The relationship between adrenomedullin, metabolic factors, and vascular function in individuals with type 2 diabetes.

OBJECTIVE Subjects with type 2 diabetes are at risk for vascular injury. Several vasoactive factors (e.g., angiotensin) have been implicated. We hypothesize that adrenomedullin, a novel vascoactive factor, is deranged in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS Using a new immunoluminometric method, plasma midregional proadrenomedullin (MR-proADM) was measured in four groups of Chinese subjects: healthy (n = 100, fasting plasma glucose [FPG] <5.6 mmol/l), impaired fasting glucose (IFG) (n = 60, FPG 5.6-6.9 mmol/l), and diabetic subjects with (n = 100) and without (n = 100) nephropathy. Resting forearm cutaneous microcirculatory perfusion (RCMP) was quantified in vivo using 2-dimensional laser Doppler flowmetry. We investigated the relationship between plasma MR-proADM concentrations, multiple metabolic factors, and vascular function. RESULTS We observed a stepwise increase in MR-proADM among the groups: healthy group mean +/- SD 0.27 +/- 0.09, IFG group 0.29 +/- 0.13, diabetic group 0.42 +/- 0.13, and diabetic nephropathy group 0.81 +/- 0.54 nmol/l (diabetic vs. healthy and IFG groups, P = 0.04; and diabetic nephropathy group vs. all, P < 0.01). Statistical adjustment for sex, age, BMI, and blood pressure did not affect the conclusions. Multiple linear regression analysis revealed that highly sensitive C-reactive protein (beta = 0.11; P = 0.01), insulin resistance index (beta = 0.20; P = 0.001), LDL cholesterol (beta = 0.31; P < 0.001), and adiponectin (beta = 0.33; P < 0.001) were significant predictors of plasma MR-proADM concentrations among nondiabetic individuals. Among subjects with diabetes, plasma MR-proADM concentrations correlated significantly with RCMP (r = 0.43, P = 0.002). CONCLUSIONS Plasma MR-proADM concentration was elevated in subjects with type 2 diabetes. This was further accentuated when nephropathy set in. MR-proADM was related to multiple metabolic factors and basal microcirculatory perfusion. Adrenomedullin might play a role in the pathogenesis of diabetic vasculopathy.