Insulin Clearance at the Pubertal Transition in Youth with Obesity and Steatosis Liver Disease

Abstract

No data are available on insulin clearance (ClI) trends during the pubertal transition. The aim of this study was to investigate in 973 youths with obesity whether ClI in fasting and post-oral glucose challenge (OGTT) conditions varies at the pubertal transition in relation to the severity of obesity and the presence of steatosis liver disease (SLD). The severity of obesity was graded according to the Centers for Disease Control. SLD was graded as absent, mild and severe based on alanine amino transferase levels. ClI was defined as the molar ratio of fasting C-peptide to insulin and of the areas under the insulin to glucose curves during an OGTT. In total, 35% of participants were prepubertal, 72.6% had obesity class II, and 52.6% had mild SLD. Fasting ClI (nmol/pmol × 10−2) was significantly lower in pubertal [0.11 (0.08–0.14)] than in prepubertal individuals [0.12 (0.09–0.16)] and higher in class III [0.15 (0.11–0.16)] than in class I obesity [0.11 (0.09–0.14)]. OGTT ClI was higher in boys [0.08 (0.06–0.10)] than in girls [0.07 (0.06–0.09)]; in prepubertal [0.08 (0.06–0.11)] than in pubertal individuals [0.07 (0.05–0.09)]; in class III [0.14 (0.08–0.17)] than in class I obesity [0.07 (0.05–0.10)]; and in severe SLD [0.09 (0.04–0.14)] than in no steatosis [0.06 (0.04–0.17)]. It was lower in participants with prediabetes [0.06 (0.04–0.07)]. OGTT ClI was lower in youths with obesity at puberty along with insulin sensitivity and greater secretion. The findings suggest that the initial increase in ClI in youth with severe obesity and SLD is likely to compensate for hyperinsulinemia and its subsequent decrease at the onset of prediabetes and other metabolic abnormalities.