Plasma Copeptin, A Unifying Factor behind the Metabolic Syndrome

Context: Arginine vasopressin (AVP) is known to affect liver glycogenolysis, insulin, and glucagon secretion and pituitary ACTH release. We previously showed that high copeptin, the stable C-terminal fragment of AVP prohormone, is independently associated with hyperinsulinemia and future development of diabetes mellitus. Objective: The objective of the study was to examine whether plasma copeptin is associated with components of the metabolic syndrome (MetS) independently of insulin, diabetes mellitus, and environmental factors. Design, Setting, and Participants: This was a cross-sectional, population-based sample of 4742 subjects, aged 46-68 yr, 60% women, in Malmo, Sweden. Main Outcome Measure: Using multivariable logistic and linear regression, plasma copeptin was associated with components of the MetS. Results: Copeptin quartile (lowest quartile as reference) was, after adjustment for age, sex, insulin, and diabetes mellitus, associated with hypertension (odds ratios 1.04, 1.07, 1.31; P = 0.004), abdominal obesity (odds ratios 1.21, 1.16, 1.57; P = 0.002), obesity (odds ratios 1.25, 1.15, 1.49; P = 0.01), top quartile of c-reactive protein (odds ratios 1.11, 1.13, 1.32; P = 0.007), and MetS (adjusted for age and sex only) (odds ratios 1.53, 1.77, 1.86; P < 0.001). High copeptin levels were significantly associated with high fat intake, low physical activity, and borderline significantly associated with low socioeconomic status. The association between copeptin and components of the MetS was not affected after adjustment for these environmental factors. Conclusions: Our data suggest that increased activity of the AVP system is a unifying factor in the MetS and point to a new pharmacologically modifiable system of potential importance in the treatment of MetS and prevention of cardiovascular disease. (J Clin Endocrinol Metab 96: E1065-E1072, 2011)