The vasopressin system in the risk of diabetes and cardiorenal disease, and hydration as a potential lifestyle intervention

Background: Type 2 diabetes, chronic kidney disease (CKD) and its cardiovascular complications are increasing as health problems worldwide. These diseases are interrelated with overlapping occurrence and once diabetes is established, the risk of cardiorenal disease is dramatically elevated. Thus, a search for unifying modifiable risk factors is key for effective prevention. Summary: Elevated fasting plasma concentration of vasopressin, measured with the marker copeptin, predicts new onset type 2 diabetes as well as renal function decline. Furthermore, we recently showed that increased plasma copeptin concentration independently predicts the development of both CKD and other specified kidney diseases. In consequence, high copeptin is an independent risk factor for cardiovascular disease and premature mortality in both diabetes patients and in the general population. Vasopressin is released when plasma osmolality is high, and the easiest way to lower plasma vasopressin and copeptin concentration is to increase water intake. In a human water intervention experiment with 1 week of 3 L/day increased water intake, the one third of the participants with the greatest copeptin reduction (water responders) were those with a phenotype of low water intake (high habitual plasma copeptin and urine osmolality, and low urine volume). The water-responders had a copeptin reduction of 41% after 1 week of increased water intake compared to a control week; in contrast, a 3% reduction occurred in the other two thirds of the study participants. Among water responders, increased water intake also induced a reduction in fasting glucagon concentration. Key Messages: Elevated copeptin, a measure of vasopressin, is a risk marker of metabolic and cardiorenal diseases and may assist in the detection of individuals at higher risk for these diseases. Furthermore, individuals with high copeptin and other signs of low water intake may experience beneficial glucometabolic effects of increased water intake. Future randomized control trials investigating effects of hydration on glucometabolic and renal outcomes should focus on individuals with signs of low water intake including high plasma copeptin concentration.