Endothelial function in offspring of Type 1 diabetic patients with and without diabetic nephropathy

Aims Familial aggregation of diabetes and nephropathy has been observed in several populations. Various interpretations have included underlying genet ic mechanisms possibly mediated by a predisposition to hypertension. Endoth elial dysfunction is now recognized as central to these conditions and offe rs a unifying mechanism to explain the disease aggregation. To test this hy pothesis, we have examined endothelial function in healthy subjects at diff ering risks for diabetic nephropathy. Methods Endothelial function was assessed in 12 healthy offspring (nine mal e (M)/three female (F); age 25.8 +/- 1.2 years, mean +/- SEM) of parents wi th Type 1 diabetes mellitus IDM) and end-stage renal disease compared with 12 control offspring (9 M/3 F; age 26.3 +/- 1.3 years) of parents with long duration (> 20 years) Type 1 DM but without evidence of nephropathy. Forea rm blood flow responses to brachial artery infusion of acetylcholine (endot helium-dependent), sodium nitroprusside (endothelium-independent), noradren aline and the competitive inhibitor of basal nitric oxide release N-G-monom ethyl-L-arginine were assessed using venous occlusion plethysmography. Results There were no significant differences between the groups in von Wil lebrand factor, fasting plasma glucose (4.2 +/- 0.1 vs. 4.0 +/- 0.2 mmol/l) or in 24-h ambulatory blood pressure. Similarly, the groups did not differ in vasodilation tu acetylcholine (P = 0.75) and sodium nitroprusside (P = 0.79) or in vasoconstriction to noradrenaline (P = 0.45) and N-G-monomethyl -L-arginine (P = 0.30). Conclusion These data do not support a role for endothelial dysfunction in the familial aggregation of diabetic nephropathy.