An empirical index of insulin sensitivity from short IVGTT: validation against the minimal model and glucose clamp indices in patients with different clinical characteristics

Abstract

Minimal model analysis for insulin sensitivity has been validated against the glucose clamp and is an accepted method for estimating insulin sensitivity from IVGTT. However minimal model analysis requires a 3 h test and relevant expertise to run the mathematical model. The aim of this study was to suggest a simple predictor of minimal model analysis index using only 1 h IVGTT. We studied participants with different clinical characteristics who underwent 3 h regular (n = 336) or insulin-modified (n = 160) IVGTT, or 1 h IVGTT and euglycaemic-hyperinsulinaemic clamp (n = 247). Measures of insulin sensitivity were insulin sensitivity index estimated by minimal model analysis (S(I)) and the mean glucose infusion rate (clamp) (M). A calculated S(I) (CS(I)) predictor, CS(I) = Alpha X K(G)/(DeltaAUC(INS)/T), was suggested, based on the calculation of the rate of glucose disappearance K(G) and the suprabasal AUC of insulin concentration DeltaAUC(INS) over T = 40 min. For all the participants, alpha was assumed equal to the regression line slope between K(G)/(DeltaAUC(INS)/T) and S(I) in control participants. CS(I) and S(I) showed high correlation (R(2) = 0.68-0.96) and regression line slopes of approximately one in the majority of groups. CS(I) tended to overestimate S(I) in type 2 diabetic participants, but results were more reliable when CS(I) was computed with insulin-modified rather than regular IVGTT. CS(I) showed behaviours similar to S(I) as regards relationships with BMI, acute insulin response and sex. CS(I) showed good correlation with M (R(2) = 0.82). A short test can achieve a good approximation of minimal model analysis and clamp insulin sensitivity. The importance of a method such as CS(I) is that it allows analysis of IVGTT datasets with samples limited to 1 h.