Soluble intercellular adhesion molecule, vascular cell adhesion molecule, and impaired microvascular reactivity are early markers of vasculopathy in type 2 diabetic individuals without microalbuminuria

OBJECTIVE - Using von Willebrand Factor (VWF) as a marker of endothelial fu nction, previous studies have shown that the development of microalbuminuri a is associated with the onset of endothelial dysfunction in individuals wi th type 2 diabetes. We tested the hypothesis that endothelial dysfunction i s already evident in normoalbuminuric individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS - We used laser Doppler imaging scanning to mea sure vasodilation in the forearm skin in response to iontophoresis of 1% ac etylcholine (endothelium-dependent) and 1% sodium nitroprusside (endotheliu m-independent). Multiple indicators of endothelial function-soluble interce llular adhesion molecule (sVCAM), soluble vascular cell adhesion molecule ( sVCAM), vWF, and microvascular reactivity-were measured in 20 healthy contr ol subjects, 45 normoalbuminuric (urinary albumin/creatinine ratio <30 mu g /mg) individuals with type 2 diabetes, and 14 microalbuminuric (urinary alb umin/creatinine ratio between 30 and 300 mu g/mg) individuals with type 2 d iabetes. RESULTS - Serum sICAM and sVCAM levels were elevated in the normalbuminuric (305 +/- 120, 851 +/- 284 ng/ml) and microalbuminuric (300 +/- 89, 845 +/- 252 ng/ml) individuals with diabetes when compared with the healthy contro l subjects (213 +/- 58, 661 +/- 176 ng/ml) (P < 0.01), Furthermore, the mic rovascular endothelium-dependent and -independent vasodilation was reduced in the normoalbuminuric (76 +/- 44, 70 +/- 33) (percent increase in perfusi on over baseline) and microalbuminuric (74 +/- 41, 73 +/- 28) individuals w ith diabetes compared with healthy control subjects (126 +/- 67, 120 +/- 47 ) (P < 0.05). In contrast, plasma VWF was elevated only in the microalbumin uric individuals with diabetes (129 +/- 35%) compared with the normoalbumin uric individuals with diabetes (110 +/- 34) and healthy control subjects (1 11.3 +/- 39) (P < 0.05). On stepwise multivariate analysis, fasting blood g lucose was the most important contributing factor to the variation in micro vascular reactivity and sVCAM, whereas insulin resistance (by homeostasis m odel assessment) was the most important contributing factor to the variatio n in sICAM. Addition of all clinical and biochemical measures explained onl y 15-22% of the variation in sICAM, sVCAM, and microvascular reactivity. CONCLUSIONS- Multiple markers of endothelial dysfunction were evident in no rmoalbuminuric individuals with type 2 diabetes. The pathogenic process of vasculopathy in type 2 diabetes occurs early and may be operative before th e development of microalbuminuria.