetes on MetforminDiabetes Care, 2010
- Oral Disposition Index Predicts the Development of Future Diabetes Above and Beyond Fasting and 2-h Glucose LevelsDiabetes Care, 2009
- Different Mechanisms for Impaired Fasting Glucose and Impaired Postprandial Glucose Tolerance in HumansDiabetes Care, 2006
- Effects of Traditional and Western Environments on Prevalence of Type 2 Diabetes in Pima Indians in Mexico and the U.S.Diabetes Care, 2006
- Combining probability from independent tests: the weighted Z‐method is superior to Fisher's approachJournal of Evolutionary Biology, 2005
- Insulin Resistance and Insulin Secretory Dysfunction as Precursors of Non-Insulin-Dependent Diabetes Mellitus: Prospective Studies of Pima IndiansNew England Journal of Medicine, 1993
- Homeostasis model assessment: insulin resistance and ?-cell function from fasting plasma glucose and insulin concentrations in manDiabetologia, 1985
- DIABETES MELLITUS IN AMERICAN (PIMA) INDIANSThe Lancet, 1971