Hydration to Optimize Metabolism

Study Overview
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Brief Summary
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This study evaluates hydration (1.5 L of water daily during 1 year) in the lowering of blood glucose concentration in adults with signs of dehydration (elevated levels of the vasopressin marker copeptin and high urine osmolality). Half of participants will in addition to lifestyle advice receive extra water on top of their habitual fluid intake, and the other half (control) will receive only lifestyle advice.

Detailed Description
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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 mendelian randomization studies in humans suggest causality between elevated vasopressin concentration and elevated plasma glucose concentration. As vasopressin can be suppressed by increasing water intake, we hypothesize that water supplementation in individuals with high vasopressin can lower plasma glucose and prevent diabetes. The aim of this project is to test in a single-centre randomized clinical trial (RCT), if water supplementation in subjects with high plasma levels of vasopressin (measured by a stable vasopressin marker of its precursor hormone called copeptin) can reduce fasting levels of glucose (primary outcome measure), risk of new-onset diabetes and other cardiometabolic risk factors (secondary outcome measures).

Official Title
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Hydration to Optimize Metabolism

Conditions
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Glucose, High Blood

Intervention / Treatment
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* Dietary Supplement: Water
* Behavioral: general life style advice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent, age 20-75 years with high plasma concentration of vasopressin (plasma concentration of copeptin of > 6.1 pmol/L in women and > 10.7 pmol/L in men) and 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 selective serotonin reuptake inhibitor (SSRI) drugs, chronic kidney disease (estimated glomerular filtration rate < 30 mL/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).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel-group RCT with two arms during 12 months. Subjects will be randomized to the water-intervention (in total 1.5 L increment daily on the top of habitual intake) and control groups (1:1) by computer-generated block randomization. Both groups will receive general life style advice (general oral and written advice on diet and physical activity).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Water intervention arm<br>The water intervention group will increase their habitual daily water intake with 1.5 L of tap water. Furthermore they will receive general life style advice (general oral and written advice on diet and physical activity). | Dietary Supplement: Water<br>* Increased daily water intake with 1.5 L of water on top of habitual water intake.<br>Behavioral: general life style advice<br>* oral and written advice on diet and physical activity<br>|
| Other: Control arm<br>Control group that will receive general life style advice (general oral and written advice on diet and physical activity). | Behavioral: general life style advice<br>* oral and written advice on diet and physical activity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting plasma glucose concentration (mmol/L) | Difference in change of fasting plasma glucose between water intervention arm and control arm. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diabetes incidence | Difference in diabetes incidence between water intervention arm and control arm. | 12 months | 
| Post oral glucose load glucose concentration (mmol/L) | Difference in change of post oral glucose load glucose concentration (mmol/L) between water intervention arm and control arm | 12 months | 
| Fasting insulin concentration (mIE/L) | Difference in change of fasting insulin (mIE/L) between water intervention arm and control arm | 12 months | 
| Post oral glucose load insulin concentration (mIE/L) | Difference in change of post oral glucose load insulin concentration (mIE/L) between water intervention arm and control arm | 12 months | 
| Fasting glucagon concentration (pmol/L) | Difference in change of fasting glucagon (pmol/L) between water intervention arm and control arm | 12 months | 
| Post oral glucose load glucagon concentration (pmol/L) | Difference in change of post oral glucose load glucagon concentration (pmol/L) between water intervention arm and control arm | 12 months | 
| HbA1c concentration (mmol/mol) | Difference in change of HbA1c (mmol/mol) between water intervention arm and control arm | 12 months | 
| Waist circumference (cm) | Difference in change of waist circumference (cm) between water intervention arm and control arm | 12 months | 
| Body mass index (kg/m^2) | Difference in change of body mass index (kg/m^2) between water intervention arm and control arm | 12 months | 
| Systolic blood pressure (mmHg) | Difference in change of systolic blood pressure (mmHg) between water intervention arm and control arm | 12 months | 
| Diastolic blood pressure (mmHg) | Difference in change of diastolic blood pressure (mmHg) between water intervention arm and control arm | 12 months | 
| Triglyceride concentration (mmol/L) | Difference in change of triglycerides (mmol/L) between water intervention arm and control arm | 12 months | 
| HDL cholesterol concentration (mmol/L) | Difference in change of HDL cholesterol (mmol/L) between water intervention arm and control arm | 12 months | 
| LDL cholesterol concentration (mmol/L) | Difference in change of LDL cholesterol (mmol/L) between water intervention arm and control arm | 12 months | 
| Apolipoprotein B concentration (g/L) | Difference in change of Apolipoprotein B (g/L) between water intervention arm and control arm | 12 months | 
| Apolipoprotein A1 concentration (g/L) | Difference in change of Apolipoprotein A1 (g/L) between water intervention arm and control arm | 12 months | 
| Urine albumin/creatinine ratio (g/mol) | Difference in change of urine albumin/creatinine ratio (g/mol) between water intervention arm and control arm | 12 months | 
| Estimated glomerular filtration rate (mL/min/1,73 m2) | Difference in change of estimated glomerular filtration rate (mL/min/1,73 m2) between water intervention arm and control arm | 12 months | 
| Creatinine clearance (mL/min) | Difference in change of creatinine clearance (mL/min) between water intervention arm and control arm | 12 months | 
| Fasting cortisol concentration (nmol/L) | Difference in change of fasting cortisol (nmol/L) between water intervention arm and control arm | 12 months | 
| Fasting adrenocorticotropic hormone concentration (pmol/L) | Difference in change of fasting adrenocorticotropic hormone (pmol/L) between water intervention arm and control arm | 12 months | 
| C-reactive protein concentration (mg/L) | Difference in change of C-reactive protein (mg/L) between water intervention arm and control arm | 12 months | 
| Hair cortisol concentration (pg/mg) | Difference in change of hair cortisol (pg/mg) between water intervention arm and control arm. Hair cortisol is a measure of chronic stress exposure 3 months prior to sampling. | 12 months between samplings | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OGTT, hydration, water, vasopressin, copeptin, glucose, insulin, glucagon