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

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.

High water intake and low urine osmolality are associated with favorable metabolic profile at a population level: low vasopressin secretion as a possible explanation

“…The current study is complementary to and expands our previous finding from an experimental study in humans in which we showed that individuals with low water intake (measured as low 24 h urine volume, high 24 h u-Osm and high copeptin) express a reduction of fasting plasma glucose as a response to increased water intake [9]. In another previous study, we showed that increased water intake in individuals with low water intake was associated with a reduction of the diabetogenic hormone glucagon [20], implicating glucagon as a possible contributing factor to elevated fasting glucose among individuals with low water intake.…”

“…Elevated plasma copeptin, a reliable marker of VP secretion, has previously been associated with multiple components of the metabolic syndrome [2][3][4] and with increased risk of diabetes development [5][6][7]. Previous experimental studies [8,9] and a Mendelian randomization study [10] points at a causal association between elevated copeptin concentration and increased metabolic risk. It can be speculated that this relationship may be explained by effects mediated by VP receptors expressed in the liver, the pancreas and in the anterior pituitary gland, which potentially could affect glucose metabolism in many different ways by inducing gluconeogenesis, glycogenolysis, glucagon secretion, and increased cortisol release [11][12][13][14][15][16][17].…”

Low hydration status may be associated with insulin resistance and fat distribution: analysis of the Korea National Health and Nutrition Examination Survey (KNHANES) 2008–2010

“…Therefore, the potential benefit of improved hydration status on glucose metabolism should be tested in future clinical trials. Actually, a recent study showed that, in adults with high copeptin levels, an increased hydration induced not only a significant decline in copeptin (as expected) but also a significant decline in glycaemia (37) . In the present study, we found that increased USG was associated with increased trunk fat and decreased leg fat, resulting in increased TLR, after adjusting for age, sex, habitual patterns, various cardiovascular risks and plain water and energy intakes.…”

Underhydration Is Associated with Obesity, Chronic Diseases, and Death Within 3 to 6 Years in the U.S. Population Aged 51–70 Years

“…Longitudinal data suggest parallel relationships between various correlates of osmotic stress on cells and risk of the metabolic syndrome. Behavioral determinants of hyperosmotic stress on cells, such as salt intake, lower absolute water intake, and intake of hypertonic beverages such as sugar-sweetened beverages instead of drinking water [97][98][99][100][101]; blood biomarker measures of hyperosmotic stress on cells, such as serum hypernatremia, hypertonicity, or hyperosmolality [26,32,33,38,88,102]; intracellular measures of biochemical response to hyperosmotic cell shrinkage such as upregulation of the serumand glucocorticoid-inducible kinase 1 (SGK1) [103,104]; and physiologic measures of response to hyperosmotic cell shrinkage, such as increases in plasma copeptin [18,19,[105][106][107][108], are independently associated with incident metabolic dysregulation and/or chronic disease risk.…”