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 ϭ 100, fasting plasma glucose [FPG] Ͻ5.6 mmol/l), impaired fasting

more »

... cose (IFG) (n ϭ 60, FPG 5.6 -6.9 mmol/l), and diabetic subjects with (n ϭ 100) and without (n ϭ 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 Ϯ SD 0.27 Ϯ 0.09, IFG group 0.29 Ϯ 0.13, diabetic group 0.42 Ϯ 0.13, and diabetic nephropathy group 0.81 Ϯ 0.54 nmol/l (diabetic vs. healthy and IFG groups, P ϭ 0.04; and diabetic nephropathy group vs. all, P Ͻ 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 (␤ ϭ 0.11; P ϭ 0.01), insulin resistance index (␤ ϭ 0.20; P ϭ 0.001), LDL cholesterol (␤ ϭ 0.31; P Ͻ 0.001), and adiponectin (␤ ϭ 0.33; P Ͻ 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 ϭ 0.43, P ϭ 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. Abbreviations: ACR, albumin-to-creatinine ratio; hsCRP, highly sensitive C-reactive protein; FPG, fasting plasma glucose; GLM, general linear model; HOMA-IR, homeostasis model assessment of insulin resistance; IFG, impaired fasting glucose; MR-proADM, midregional proadrenomedullin; RCMP, resting forearm cutaneous microcirculatory perfusion. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.