IntroductionWith pre-diabetes and diabetes increasingly recognized as heterogeneous 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 oral glucose tolerance test (OGTT) and fasting measurements in comparison with gold standard methods.Research design and methodsThe hyperglycemic clamp extended with glucagon-like peptide 1 (GLP-1) infusion and intravenous glucose tolerance test (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-based and C-peptide-based indices were analyzed separately in different groups of glucose tolerance and the entire cohorts.ResultsThe highest correlation coefficients were found for area under curve (AUC) (I0-30)/AUC (G0-30), I30/G30, 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 hyperglycemic clamp. AUC (I0-120)/AUC (G0-120), BIGTT-AIR0-60-120, I30/G30, first-phase Stumvoll and AUC (I0-30)/AUC (G0-30) demonstrated the strongest association with incretin-stimulated insulin response.ConclusionsWe have identified glucose-stimulated 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.

Background and aimsWith 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 methodsThe 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.ResultsThe highest correlation coefficients were found for AUC (I0-30)/AUC (G0-30), 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 (I0-30)/AUC (G0-30), first-phase Stumvoll, AUC (I0-120)/AUC (G0-120) and BIGTT-AIR0-60-120 demonstrated the strongest association with incretin-stimulated insulin response.ConclusionWe 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.