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Objective: Because elevated copeptin, a marker of vasopressin, is linked to low water intake and high diabetes risk, we tested the effect of water supplementation on copeptin and fasting glucose., Design, Setting, and Participants: Thirty-one healthy adults with high copeptin (>10.7 pmol · L-1 in men and >6.1 pmol·L-1 in women) identified in a population-based survey from 2013 to 2015 and with a current 24-hour urine osmolality of >600 mOsm · kg-1 were included., Intervention: Addition of 1.5 L water daily on top of habitual fluid intake for 6 weeks., Main Outcome Measure: Pre- and postintervention fasting plasma copeptin concentrations., Results: Reported mean water intake increased from 0.43 to 1.35 L · d-1 (P < 0.001), with no other observed changes in diet. Median (interquartile range) urine osmolality was reduced from 879 (705, 996) to 384 (319, 502) mOsm · kg-1 (P < 0.001); urine volume increased from 1.06 (0.90, 1.20) to 2.27 (1.52, 2.67) L · d-1 (P < 0.001); and baseline copeptin decreased from 12.9 (7.4, 21.9) pmol · L-1 to 7.8 (4.6;11.3) pmol · L-1 (P < 0.001). Water supplementation reduced fasting plasma glucose from a mean (SD) of 5.94 (0.44) to 5.74 (0.51) (P = 0.04). The water-associated reduction of both fasting copeptin and glucose concentration in plasma was most pronounced in participants in the top tertile of baseline copeptin., Conclusions: Water supplementation in persons with habitually low water consumption and high copeptin levels is effective in lowering copeptin. It appears a safe and promising intervention with the potential of lowering fasting plasma glucose and thus reducing diabetes risk. Further investigations are warranted to support these findings., (Copyright © 2019 Endocrine Society.)

Purpose: High plasma copeptin, a marker of vasopressin, predicts diabetes mellitus. We tested if copeptin could be suppressed by increased water intake in healthy individuals, and if a water-induced change in copeptin was accompanied by altered concentrations of glucose, insulin or glucagon., Methods: Thirty-nine healthy individuals underwent, in random order, 1 week of high water intake (3 L/day on top of habitual intake) and 1 week of normal (habitual) fluid intake (control). Fasting plasma concentrations of copeptin, glucose, insulin and glucagon were compared between the ends of both periods. Furthermore, acute copeptin kinetics were mapped for 4 h after ingestion of 1 L of water., Results: After acute intake of 1 L water, copeptin was significantly reduced within 30 min, and reached maximum reduction within 90 min with on average 39% reduction (95% confidence interval (95 CI) 34-45) (p < 0.001) and remained low the entire test period (4 h). One week of increased water intake led to a 15% reduction (95 CI 5-25) (p = 0.003) of copeptin compared to control week. The greatest reduction occurred among subjects with habitually high copeptin and concentrated urine ("water-responders"). Water-responders had significant water-induced reduction of glucagon, but glucose and insulin were unaffected., Conclusions: Both acute and 1 week extra water intake potently reduced copeptin concentration. In those with the greatest decline (water-responders), who are typically low drinkers with high baseline copeptin, water induced a reduction in fasting glucagon. Long-term trials assessing the effect of water on glucometabolic traits should focus on low-water drinkers with high copeptin concentration.

Background: The prevalence of chronic kidney disease (CKD) is increasing worldwide. The identification of factors contributing to its progression is important for designing preventive measures. Previous studies have suggested that chronically high vasopressin is deleterious to renal function. Here, we evaluated the association of plasma copeptin, a surrogate of vasopressin, with the incidence of CKD in the general population., Methods: We studied 3 European cohorts: DESIR (n = 5,047; France), MDCS-CC (n = 3,643; Sweden), and PREVEND (n = 7,684; the Netherlands). Median follow-up was 8.5, 16.5, and 11.3 years, respectively. Pooled data were analyzed at an individual level for 4 endpoints during follow-up: incidence of stage 3 CKD (estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m2); the KDIGO criterion "certain drop in eGFR"; rapid kidney function decline (eGFR slope steeper than -3 ml/min/1.73 m2/yr); and incidence of microalbuminuria., Results: The upper tertile of plasma copeptin was significantly and independently associated with a 49% higher risk for stage 3 CKD (P < 0.0001); a 64% higher risk for kidney function decline, as defined by the KDIGO criterion (P < 0.0001); a 79% higher risk for rapid kidney function decline (P < 0.0001); and a 24% higher risk for microalbuminuria (P = 0.008)., Conclusions: High copeptin levels are associated with the development and the progression of CKD in the general population. Intervention studies are needed to assess the potential beneficial effect on kidney health in the general population of reducing vasopressin secretion or action., Funding: INSERM and Danone Research Centre for Specialized Nutrition.

