Asian Indian Prediabetes Study

Summary

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Compared to other races, Indians have a greater risk of developing type 2 diabetes (T2D), increased insulin resistance (IR) and more rapid decline in ?-cell function, highlighting the urgency and importance of early intervention strategies for improving insulin sensitivity and preserving/improving ?...

Compared to other races, Indians have a greater risk of developing type 2 diabetes (T2D), increased insulin resistance (IR) and more rapid decline in ?-cell function, highlighting the urgency and importance of early intervention strategies for improving insulin sensitivity and preserving/improving ?-cell function to prevent T2D and mitigate against the increased vascular disease risk. Preliminary findings show a reduction in glycemic load selectively depletes visceral and ectopic lipid and improves insulin sensitivity and ?-cell function in non-diabetic adults. The proposed research will investigate if the phenotypic features increasing T2D risk in individuals of Indian ancestry (IR and impaired ?-cell function) can be favorably modified by a low glycemic (LG) intervention, and if the increased IR is attributable to genetic factors regulating adipocyte differentiation and function. These research objectives will be achieved through a 24-week randomized controlled trial (RCT) comparing isocaloric LG versus control diets in Indians with prediabetes. Compared to individuals in the control group, those on the LG diet are expected to have greater ectopic (pancreas, liver, visceral and intramyocellular) fat depletion assessed with MRI/MRS, and improvements in first phase insulin secretion and insulin sensitivity assessed with the C-peptide model and oral minimal model, respectively during an OGTT. Reductions in hepatic and pancreatic lipids will be associated with improvements in first-phase ?-cell response. Individuals with a greater number of risk alleles from a 53-SNP IR genetic risk score will have lower insulin sensitivity and leg fat, supporting the notion that impaired adipocyte differentiation leading to limited peripheral adipose expansion capacity is an important etiological factor underpinning IR cardiometabolic disease in Indians. The results will broaden the evidence base for effective prevention strategies in this high risk population by investigating the effect of the proposed diet intervention on underlying physiological and molecular mechanisms implicated in the pathophysiology of T2D in Indians.

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