Abstract

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, 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.ResultsAfter 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.ConclusionsBoth 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.

Highlights

  • Vasopressin (VP) is released from the posterior pituitary gland mainly in conditions of increased plasma osmolality or hypovolemia

  • We showed that subjects with high copeptin concentration have an increased risk of all components of the metabolic syndrome [11, 14, 15] as well as cardiovascular disease and premature mortality, both in diabetics and non-diabetics [16,17,18]

  • As high copeptin has been repeatedly shown to be a strong independent risk factor for diabetes, the second aim of our study was to investigate if a reduction of copeptin by increased water intake for 1 week may influence glycemia, insulin or glucagon concentrations

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Summary

Introduction

Vasopressin (VP) is released from the posterior pituitary gland mainly in conditions of increased plasma osmolality or hypovolemia. Apart from maintaining plasma osmolality by mediating water reabsorption in conditions of low water intake, VP has many other physiological functions. VP plays a role in the hypothalamic–pituitary–adrenal axis by mediating adrenocorticotropic hormone release from the anterior pituitary [4, 5]. We showed that subjects with high copeptin concentration have an increased risk of all components of the metabolic syndrome [11, 14, 15] as well as cardiovascular disease and premature mortality, both in diabetics and non-diabetics [16,17,18]

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