Background: Our aim was to test if plasma copeptin, a stable surrogate marker of arginine vasopressin, predicts decline of glomerular filtration rate (GFR) and risk of chronic kidney disease (CKD)., Methods: We measured copeptin and renal function at the Malmö Diet and Cancer Cardiovascular Cohort baseline exam and reassessed renal function after a follow-up time of 16.6 ± 1.5 years (n = 3,186). Furthermore, we defined CKD based on an estimated GFR (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) <60 (CKD&#95;60MDRD), <45 (CKD&#95;45MDRD) and <30 (CKD&#95;30MDRD) ml/min/1.73 m2., Results: After multivariate adjustment (gender, age, baseline eGFR, smoking status, systolic blood pressure, antihypertensive treatment and follow-up time), copeptin (beta-coefficient per 1 SD increment of copeptin) was independently associated with significantly greater annual decline of eGFR (ml/min/1.73 m2) according to the MDRD formula (OR 0.057, 95% CI 0.022-0.093; p = 0.001) as well as according to the CKD Epidemiology Collaboration (CKD-EPI) formula (OR 0.050, 95% CI 0.022-0.077; p < 0.001). Each SD increment of copeptin independently predicted incident CKD&#95;60MDRD (OR 1.19, 95% CI 1.04-1.36; p = 0.010), CKD&#95;45MDRD (OR 1.33, 95% CI 1.04-1.71; p = 0.026) and CKD&#95;30MDRD (OR 3.69, 95% CI 1.41-9.66; p = 0.008). The relationship between copeptin and CKD defined by CKD-EPI gave similar results., Conclusion: Our data suggest that increased levels of copeptin independently predict decline in eGFR and greater risk of new-onset CKD., (© 2016 S. Karger AG, Basel.)

Objective: In a middle-aged population, it was recently shown that the stable vasopressin marker plasma copeptin (copeptin) predicts development of diabetes mellitus, diabetic heart disease and death. Here, it was hypothesised whether copeptin predicts a risk of coronary artery disease (CAD), and cardiovascular mortality in an older population., Methods: Between 2002 and 2006, fasting plasma copeptin was examined and measured in 5386 participants of a population-based longitudinal study (mean age 69.4±6.2 years, 69.8% males) and related copeptin to risk of CAD (first myocardial infarction or coronary revascularisation), cardiovascular and total mortality during a mean follow-up time of 6.5 years using multivariate adjusted (age, gender, systolic blood pressure, antihypertensive therapy, smoking, diabetes, low-density lipoprotein and high-density lipoprotein cholesterol) Cox proportional hazards models., Results: Among subjects free from CAD at baseline, the multivariate adjusted HR (95% CI) per 1 SD increment of log-transformed copeptin for risk of CAD development was 1.20 (1.08 to 1.33) (p=0.001). There was a borderline significant interaction between diabetes and copeptin on CAD risk (p=0.08) with higher copeptin-associated risk in subjects with diabetes (1.49 (1.14 to 1.95); p=0.004) than in non-diabetic subjects (1.15 (1.02 to 1.50); p=0.02). Moreover, each SD increment of copeptin independently predicted total mortality (1.31 (1.21 to 1.41); p<0.001), an effect driven by the copeptin association with cardiovascular mortality (1.36 (1.21 to 1.53); p<0.001). The absolute risks for CAD were 4.9%, 9.3% and 2.9%, total and CV mortality were 4.9%, 9.3% and 2.9% in quartile 1, 7.1%, 9.4% and 3.5% in quartile 2, 8.3%, 14.2% and 5.6% in quartile 3, and 10.3%, 23.3% and 9.1% in quartile 4, respectively., Conclusions: Copeptin predicts development of CAD and cardiovascular mortality both in diabetics and non-diabetics., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

This study investigated if copeptin is affected by high salt intake and whether any salt-induced changes in copeptin are related to the degree of salt sensitivity. The study was performed on 20 men and 19 women. In addition to meals containing 50 mmol NaCl daily, capsules containing 100 mmol NaCl and corresponding placebo capsules were administered during 4 weeks each, in random order. Measurements of 24 h blood pressure, body weight, 24 h urinary volume, and fasting plasma copeptin were performed at high and low salt consumption. Copeptin increased after a high compared to low dietary salt consumption in all subjects 3,59 ± 2,28 versus 3,12 ± 1,95 (P = 0,02). Copeptin correlated inversely with urinary volume, at both low (r = -0,42; P = 0,001) and high (r = -0,60; P < 0,001) salt consumption, as well as with the change in body weight (r = -0,53; P < 0,001). Systolic salt sensitivity was inversely correlated with salt-induced changes of copeptin, only in females (r = -0,58; P = 0,017). As suppression of copeptin on high versus low salt intake was associated with systolic salt sensitivity in women, our data suggest that high fluid intake and fluid retention may contribute to salt sensitivity.