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Clinical Trial
. 2019 Jun 1;104(6):1917-1925.
doi: 10.1210/jc.2018-02195.

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

Sofia Enhörning  1   2 , Louise Brunkwall  1 , Irina Tasevska  1 , Ulrika Ericson  1 , Jenny Persson Tholin  1   3 , Margaretha Persson  1   3 , Guillaume Lemetais  4 , Tiphaine Vanhaecke  4 , Alberto Dolci  4 , Erica T Perrier  4 , Olle Melander  1   3
Affiliations
Clinical Trial

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

Sofia Enhörning et al. J Clin Endocrinol Metab. .

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.

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Figures

Figure 1.
Figure 1.
Recruitment and inclusion process. IBD, inflammatory bowel disease.
Figure 2.
Figure 2.
Study protocol.
Figure 3.
Figure 3.
Fasting glucose concentrations at baseline and after 6 wk of water intervention. fP, fasting plasma.
Figure 4.
Figure 4.
Changes in fasting glucose (difference between 6-wk and baseline glucose concentrations). (a) Participants with high baseline copeptin values (tertile 3) vs participants with lower baseline copeptin values (tertiles 1 and 2). (b) Participants with high copeptin (>6.1 pmol · L−1 in women and >10.7 pmol · L−1 in men) both at screening and at pilot vs participants with high copeptin at screening but low copeptin at pilot baseline.
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