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

• Published in: Diabetes care Vol. 30; no. 6; pp. 1513 - 1519
• Main Authors: Lim, Su Chi, Morgenthaler, Nils G, Subramaniam, Tavintharan, Wu, Yew Seng, Goh, Siew Kheng, Sum, Chee Fang
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.06.2007
• Subjects: adiponectin; Adrenomedullin; Adrenomedullin - blood; Adult; Associated diseases and complications; Biological and medical sciences; blood; Blood circulation disorders; blood glucose; Blood Pressure; Blood Vessels; Blood Vessels - physiopathology; Body Mass Index; C-reactive protein; Circulatory system; Complications and side effects; Diabetes; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic Angiopathies; Diabetic Angiopathies - blood; Diabetic Angiopathies - physiopathology; Diabetic Nephropathies; Diabetic Nephropathies - blood; Diabetic Nephropathies - physiopathology; diabetic nephropathy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; fasting; Female; glucose; Glucose Intolerance; Glucose Intolerance - blood; Glucose Intolerance - physiopathology; Hormones; Humans; Hyperglycemia; insulin resistance; Kidney diseases; Kidneys; linear models; low density lipoprotein cholesterol; Male; Medical sciences; Metabolism; Middle Aged; Miscellaneous; Nephrology. Urinary tract diseases; noninsulin-dependent diabetes mellitus; pathogenesis; physiopathology; Protein Precursors; Protein Precursors - blood; Proteins; Public health. Hygiene; Public health. Hygiene-occupational medicine; Reference Values; regression analysis; risk; Risk factors; Studies; Type 2 diabetes; Urinary system involvement in other diseases. Miscellaneous; United States; Endocrinopathy; Kidney disease; Type 2 diabetes; Human; Urinary system disease; Pathogenesis; Diabetes mellitus; Adrenomedullin; Metabolic diseases; Concomitant disease; Nephropathy; Blood vessel; Diabetic nephropathy; Circulatory system
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc06-1899

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 (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 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.