Comprehensive validation of fasting- and oral glucose tolerance test-based indices of insulin secretion against gold-standard measures

Background and aims With prediabetes and diabetes increasingly recognized as heterogenous conditions, assessment of beta-cell function is gaining clinical importance to identify disease subphenotypes. Our study aims to comprehensively validate all types of surrogate indices based on OGTT- and fasting-measurements in comparison with gold standard methods. Materials and methods The hyperglycaemic clamp extended with GLP-1 infusion and IVGTT, as well as OGTT, was performed in two well-phenotyped cohorts. The gold-standard-derived indices were compared with surrogate insulin secretion markers, derived from fasting state and OGTT, using both Pearson’s and Spearman’s correlation coefficients. The insulin- and C-peptide-based indices were analysed separately in different groups of glucose tolerance and the entire cohorts. Results The highest correlation coefficients were found for AUC (I 0-30 )/AUC (G 0-30 ), first-phase Stumvoll and Kadowaki model. These indices have high correlation coefficients with measures obtained from both insulin and C-peptide levels from IVGTT and hyperglycaemic clamp. AUC (I 0-30 )/AUC (G 0-30 ), first-phase Stumvoll, AUC (I 0-120 )/AUC (G 0-120 ) and BIGTT-AIR 0-60-120 demonstrated the strongest association with incretin-stimulated insulin response. Conclusion We have identified glucose- and GLP-1-stimulated insulin secretion indices, derived from OGTT and fasting state, that have the strongest correlation with gold-standard measures and could be potentially used in future researches and clinical practice.