Why are South Asians prone to type 2 diabetes? A hypothesis based on underexplored pathways

• Type of Material: Article
• Authors: Venkat KM Narayan, Emory University; Alka M Kanaya, University of California San Francisco
• Language: English
• Date: 2020-06-01
• Publisher: SPRINGER
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020, Springer-Verlag GmbH Germany, part of Springer Nature
• Final Published Version (URL): http://dx.doi.org/10.1007/s00125-020-05132-5
• Title of Journal or Parent Work: DIABETOLOGIA
• Volume: 63
• Issue: 6
• Start Page: 1103
• End Page: 1109
• Grant/Funding Information: KMVN’s research cited in this manuscript was funded in part 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). KMVN was also supported in part by the NIH/NHLBI (award number R01HL125442) and by the NIH National Institute of Diabetes And Digestive And Kidney Diseases (NIDDK; award number P30DK111024). Work by AMK is supported by grants from the NIH/NHLBI (award numbers 2R01HL093009 and 2K24HL112827) and by the NIH/NIDDK (award numbers P30DK098722 and 2P30K092924). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
• Keywords: INSULIN-RESISTANCE; BETA-CELL FUNCTION; Aetiology; Pathophysiology; Lean muscle mass; Evolutionary biology; WEIGHT; VISCERAL FAT; Endocrinology & Metabolism; SouthAsians; UNITED-STATES; INDIANS; MUSCLE; Science & Technology; Type 2 diabetes; RACIAL/ETHNIC GROUPS; Review; Hepatic fat; BODY-COMPOSITION; Insulin secretion; RISK; Life Sciences & Biomedicine

Abstract

South Asians have a high prevalence of type 2 diabetes, even at a lower BMI. This review sets out our perspective and hypothesis on the reasons for this. Emerging data from epidemiological studies indicate that South Asians may have a lower ability to secrete insulin, and thus may have less compensatory reserves when challenged with unhealthy lifestyles. Thus, insulin resistance may not be the primary driver of type 2 diabetes in this population. Furthermore, data also suggest that South Asians, on average, have lower muscle mass, and may have a specific propensity to ectopic hepatic fat accumulation and for intramyocellular fat deposition, which cause further disruption in insulin action. We hypothesise that the high diabetes susceptibility in South Asians is evolutionarily set through dual parallel and/or interacting mechanisms: reduced beta cell function and impaired insulin action owing to low lean mass, which is further accentuated by ectopic fat deposition in the liver and muscle. These areas warrant further research.