Interaction between uric acid and endothelial dysfunction predicts new onset of diabetes in hypertensive patients

Both uric acid and endothelial dysfunction are associated with new occurrence of type-2 diabetes but, at this moment, there is no evidence about a possible interaction between them. We tested, in untreated hypertensive patients, without clinical evidence of vascular damage, the hypothesis that serum uric acid and endothelial dysfunction may interact in predicting new diabetes.

In 500 uncomplicated hypertensive non diabetic (ADA criteria) patients we evaluated endothelial function, by strain-gauge plethysmography, and uric acid.

During the follow-up (median 87.1 months), there were 54 new cases of diabetes (1.8%/year). On univariate analysis, incident diabetes was inversely related with ACh-stimulated FBF (HR=0.65, 95%CI=0.52-0.82; P<0.001) and directly with serum CRP (HR=1.22, 95%CI=1.09-1.37; P<0.001), HOMA-index (HR=1.20, 95%CI=1.05-1.37; P=0.007), fasting insulin (HR=1.05, 95%CI=1.01-1.09; P=0.006) and age (HR=1.03, 95%CI=1.00-1.05; P=0.014). At multiple regression analysis, the interaction between ACh-stimulated FBF and uric acid resulted statistically significant. Similar results were observed for the interaction between FBF and CRP.

Our data clearly demonstrate that the coexistence of both hyperuricemia and reduced endothelium-dependent vasodilation increases the risk to develop new diabetes in hypertensive patients. In addition, mild-inflammation seems to be the mediator of the interaction between endothelial dysfunction and uric acid.