THE VASOPRESSIN SYSTEM IN DIABETES MELLITUS, OBESITY AND THE METABOLIC SYNDROME

Background: Animal studies suggest that the arginine vasopressin (AVP) system plays a role in glucose and fat metabolism, but data from humans are limited. Method and results: We analysed plasma copeptin (copeptin), a stable C-terminal fragment of the AVP pro-hormone in the large, Swedish, population-based cohort Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC, n=6103). Using baseline (1991-1994) and longitudinal (register- and reinvestigation-based) data from MDC-CC (partly re-investigated 15.8 years later (n=2345)) we examined the association of increasing quartiles of copeptin (lowest quartile as reference) with prevalent diabetes (DM) and other components of the metabolic syndrome (MetS) at baseline, and incident DM, measures of obesity and microalbuminuria at follow up, using multivariable logistic regression. After adjusted for clinical and anthropometric risk factors, cystatin C, and C-reactive protein, increasing copeptin quartile (lowest quartile as reference) was associated with prevalent DM (Ptrend=0.04). Furthermore, copeptin quartile was after adjustment for age, sex, insulin and diabetes mellitus associated with prevalent hypertension (Ptrend=0.004), abdominal obesity (Ptrend=0.002), obesity (P=0.01), top quartile of CRP (Ptrend=0.007) and MetS (adjusted for age and sex only) (Ptrend<0.001). During 12.6 years of register-based follow up 174 subjects (4%) developed new-onset diabetes. The odds of developing DM increased across increasing quartile of copeptin, even after additional adjustment for baseline fasting glucose and insulin (adjusted odds ratios 1.0, 1.37, 1.79, and 2.09; Ptrend =0.004). The association with incident DM remained significant in analyses restricted to subjects with fasting whole blood glucose