de Oliveira DM, Tura A, Vasques ACJ, et al. - Researchers conducted this cross-sectional study to explore the contributions of insulin secretion and of hepatic insulin clearance to compensatory hyperinsulinemia in young insulin resistant adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). Fifty-one candidates were submitted to a hyperglycemic clamp study: 21 controls, and 30 CAH (15 virilizing and 15 salt-wasting phenotypes), female/male (33/18), age [mean (SD)]: 24.0 (3.6) years, BMI: 24.6 (4.9) kg/m² with normal glucose tolerance. According to findings, 21-OHD non-obese individuals have decreased insulin sensitivity, and beta-cell response unable to compensate for the insulin resistance, likely due to glucocorticoid overexposure. Compensatory hyperinsulinemia is often associated with lower hepatic insulin clearance. In order to maintain glucose homeostasis, the exclusive adaptation of the liver serves as a gating mechanism to regulate insulin access to insulin-sensitive tissues.