(HealthDay News) — A genetic risk score based on 17 established insulin resistance variants and their effect sizes (weighted IR-GRS) is associated with insulin resistance at baseline and change in insulin resistance, but does not impact the effect of lifestyle intervention and metformin on insulin resistance, according to a study published online in Diabetes.

Marie-France Hivert, MD, from Harvard Medical School in Boston, and colleagues built a weighted IR-GRS in 2713 participants from the Diabetes Prevention Program (DPP). Associations were tested between the weighted IR-GRS and insulin sensitivity index at baseline. Change in insulin sensitivity index was assessed over 1 year of follow-up in the DPP intervention (metformin and lifestyle) and control arms.

The researchers found that a higher IR-GRS correlated with lower baseline insulin sensitivity index (P=.001 after full adjustment for age, sex, ethnicity, and waist circumference at baseline). No differential effect of treatment was seen for the correlation between IR-GRS on change in insulin sensitivity index; higher IR-GRS correlated with attenuation of the improvement in insulin sensitivity index over 1 year (P=.03 in fully-adjusted models; all treatment arms). 

Regardless of the genetic burden of insulin resistance-variants, lifestyle intervention and metformin improved insulin sensitivity index.

“Of high clinical importance, we showed that metformin and lifestyle improve insulin sensitivity independent of the [insulin resistance] genetic burden estimated based on current knowledge,” the researchers wrote.


  1. Hivert M-F, Christohi CA, Franks PW, et al; for the Diabetes Prevention Program Research Group. Lifestyle and metformin ameliorate insulin sensitivity independently of the genetic burden of established insulin resistance variants in Diabetes Prevention Program participants. Diabetes. 2015;doi;10.2337/db15-0950.