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Plasma Carboxy-Terminal Provasopressin (Copeptin): A Novel Marker of Insulin Resistance and Metabolic Syndrome

Division of Cardiovascular Diseases (U.S., M.K., I.J.K.), Mayo Clinic, Rochester, Minnesota 55905; Research Department of BRAHMS AG (N.G.M., A.B., J.S.), Biotechnology Centre, D-16761 Hennigsdorf/Berlin, Germany; and the Department of Medicine (Geriatrics) (T.H.M.), University of Mississippi Medical Center, Jackson, Mississippi 39216

Address all correspondence and requests for reprints to: Iftikhar J. Kullo, M.D., Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street S.W., Rochester, Minnesota 55905. E-mail: kullo.iftikhar{at}mayo.edu.

Context: Stress-mediated hypothalamic-pituitary-adrenal axis activation, regulated by arginine vasopressin (AVP), may have a role in the pathophysiology of metabolic syndrome (MetSyn).

Objective: The objective of the study was to investigate whether plasma C-terminal provasopressin fragment (copeptin), a surrogate for circulating AVP, was associated with measures of insulin resistance and presence of MetSyn.

Design, Setting, and Participants: This was a multicenter, community-based study, investigating novel biomarkers for vascular disease. Participants included 1293 African-Americans (AA) (64 ± 9 yr) and 1197 non-Hispanic whites (NHW) (59 ± 10 yr) belonging to hypertensive sibships.

Main Outcome Measures: Plasma copeptin levels were measured by an immunoluminometric assay. MetSyn was defined per Adult Treatment Panel III criteria. Generalized estimating equations were used to assess whether plasma copeptin was associated with measures of insulin resistance and MetSyn.

Results: The prevalence of MetSyn was 50% in AA and 49% in NHW. In each group, after adjustment for age and sex, plasma copeptin levels significantly correlated with body mass index, fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance, triglycerides, and (inversely) high-density lipoprotein cholesterol (P < 0.05 for each variable). In multivariable logistic regression models that adjusted for age, sex, smoking, statin use, serum creatinine, education, physical activity, and diuretic use, plasma copeptin levels in the highest quartile were associated with an increased odds ratio of having MetSyn compared with bottom quartile: odds ratio (95% confidence interval) in AA, 2.07 (1.45–2.95); in NHW, 1.74 (1.21–2.5).

Conclusions: Our findings indicate a novel cross-sectional association between plasma copeptin and measures of insulin resistance and MetSyn.