56-OR: Degree of ß-Cell Function (ßCF) Impairment and Glycemic Alterations in Obese Youth (OY) Spanning from Normal Glucose Tolerance (NGT) to Impaired Glucose Tolerance (IGT) to Type 2 Diabetes (T2D): Does Race Matter?

Abstract

In OY it is not clear what degree of βCF impairment translates to increases in OGTT glucose area under the curve (G-AUC) commensurate with transition from NGT to IGT to T2D, and whether there are racial differences. Given the high rates of T2D in Black (BY) vs. White youth (WY), we hypothesized that βCF decline in BY is more detrimental and results in larger increases in G-AUC than in WY. Here we report the quantitative relationship between differences in clamp disposition index (DI=insulin sensitivity [IS] by a 3-hr hyperinsulinemic (80 mu/m2/min)-euglycemic clamp x 1st-phase insulin by a 2-hr hyperglycemic (225 mg/dL) clamp) and OGTT G-AUC in 152 OY. Two-way ANOVA (race x glycemic status) showed that in BY vs. WY larger decrements in DI from NGT to IGT and from NGT to T2D (all p<0.05) correspond to comparable increments in G-AUC (p=NS, Table), with no significant race interaction from IGT to T2D. Contrary to our hypothesis, loss of βCF in IGT and T2D is less detrimental in BY because a ∼2-3 fold greater impairment in βCF corresponds to a similar increase in G-AUC to that of WY. Such observations of preserved glucose regulation in BY compared with WY in the face of larger declines in βCF suggest an adaptive glucose-stimulated glucoregulatory mechanism protecting against dysglycemia consequent to insulin deficiency. Disclosure J. Kim: None. H.M. Tfayli: None. F. Bacha: Research Support; Self; AstraZeneca, Takeda Development Center Americas, Inc. N. Gebara: None. S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development (K24-HD01357, R01HD27503); National Center for Advancing Translational Sciences (UL1TR000005); National Center for Research Resources (UL1RR024153)