CHEE FANG SUM, MBBS1 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 glucose (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.
Diabetes Care 30:1513-1519, 2007I ndividuals with type 2 diabetes are at risk for vascular injury. Although major advances have been made in uncovering the mechanism of diabetic vasculopathy, the exact pathophysiology remains incompletely understood (1). In recent years, the importance of endothelial dysfunction has taken central stage (2). By secreting a repertoire of finely regulated vasoactive factors with opposing functions working in autocrine and paracrine fashion, the endothelium is pivotal in maintaining vascular homeostasis (3). Numerous vascoactive factors have been described. Among these factors, adrenomedullin, a 52-amino acid peptide, has been intensively investigated due to its vascular protective properties (e.g., vasodilatory and antiproliferative) and promising potential as a therapeutic target (4). However, understanding of the pathobiology of adrenomedullin in diabetic vasculopathy has only just begun.In healthy states, adrenomedullin circulates at low picomolar concentration, which i...