Endothelial function in offspring of Type 1 diabetic patients with and without diabetic nephropathy.
OBJECTIVE
Familial aggregation of diabetes and nephropathy has been observed in several populations. Various interpretations have included underlying genetic mechanisms possibly mediated by a predisposition to hypertension. Endothelial dysfunction is now recognized as central to these conditions and offers a unifying mechanism to explain the disease aggregation. To test this hypothesis, we have examined endothelial function in healthy subjects at differing risks for diabetic nephropathy.


METHODS
Endothelial function was assessed in 12 healthy offspring (nine male (M)/three female (F); age 25.8+/-1.2 years, mean +/- SEM) of parents with Type 1 diabetes mellitus (DM) 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. Forearm blood flow responses to brachial artery infusion of acetylcholine (endothelium-dependent), sodium nitroprusside (endothelium-independent), noradrenaline and the competitive inhibitor of basal nitric oxide release N(G)-monomethyl-L-arginine were assessed using venous occlusion plethysmography.


RESULTS
There were no significant differences between the groups in von Willebrand 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 to 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).


CONCLUSIONS
These data do not support a role for endothelial dysfunction in the familial aggregation of diabetic nephropathy.
McAllister
A S
AS
Sir George E. Clark Metabolic Unit, Royal Victoria Hospital, Belfast, UK.
Atkinson
A B
AB
Johnston
G D
GD
McCance
D R
DR
D000328:Adult; D002908:Chronic Disease; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005192:Family Health; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D012016:Reference Values; D012039:Regional Blood Flow; D012307:Risk Factors