Abstract
Elevated copeptin, a surrogate marker of vasopressin, is linked to low water intake and increased diabetes risk. Water supplementation in habitual low-drinkers with high copeptin significantly lowers both fasting plasma (fp) copeptin and glucose. This study aims at investigating possible underlying mechanisms. Thirty-one healthy adults with high copeptin (> 10.7 pmol·L−1 (men), > 6.1 pmol−1 (women)) and 24-h urine volume of < 1.5L and osmolality of > 600 mOsm·kg−1 were included. The intervention consisted of addition of 1.5 L water daily for 6 weeks. Fp-adrenocorticotropic hormone (ACTH), fp-cortisol, 24-h urine cortisol, fasting and 2 h (post oral glucose) insulin and glucagon were not significantly affected by the water intervention. However, decreased (Δ baseline-6 weeks) fp-copeptin was significantly associated with Δfp-ACTH (r = 0.76, p < 0.001) and Δfp-glucagon (r = 0.39, p = 0.03), respectively. When dividing our participants according to baseline copeptin, median fp-ACTH was reduced from 13.0 (interquartile range 9.2–34.5) to 7.7 (5.3–9.9) pmol L−1, p = 0.007 in the top tertile of copeptin, while no reduction was observed in the other tertiles. The glucose lowering effect from water may partly be attributable to decreased activity in the hypothalamic–pituitary–adrenal axis.ClinicalTrials.gov: NCT03574688.
Highlights
Elevated copeptin, a surrogate marker of vasopressin, is linked to low water intake and increased diabetes risk
Given the pleiotropic effects of VP mediated through different receptors in several target organs, this study aims at investigating possible underlying mechanisms behind the glucose reduction observed in the pilot study after 6 weeks of VP-suppressing water treatment and includes a detailed investigation of hormones involved in glucose regulation
Out of the 24% of the individuals participating in the Malmö Offspring Study with high copeptin concentrations (> 6.1 pmol·L−1 in women and > 10.7 pmol·L−1 in men), 277 were contacted, and 34 individuals were eligible and included in the study (82 were not reached, 93 were not interested and 38 were excluded; out of 64 qualified individuals, 30 could not be included due to either low urine osmolality or high urine volume)
Summary
A surrogate marker of vasopressin, is linked to low water intake and increased diabetes risk. Vasopressin (VP) is the key hormone involved in body fluid balance by maintaining constant plasma osmolality This is achieved by osmoreceptor-stimulated VP release mediating water reabsorption through VP 2 (V2) receptors in the renal collecting ducts in conditions of low water intake[1]. High water intake has been associated with a favourable metabolic profile[22] and decreased diabetes r isk[23,24]. Taken together, these results suggest that the link between high VP and cardiometabolic risk may be modifiable by increased water intake. Our published pilot study showed that 1.5L of increased water intake per day during 6 weeks significantly lowered copeptin secretion and fp glucose[25]
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