Water Supplementation Reduces Copeptin and Plasma Glucose in Adults With High Copeptin: The H2O Metabolism Pilot Study

J Clin Endocrinol Metab. 2019 Jun 1;104(6):1917-1925. doi: 10.1210/jc.2018-02195.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT03574688.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Blood Glucose / analysis*
  • Blood Glucose / physiology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Drinking / physiology*
  • Fasting / blood
  • Fasting / physiology
  • Female
  • Glycopeptides / blood*
  • Glycopeptides / metabolism
  • Healthy Volunteers
  • Humans
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Pilot Projects
  • Treatment Outcome
  • Urine / chemistry
  • Urine / physiology
  • Vasopressins / blood
  • Vasopressins / metabolism
  • Water / administration & dosage*
  • Young Adult

Substances

  • Blood Glucose
  • Glycopeptides
  • copeptins
  • Water
  • Vasopressins

Associated data

  • ClinicalTrials.gov/NCT03574688