Insulin Resistance in Congenital Adrenal Hyperplasia is Compensated for by Reduced Insulin Clearance.
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/m2 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 ~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.
['de Oliveira|Daniel Minutti|DM|', 'Tura|Andrea|A|', 'Vasques|Ana Carolina Junqueira|ACJ|', 'Camilo|Daniella Fernandes|DF|', 'Lima|Marcelo Miranda|MM|', 'de Lemos-Marini|Sofia Helena Valente|SHV|', 'Goncalves|Ezequiel Moreira|EM|', 'Guerra-Junior|Gil|G|', 'Geloneze|Bruno|B|']
D000312:Adrenal Hyperplasia, Congenital D000328:Adult D003430:Cross-Sectional Studies D005260:Female D006801:Humans D006946:Hyperinsulinism D007328:Insulin D007333:Insulin Resistance D050417:Insulin-Secreting Cells D008297:Male D055815:Young Adult
insulin resistance congenital adrenal hyperplasia hepatic insulin clearance beta cell corticoesteroids obesity