Adiposity and family history of type 2 diabetes in an admixed population of adolescents: Associations with insulin sensitivity, beta-cell function, and hepatic insulin extraction in BRAMS study

Aims: Insulin resistance and beta-cell dysfunction manifest differently across racial/ethnic groups, and there is a lack of knowledge regarding the pathophysiology of type 2 diabetes mellitus (T2DM) for ethnically admixed adolescents. This study aimed to investigate the influence of adiposity and family history (FH) of T2DM on aspects of insulin sensitivity, beta-cell function, and hepatic insulin extraction in Brazilian adolescents. Methods: A total of 82 normoglycemic adolescents were assessed. The positive FH of T2DM was defined as the presence of at least one known family member with T2DM. The hyperglycemic clamp test consisted of a 120-min protocol. Insulin secretion and beta-cell function were obtained from C-peptide deconvolution. Analysis of covariance considered pubertal stage as a covariate. Results: Both lean and overweight/obese adolescents had similar glycemic profiles and disposition indexes. Overweight/obese adolescents had about 1/3 the insulin sensitivity of lean adolescents (1.1 ± 0.2 vs. 3.4 ± 0.3 mg·kg·min·pmol * 1000), which was compensated by an increase around 2.5 times in basal (130 ± 7 vs. 52 ± 10 pmol·l·min) and total insulin secretion (130,091 ± 12,230 vs. 59,010 ± 17,522 pmol·l·min), and in the first and second phases of insulin secretion; respectively (p < 0.001). This increase was accompanied by a mean reduction in hepatic insulin extraction of 35%, and a 2.7-time increase in beta-cell glucose sensitivity (p < 0.05). The positive FH of T2DM was not associated with derangements in insulin sensitivity, beta-cell function, and hepatic insulin extraction. Conclusions: In an admixed sample of adolescents, the hyperglycemic clamp test demonstrated that adiposity had a strong influence, and FH of T2DM had no direct influence, in different aspects of glucose metabolism.