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Endothelial function in offspring of Type 1 diabetic patients with and without diabetic nephropathy
A S McAllister1, A B Atkinson, G D Johnston
1Sir George E. Clark Metabolic Unit, Royal Victoria Hospital, Belfast, UK.
Insights
Endothelial dysfunction does not appear to play a role in the familial aggregation of diabetic nephropathy. This study found no significant differences in endothelial function between healthy individuals with a high risk and those with a low risk for diabetic kidney disease.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Genetics
Background:
- Familial aggregation of diabetes and nephropathy suggests shared genetic or environmental factors.
- Endothelial dysfunction is a potential unifying mechanism for these conditions.
- Understanding familial aggregation is key to identifying predisposition to diabetic nephropathy.
Purpose of the Study:
- To investigate the role of endothelial dysfunction in the familial aggregation of diabetic nephropathy.
- To compare endothelial function in healthy individuals with differing risks for diabetic nephropathy.
Main Methods:
- Assessed endothelial function in two groups of healthy offspring: those with parents who had Type 1 diabetes mellitus (DM) and end-stage renal disease, and controls with parents who had Type 1 DM but no nephropathy.
- Measured forearm blood flow responses to various infusions, including acetylcholine and sodium nitroprusside, using venous occlusion plethysmography.
Main Results:
- No significant differences were observed between the groups in markers of endothelial function, including vasodilation and vasoconstriction responses.
- Fasting plasma glucose, 24-h ambulatory blood pressure, and von Willebrand factor levels were similar in both groups.
Conclusions:
- The findings do not support a role for endothelial dysfunction in the familial aggregation of diabetic nephropathy.
- Further research may be needed to explore other potential mechanisms underlying the familial clustering of diabetes and kidney disease.
Aims:
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).
Conclusion:
These data do not support a role for endothelial dysfunction in the familial aggregation of diabetic nephropathy.