Predictability of genetic risk score for insulin resistance is influenced by both BMI and race

Abstract

Objective

The study objective was to determine whether associations between a genetic risk score (GRS) for insulin resistance (IR) and measures of insulin sensitivity differ by race and/or BMI status in African American (AA) and European American (EA) adults without diabetes.

Methods

Fifty-three AA and 54 EA participants were classified into “high” or “low” BMI groups using the sample median (25.9 kg/m²) as the cut point. The GRS was derived from 52 previously identified genetic variants. Skeletal muscle insulin sensitivity was measured with the hyperinsulinemic-euglycemic clamp. The homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index of insulin sensitivity were calculated from oral glucose tolerance test values to determine hepatic and whole-body insulin sensitivity, respectively. Linear regression models, stratified by race, assessed interactions between BMI status and GRS on measures of insulin sensitivity.

Results

In EA participants, associations of GRS with HOMA-IR and the Matsuda index differed by BMI status, where the GRS was associated with IR in the high-BMI group only. In AA participants, associations from the clamp differed by BMI status, but an association was observed only in the low-BMI group.

Conclusions

These results highlight the heterogeneity of IR and support the hypothesis that the relationship between genetic predisposition for IR and obesity is race- and tissue-specific.