Gender differences in renal responses to hyperglycemia and angiotensin-converting enzyme inhibition in diabetes

Background. Diabetes mellitus reduces female gender-mediated protection against progression of renal disease but the mechanisms responsible for this loss of protection are unknown. The impact of gender on the diabetic hyperfiltration state has not previously been studied. Since hyperfiltration is a factor in the development of diabetic renal disease, and is influenced by hyperglycemia and renin-angiotensin system (RAS) blockade, we examined gender differences in the renal response to hyperglycemia and angiotensin-converting enzyme (ACE) inhibition in young males and females with uncomplicated type 1 diabetes mellitus. Methods. Ten male and 12 female normoalbuminuric, normotensive, adolescents with type 1 diabetes mellitus were studied before ACE inhibition during clamped euglycemia and hyperglycemia, and then after 21 days treatment with enalapril (0.1 mg/kg daily x 1 week and then 0.1 mg/kg twice a day x 2 weeks). Results. During clamped euglycemia, males exhibited significantly higher effective renal plasma flow (ERPF) and renal blood flow (RBF) and a lower renal vascular resistance (RVR). During clamped hyperglycemia, females exhibited reductions in ERPF and RBF, and increased RVR and filtration fraction (FF). Males exhibited no significant renal hemodynamic changes during hyperglycemia. After ACE inhibition treatment, both genders exhibited significant declines in arterial pressure, but only females displayed a reduction in glomerular filtration rate (GFR) and FF. Conclusion. The renal responses to hyperglycemia and ACE inhibition appear to differ between male and female adolescents with uncomplicated type 1 diabetes mellitus. Hyperglycemia-induced changes in RVR and FF in women may account, at least in part, for the loss of gender-based protection in diabetic renal disease.