Effect of increased water intake on plasma copeptin in healthy adults

Inter-individual variation in median plasma copeptin is associated with incident type 2 diabetes mellitus, progression of chronic kidney disease, and cardiovascular events. In this study, we examined whether 24-h urine osmolality was associated with plasma copeptin and whether increasing daily water intake could impact circulating plasma copeptin. This trial was a prospective study conducted at a single investigating center. Eighty-two healthy adults (age 23.6 +/- 2.9 years, BMI 22.2 +/- 1.5 kg/m(2), 50% female) were stratified based upon habitual daily fluid intake volumes: arm A (50-80% of EFSA dietary reference values), arm B (81-120%), and arm C (121-200%). Following a baseline visit, arms A and B increased their water intake to match arm C for a period of 6 consecutive weeks. At baseline, plasma copeptin was positively and significantly associated with 24-h urine osmolality (p = 0.002) and 24-h urine specific gravity (p = 0.003) but not with plasma osmolality (p = 0.18), 24-h urine creatinine (p = 0.09), and total fluid intake (p = 0.52). Over the 6-week follow-up, copeptin decreased significantly from 5.18 (3.3;7.4) to 3.90 (2.7;5.7) pmol/L (p = 0.012), while urine osmolality and urine specific gravity decreased from 591 +/- 206 to 364 +/- 117 mOsm/kg (p < 0.001) and from 1.016 +/- 0.005 to 1.010 +/- 0.004 (p < 0.001), respectively. At baseline, circulating levels of copeptin were positively associated with 24-h urine concentration in healthy young subjects with various fluid intakes. Moreover, this study shows, for the first time, that increased water intake over 6 weeks results in an attenuation of circulating copeptin. NCT02044679.