Gilberto Velho1, Ray El Boustany2, Guillaume Lefèvre3, Kamel Mohammedi2,4, Frédéric Fumeron2,5, Louis Potier2,4,5, Lise Bankir2,6, Nadine Bouby2,6, Samy Hadjadj7,8,9,10, Michel Marre2,4,5, Ronan Roussel2,4,5. 1. INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France gilberto.velho@inserm.fr. 2. INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France. 3. Assistance Publique Hôpitaux de Paris, Hôpitaux Universitaires Est Parisien-Tenon, Service de Biochimie et Hormonologie, Paris, France. 4. Assistance Publique Hôpitaux de Paris, Hôpital Bichat, DHU FIRE, Départment de Diabétologie, Endocrinologie et Nutrition, Paris, France. 5. Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France. 6. Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, Paris, France. 7. Départment de Endocrinologie et Diabétologie, CHU de Poitiers, Poitiers, France. 8. INSERM, Unité de Recherche 1082, Poitiers, France. 9. INSERM, CIC 1402, Poitiers, France. 10. Université de Poitiers, UFR de Médecine et Pharmacie, Poitiers, France.
Abstract
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 ± SD age 45 ± 12 years and diabetes duration 28 ± 10 years) and GENESIS (n = 588; 52% male; age 42 ± 11 years; diabetes duration 27 ± 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 all-cause 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.
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 ± SD age 45 ± 12 years and diabetes duration 28 ± 10 years) and GENESIS (n = 588; 52% male; age 42 ± 11 years; diabetes duration 27 ± 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 all-cause 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.
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