Water Supplementation and Glucose Reduction in Adults with High Copeptin

Elevated copeptin, a stable surrogate marker for vasopressin, has been associated with reduced water intake and an elevated risk of diabetes. This study investigates the potential mechanisms by which water supplementation influences metabolic parameters in adults exhibiting high baseline copeptin levels.

Thirty-one healthy adults meeting specific inclusion criteria were enrolled. Participants had elevated copeptin concentrations (> 10.7 pmol·L−1 for men, > 6.1 pmol·L−1 for women), a 24-hour urine volume of less than 1.5 liters, and urine osmolality exceeding 600 mOsm·kg−1. The intervention protocol involved the daily addition of 1.5 liters of water over a six-week period.

Analysis of hormonal and metabolic markers revealed that fasting plasma adrenocorticotropic hormone (ACTH), cortisol levels, insulin, and glucagon were not significantly altered by the water intervention. However, a significant inverse relationship was observed between changes in fasting plasma copeptin and changes in fasting plasma ACTH (r = 0.76, p < 0.001). Additionally, decreases in fasting plasma copeptin correlated with reductions in fasting plasma glucagon (r = 0.39, p = 0.03).

When participants were stratified by baseline copeptin tertiles, a notable reduction in median fasting plasma ACTH was observed in the top tertile of copeptin levels, decreasing from 13.0 pmol L−1 to 7.7 pmol L−1 (p = 0.007). No significant reduction in ACTH occurred in the other two tertiles. These findings suggest that the glucose-lowering effect of water supplementation may be partly attributable to decreased activity within the hypothalamic–pituitary–adrenal axis.

This research provides mechanistic insight into the relationship between hydration status and metabolic regulation. While the study demonstrates a correlation between reduced copeptin and ACTH following water intervention, further investigation is required to establish causality. The findings are relevant for understanding physiological responses in individuals with specific metabolic profiles but should not be interpreted as clinical recommendations.