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

Abstract

Objective - Subjects with type 2 diabetes (T2DM) are at risk for vascular injury. Several vaso-active factors (VFs) (e.g. angiotensin) have been implicated. We hypothesize that adrenomedullin, a novel VF, is deranged in subjects with T2DM.

Research design & methods - Using a new immunoluminometric method, plasma mid-regional proADM (MR-proADM) was measured in four groups of Chinese subjects - healthy [H, N=100, fasting plasma glucose (FPG) <5.6 mM), impaired fasting glucose (IFG) (N=60, FPG 5.6-6.9 mM), diabetic with (DN, N=100) and without (DM, N=100) nephropathy. Resting forearm cutaneous micro-circulatory 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 [mean(SD)]. H 0.27(0.09) nM/L, IFG 0.29(0.13), DM 0.42(0.13) and DN 0.81(0.54) (DM vs. H & IFG P = 0.04 and DN vs. all P<0.01). Statistical adjustment for gender, age, BMI and blood pressure did not affect the conclusions. Multiple linear regression analysis revealed that highly sensitive C-reactive protein (β=0.11;P=0.01), insulin resistance index (β=0.20;P=0.001), LDL-cholesterol (β=0.31;P<0.001) and adiponectin (β=0.33;P<0.001) were significant predictors of plasma MR-proADM concentrations among non-diabetic 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 T2DM. This was further accentuated when nephropathy set in. MR-proADM was related to multiple metabolic factors and basal micro-circulatory perfusion. Adrenomedullin might play a role in the pathogenesis of diabetic vasculopathy.