Endothelial Markers May Link Kidney Function to Cardiovascular Events in Type 2 Diabetes

• Published in: Diabetes care Vol. 32; no. 10; pp. 1890 - 1895
• Main Authors: Maier, Christina, Clodi, Martin, Neuhold, Stephanie, Resl, Michael, Elhenicky, Marie, Prager, Rudolf, Moertl, Deddo, Strunk, Guido, Luger, Anton, Struck, Joachim, Pacher, Richard, Hülsmann, Martin
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.10.2009
• Subjects: Adrenomedullin - metabolism; Atrial Natriuretic Factor - metabolism; Biological and medical sciences; Cardiac patients; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - etiology; Cardiovascular Diseases - metabolism; Cholesterol; Creatinine - blood; Development and progression; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Diabetics; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelin-1 - metabolism; Endothelium; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glycopeptides - metabolism; Heart attacks; Hospitalization; Hospitals; Humans; Hyperglycemia; Kidney - metabolism; Kidney - pathology; Male; Medical research; Medical sciences; Medicine, Experimental; Metabolic diseases; Metabolic syndrome; Middle Aged; Miscellaneous; Natriuretic peptides; Original Research; Pituitary hormones; Plasma; Proportional Hazards Models; Prospective Studies; Protein Precursors - metabolism; Public health. Hygiene; Public health. Hygiene-occupational medicine; Regression analysis; Risk factors; Sample size; Type 2 diabetes; Endocrinopathy; Type 2 diabetes; Human; Endothelial cell; Renal function; Nutrition; Biological marker; Metabolic diseases; Cardiovascular disease; Endocrinology; Endothelium
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc08-2168

OBJECTIVE: The increased cardiovascular risk in diabetes has been linked to endothelial and renal dysfunction. The aim of this study was to investigate the role of stable fragments of the precursors of adrenomedullin, endothelin-1, vasopressin, and atrial natriuretic peptide in progression of cardiovascular disease in patients with diabetes. RESEARCH DESIGN AND METHODS: This was a prospective, observational study design with a composite end point (death or unexpected admission to hospital due to a cardiovascular event) on 781 patients with type 2 diabetes (54 events, median duration of observation 15 months). The four stable precursor peptides midregional adrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), COOH-terminal proendothelin-1 (CT-proET-1), and COOH-terminal provasopressin or copeptin (CT-proAVP) were determined at baseline, and their association to renal function and cardiovascular events was studied using stepwise linear and Cox logistic regression analysis and receiver operating characteristic analysis, respectively. RESULTS: MR-proADM, CT-proET-1, CT-proAVP, and MR-proANP were all elevated in patients with future cardiovascular events and independently correlated to serum creatinine. MR-proADM and MR-proANP were significant predictors of a future cardiovascular event, with MR-proANP being the stronger (area under the curve 0.802 ± 0.034, sensitivity 0.833, specificity 0.576, positive predictive value 0.132, and negative predictive value 0.978 with a cutoff value of 75 pmol/l). CONCLUSIONS: The four serum markers of vasoactive and natriuretic peptides are related to both kidney function and cardiovascular events, thus linking two major complications of diabetes, diabetic nephropathy and cardiovascular disease.