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

Aims/hypothesis: 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. Methods: 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 (SI) and the mean glucose infusion rate (clamp) (M). A calculated SI (CSI) predictor, CSI = α × KG}/(Δ AUCINS/T) was suggested, based on the calculation of the rate of glucose disappearance K G and the suprabasal AUC of insulin concentration ΔAUCINS over T=40 min. For all the participants, α was assumed equal to the regression line slope between K G/(ΔAUCINS/T) and SI in control participants. Results: CSI and SI showed high correlation (R 2=0.68-0.96) and regression line slopes of approximately one in the majority of groups. CSI tended to overestimate SI in type 2 diabetic participants, but results were more reliable when CSI was computed with insulin-modified rather than regular IVGTT. CSI showed behaviours similar to SI as regards relationships with BMI, acute insulin response and sex. CSI showed good correlation with M (R 2=0.82). Conclusions/ interpretation: A short test can achieve a good approximation of minimal model analysis and clamp insulin sensitivity. The importance of a method such as CSI is that it allows analysis of IVGTT datasets with samples limited to 1 h.