Beta-cells in youth with impaired glucose tolerance or early type 2 diabetes secrete more insulin and are more responsive than in adults

Objective: Glycemic control deteriorates more rapidly in youth vs adults. We compared model-derived measures of ?-cell function between youth and adults with either impaired glucose tolerance (IGT) or type 2 diabetes to determine if a ?-cell defect differentiates these age groups. Methods: This is a cross-sectional analysis of baseline data from the Restoring Insulin Secretion (RISE) Study. Youth (54 Y-IGT, 33 Y-D) and adults (250 A-IGT, 104 A-D) underwent 3-hour oral glucose tolerance tests for modeling of insulin secretion rates (ISRs), glucose sensitivity, and rate sensitivity. Insulin sensitivity was quantified as the glucose infusion rate/insulin (M/I) from a hyperglycemic clamp. Results: Youth had lower insulin sensitivity despite similar body mass index. Analyses were adjusted for insulin sensitivity. Youth had higher basal ISRs (Y-IGT 200 ± 161 vs A-IGT 152 ± 74, P <.001; Y-D 245 ± 2.5 vs A-D 168 ± 115 pmol/min/m2, P =.007) and total ISRs (Y-IGT 124 ± 86 vs A-IGT 98 ± 39, P <.001; Y-D 116 ± 110 vs A-D 97 ± 62 nmol/m2, P =.002). Within IGT, glucose sensitivity (Y-IGT 140 ± 153 vs A-IGT 112 ± 70 pmol/min/m2/mM, P =.004) and rate sensitivity (median[interquartile range]:Y-IGT 2271[1611, 3222] vs A-IGT 1164[685, 1565] pmol/m2/mM, P <.001) were higher in youth, but not different by age group within diabetes. Conclusions: Model-derived measures of ?-cell function provide additional insight into the pathophysiology of type 2 diabetes in youth with higher ISRs and ?-cell secretion more responsive to glucose in youth relative to adults even after adjusting for differences in insulin sensitivity. It is unknown whether these findings in youth reflect ?-cells that are healthier or whether this is a defect that contributes to more rapid loss of function