Journal
CIRCULATION
Volume 121, Issue 19, Pages 2102-U51Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.109.909663
Keywords
arginine vasopressin; copeptin; diabetes mellitus; epidemiology; risk factors
Funding
- Swedish Medical Research Council
- Swedish Heart and Lung Foundation
- Medical Faculty of Lund University
- Malmo University Hospital
- Albert Pahlsson Research Foundation
- Crafoord Foundation
- Ernhold Lundstroms Research Foundation
- Region Skane
- Hulda and Conrad Mossfelt Foundation
- King Gustaf V and Queen Victoria Foundation
- Lennart Hanssons Memorial Fund
- Wallenberg Foundation
- NIH [K23-HL-080025, R01-HL-086875, R01-HL-083197, R01-DK-081572]
- Doris Duke Charitable Foundation
- Burroughs Wellcome Fund
- American Heart Association
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Background-Animal studies suggest that the arginine vasopressin system may play a role in glucose metabolism, but data from humans are limited. Methods and Results-We analyzed plasma copeptin (copeptin), a stable C-terminal fragment of the arginine vasopressin prohormone. Using baseline and longitudinal data from a Swedish population-based sample (n=4742; mean age, 58 years; 60% women) and multivariable logistic regression, we examined the association of increasing quartiles of copeptin (lowest quartile as reference) with prevalent diabetes mellitus at baseline, insulin resistance (top quartile of fasting plasma insulin among nondiabetic subjects), and incident diabetes mellitus on long-term follow-up. New-onset diabetes mellitus was ascertained through 3 national and regional registers. All models were adjusted for clinical and anthropometric risk factors, cystatin C, and C-reactive protein. In cross-sectional analyses, increasing copeptin was associated with prevalent diabetes mellitus (P=0.04) and insulin resistance (P < 0.001). During 12.6 years of follow-up, 174 subjects (4%) developed new-onset diabetes mellitus. The odds of developing diabetes mellitus increased across increasing quartiles of copeptin, even after additional adjustment for baseline fasting glucose and insulin (adjusted odds ratios, 1.0, 1.37, 1.79, and 2.09; P for trend=0.004). The association with incident diabetes mellitus remained significant in analyses restricted to subjects with fasting whole blood glucose < 5.4 mmol/L at baseline (adjusted odds ratios, 1.0, 1.80, 1.92, and 3.48; P=0.001). Conclusions-Elevated copeptin predicts increased risk for diabetes mellitus independently of established clinical risk factors, including fasting glucose and insulin. These findings could have implications for risk assessment, novel antidiabetic treatments, and metabolic side effects from arginine vasopressin system modulation. (Circulation. 2010; 121: 2102-2108.)
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