OBJECTIVE Plasma copeptin, a surrogate for vasopressin, has been associated with a decline in renal function and albuminuria in population-based studies as well as with progression of diabetic nephropathy in people with type 2 diabetes. We assessed the risk of kidney and coronary events and all-cause mortality associated with plasma copeptin in people with type 1 diabetes. RESEARCH DESIGN AND METHODS Plasma copeptin was measured in baseline samples of the GENEDIAB (n = 398; 56% male; mean 6 SD

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... ge 45 6 12 years and diabetes duration 28 6 10 years) and GENESIS (n = 588; 52% male; age 42 6 11 years; diabetes duration 27 6 9 years) cohorts. Follow-up data were available for 218 GENEDIAB and 518 GENESIS participants. Median duration of follow-up was 10.2 and 5.0 years, respectively. RESULTS Upper sex-specific tertiles of copeptin were associated with a higher incidence of end-stage renal disease (ESRD) during follow-up (hazard ratio [HR] for third vs. first tertile 26.5 [95% CI 8.0-163.3; P < 0.0001]; analysis in pooled cohorts adjusted for age, sex, duration of diabetes, and cohort membership). The highest tertile of copeptin was also associated with incidence of myocardial infarction or coronary revascularization (HR 2.2 [95% CI 1.2-4.0]; P = 0.01) and all-cause mortality (HR 3.3 [95% CI 1.8-6.5]; P < 0.0001) during follow-up. CONCLUSIONS Plasma copeptin is a predictor for the risk of ESRD, coronary heart disease, and allcause mortality in people with type 1 diabetes. Results are consistent with data from experimental and epidemiological studies, suggesting that high circulating levels of vasopressin are deleterious to renal function. Circulating levels of vasopressin (or antidiuretic hormone) are increased in people with type 1 or type 2 diabetes and in animal models with spontaneous or streptozotocin-induced diabetes (1). Vasopressin is cosecreted into the blood by the neurohypophysis in an equimolar amount with copeptin, the COOH-terminal portion of the preprovasopressin peptide. The main stimuli for the secretion of vasopressin are an increase in plasma osmolality and/or a decrease in arterial circulating