Insulin Resistance in Congenital Adrenal Hyperplasia is Compensated for by Reduced Insulin Clearance

Author(s)

de Oliveira, Daniel Minutti ^[1] ; Tura, Andrea ^[2] ; Junqueira Vasques, Ana Carolina ^{[1, 3]} ; Camilo, Daniella Fernandes ^[1] ; Lima, Marcelo Miranda ^[1] ; Valente de Lemos-Marini, Sofia Helena ^[4] ; Goncalves, Ezequiel Moreira ^[5] ; Guerra-Junior, Gil ^{[4, 5]} ; Geloneze, Bruno ^{[1, 6]}

Affiliation

^[1] Univ Estadual Campinas, Gastroctr, Lab Invest Metab & Diabet LIMED, UNICAMP, Rua Carlos Chagas, 420 Cidade Univ, BR-13083878 Campinas, SP - Brazil

^[2] CNR, Metab Unit, Inst Neurosci, Padua - Italy

^[3] Univ Estadual Campinas, Sch Appl Sci, UNICAMP, Limeira - Brazil

^[4] Univ Estadual Campinas, Pediat Endocrinol Dept, UNICAMP, Campinas - Brazil

^[5] Univ Estadual Campinas, Growth & Dev Lab, Ctr Invest Pediat CIPED, UNICAMP, Campinas - Brazil

^[6] Univ Estadual Campinas, Obes & Comorb Res Ctr OCRC, UNICAMP, Campinas - Brazil

• Document type: Journal article
• Source: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 106, n. 4, p. E1574-E1585, APR 2021.
• Web of Science Citations: 0

Abstract

Context: Congenital adrenal hyperplasia (CAH) patients have potential normal longevity. However, a greater risk for cardiovascular disease has been reported. Insulin resistance and hyperinsulinemia have been described in CAH patients, whereas the prevalence of overt type 2 diabetes is not higher in CAH than in normal population. Objective: To examine the contributions of insulin secretion and of hepatic insulin clearance to compensatory hyperinsulinemia in young insulin-resistant adults with classic CAH due to 21-hydroxylase deficiency (21-OHD). Design: Cross-sectional. Setting: University outpatient clinics. Methods: Fifty-one participants: 21 controls, and 30 CAH (15 virilizing and 15 salt-wasting phenotypes), female/male (33/18), age (mean {[}SD]): 24.0 (3.6) years, body mass index: 24.6 (4.9)kg/m(2) with normal glucose tolerance, were submitted to a hyperglycemic clamp study. Main outcome measures: Insulin sensitivity, beta cell function, and hepatic insulin clearance using appropriate modeling. Results: We found an increased insulin resistance in 21-OHD. The systemic hyperinsulinemia (posthepatic insulin delivery) was elevated in CAH patients. No increases were observed in insulin secretory rate (beta cell function) in the first phase or during the hyperglycemic clamp. The increase in insulin concentrations was totally due to a similar to 33% reduction in insulin clearance. Conclusion: 21-OHD nonobese subjects have reduced insulin sensitivity and beta cell response unable to compensate for the insulin resistance, probably due to overexposure to glucocorticoids. Compensatory hyperinsulinemia is most related with reduced hepatic insulin clearance. The exclusive adaptation of the liver acts as a gating mechanism to regulate the access of insulin to insulin-sensitive tissues to maintain glucose homeostasis. (AU)

• FAPESP's process: 12/16778-8 - Cardiometabolic evaluation and pancreatic beta cell secretion pattern in congenital adrenal hyperplasia patients
• Grantee: Gil Guerra Júnior
• Support type: Regular Research Grants
• FAPESP's process: 11/23460-1 - Cardiometabolic risk in patients with classical Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency.
• Grantee: Ezequiel Moreira Gonçalves
• Support type: Scholarships in Brazil - Post-Doctorate