A novel surrogate index for hepatic insulin resistance

In epidemiological and genetic studies surrogate indices are needed to investigate insulin resistance in different insulin-sensitive tissues. Our objective was to develop a surrogate index for hepatic insulin resistance. A sample of 368 non-diabetic participants (age 43.0 +/- 8.2 years, BMI 26.0 +/- 4.0 kg/m(2); mean +/- SD) whose endogenous glucose production (EGP) was measured with [6-6(2)H(2)]glucose in the fasting state and during the euglycaemic-hyperinsulinaemic clamp were included in the study. EGP multiplied by fasting plasma insulin (FPI) concentration was the reference measurement for liver insulin resistance (liver IR). Liver IR index was calculated with linear regression analysis including age, obesity indices, lipids, lipoproteins and several variables regulating glucose metabolism. The following variables were significantly associated with liver IR in multiple forward stepwise regression analysis: insulin AUC in an OGTT, fat mass, HDL-cholesterol and BMI. Liver IR index correlated significantly with EGPxFPI (r = 0.65, p < 0.001). In participants with abnormal glucose tolerance, the correlation of liver IR with EGPxFPI was slightly stronger (r = 0.69, p < 0.001) than in those with normal glucose tolerance (r = 0.62, p < 0.001). We generated a novel surrogate index for liver insulin resistance correlating strongly with EGP x FPI.