Metabolic clearance rate of insulin across the glucose tolerance spectrum by race and ethnicity in youth with obesity.

Abstract

Despite β-cell failure in youth with dysglycemia (i.e., impaired glucose tolerance [IGT] and type 2 diabetes), fasting insulin (FI) concentrations are elevated. Herein, we examined the following: 1) metabolic clearance rate of insulin (MCRI) in youth with obesity and normal glucose tolerance (NGT) versus those with IGT versus those with type 2 diabetes; 2) racial and ethnic differences in insulin dynamics; and 3) metabolic/adiposity correlates of MCRI. A total of 206 youth underwent assessment of fasting glucose, FI, MCRI and peripheral insulin sensitivity (PIS), first-phase insulin secretion, disposition index, body composition, and abdominal adiposity. In type 2 diabetes versus NGT, MCRI was lower (p < 0.001), and FI was higher (p < 0.001). In Black versus White youth, MCRI was lower (p < 0.001), driven by lower MCRI in youth with dysglycemia (p < 0.001) and not with NGT. MCRI correlated inversely with FI, as well as adiposity measures, and correlated directly with PIS and disposition index. Lower PIS, lower MCRI, and higher first-phase insulin secretion were characteristics of Black versus White youth with dysglycemia. Higher FI concentrations in the presence of dysglycemia despite β-cell failure could be explained by decreased MCRI. Racial and ethnic contrast in insulin dynamics differs by glycemic status and is more pronounced in dysglycemia manifested by lower MCRI and heightened first-phase insulin secretion in Black versus White youth.