The Hydration to Optimize Metabolism (H2O Metabolism) Pilot Study

High plasma concentration of vasopressin (i.e. antidiuretic hormone) is a novel and independent risk factor for type 2 diabetes, the metabolic syndrome, cardiovascular disease and premature death. The main physiological role of vasopressin is to maintain constant plasma osmolality. Previous studies in rats and a Mendelian randomization study in humans suggest causality between elevated vasopressin concentration and elevated plasma glucose concentration. As vasopressin can be suppressed by increasing water intake, the investigators hypothesize that water supplementation in individuals with high vasopressin can lower plasma glucose and prevent diabetes.

The aim of this pilot study is to test if six weeks of water supplementation of 1.5 Liters of extra water per day in low-drinkers with high copeptin can significantly alter hydration markers in general and reduce plasma copeptin in particular. Furthermore, the investigators also aim at investigating whether this 6-week water intervention can significantly reduce fasting plasma glucose concentration.

Inclusion criteria

• Provision of informed consent
• Age 20-75 years
• High plasma concentration of copeptin of >6.1 pmol/L in women and > 10.7 pmol/L in men
• 24-hour urine osmolality > 600 milliosmol (mosm) /kg water.

Exclusion criteria

• 24-hour urine volume >1.5 L
• Pregnancy or breastfeeding
• Plasma sodium <135 mmol/L
• Use of diuretics, lithium or SSRI drugs
• Chronic kidney disease (estimated glomerular filtration rate < 30mL/min)
• Heart failure
• Inflammatory bowel disease
• Type 1 diabetes or type 2 diabetes treated with insulin
• Vulnerable subjects (subjects with legal guardian, with loss of personal liberty)