Effects of hydration on plasma copeptin, glycemia and gluco-regulatory hormones: a water intervention in humans

PurposeHigh 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.MethodsThirty-nine healthy individuals underwent, in random order, 1week of high water intake (3L/day on top of habitual intake) and 1week 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 4h after ingestion of 1L of water.ResultsAfter acute intake of 1L water, copeptin was significantly reduced within 30min, and reached maximum reduction within 90min with on average 39% reduction (95% confidence interval (95 CI) 34-45) (p<0.001) and remained low the entire test period (4h). 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.ConclusionsBoth acute and 1week 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.