133-OR: Insulin Dynamics across the Glucose Tolerance Spectrum in Youth with Obesity

Abstract

Despite β-cell failure in youth with dysglycemia (DYSG) (IGT + T2D), fasting insulin concentrations are elevated. Here, we examined 1) metabolic clearance rate of insulin (MCRI) in youth with normal glucose tolerance (NGT) and DYSG, 2) racial/ethnic differences in insulin dynamics and 3) physical and metabolic correlates of MCRI. In 95 Black (B) + 111 White (W) youth, age 14.4 ± 2.0 [SD] yrs., BMI 34.7 ± 6.4 kg/m2, MCRI and peripheral insulin sensitivity (PIS) were calculated from the hyperinsulinemic-euglycemic clamp, 1st-phase insulin (1stPhI) from the hyperglycemic clamp, disposition index (DI=PIS x 1stPhI), % body fat by DXA, visceral adipose tissue (VAT) by MRI. In DYSG vs NGT, MCRI was lower (261.6 ± 11.9 vs 334.1 ± 8.5 ml/m2/min, p<0.001) and fasting insulin was higher (46.9 ± 4.4 vs 32.9 ± 1.2 μU/mL, p<0.001). In B vs W youth (Image), MCRI was lower driven by DYSG. Lower PIS, lower MCRI and higher 1stPhI were characteristics of B youth with DYSG vs W with equally impaired DI. In B and W youth, positive correlates of MCRI were PIS and DI and negative correlates were fasting insulin, % body fat and VAT. In conclusion, higher fasting insulin concentrations in DYSG despite a failing β-cell could be explained by decreased MCRI. Racial/ethnic contrast in insulin dynamics differs by glycemic status and is more pronounced in DYSG manifested by lower PIS and lower MCRI in B vs W youth with no difference in β-cell function relative to insulin sensitivity. Disclosure W.Cho: None. F.Bacha: Other Relationship; Takeda Pharmaceutical Co., Ltd., AstraZeneca. H.M.Tfayli: Other Relationship; Novo Nordisk, Research Support; Sanofi, Novartis. S.Lee: None. S.Michaliszyn: None. J.Kim: None. S.A.Arslanian: Advisory Panel; Novo Nordisk, Eli Lilly and Company, Consultant; Société des Produits Nestlé SA,, Other Relationship; Eli Lilly and Company, AstraZeneca, Research Support; Novo Nordisk, Eli Lilly and Company. Funding American Diabetes Association (7-08-JF-27 to S.L.); Eunice Kennedy Shriver National Institute of Child Health and Human Development (K24HD01357, R01HD27503); National Center for Advancing Translational Sciences (UL1TR000005); National Center for Research