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The Relationship Between Adrenomedullin, Metabolic Factors, and Vascular Function in Individuals With Type 2 Diabetes

¹ Department of Medicine, Alexandra Hospital, Singapore, Republic of Singapore
² Research Department, B.R.A.H.M.S. AG Biotechnology Center, Hennigsdorf/Berlin, Germany

Address correspondence and reprint requests to Su Chi Lim, Department of Medicine, Alexandra Hospital, 378 Alexandra Rd., Singapore 159964, Republic of Singapore. E-mail: su_chi_lim{at}alexhosp.com.sg

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 (ß = 0.11; P = 0.01), insulin resistance index (ß = 0.20; P = 0.001), LDL cholesterol (ß = 0.31; P < 0.001), and adiponectin (ß = 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.

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

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