Att dricka lagom mycket vatten befrämjar hälsan och ger ett långt och lyckligt liv (?)
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Att dricka lagom mycket vatten befrämjar
hälsan och ger ett långt och lyckligt liv (?)
Major MinorMinor Homeostasis
WATER REABSORPTION
AVP
VASOPRESSIN: FRIEND OR ENEMY?
V2RV1AR
V1BR
WATER INTAKE
V2R
Antidiuresis
V1bR
ACTH
secretion
V1aR
Vasoconstriction
Platelet aggregation
V1aR
Glycogenolysis
Gluconeogenesis
Insulin &
glucagon
secretion
CARDIO-RENAL AND METABOLIC EFFECTS OF VASOPRESSIN (VP)
V1bR V1bR
Cortisol
secretion
ABDOMINAL OBESITY
INSULIN RESISTANCE
HYPERTENSION
DIABETES&
CARDIOVASCULAR
DISEASE
DYSLIPIDEMIA
CUSHINGS SYNDROME
AUTONOMOUS OVERPRODUCTION OF CORTISOL
Gillies et al, Nature 1982 & Tanoue et al, J Clin Invest 2004
++
AVP STIMULATION OF V1B
RECEPTORS
VASOPRESSIN PRECURSOR
HORMONE
AVP NEUROPHYSIN II COPEPTIN
(CT-proAVP)
OR=1.78 (0.78-4.16)
OR=1.92 (0.84-4.38)
OR=3.48 (1.58-7.65)
OR incident diabetes
P trend=0.001Q copeptin
Q4
Q3
Q2
Q1
Circulation 2010;121:2102-2108
Copeptin >6.1 pmol/L in women
Copeptin >10.7 pmol/L in men
3-4 times increased risk of diabetes
=equally strong risk factor as obesity
Circulation 2010;121:2102-2108
Analysis multivariate adjusted for all diabetes risk factors including baseline fasting glucose levels
Ptrend=0.01Ptrend=0.02
Hypertension Abdominal obesity
Ptrend<0.001
Metabolic syndrome
Enhörning et al. J Clin Endocrinol Metab 2011;96:E1065-E1072
HIGH COPEPTIN (20-25% OF POPULATION) HAVE A PHENOTYPE
RESEMBLING A MILD FORM OF CUSHINGS SYNDROME
AVP
V2RV1AR
V1BR
Mean age 70 years
5.6 years of follow-
up
Copeptin >6.1 pmol/L in women
Copeptin >10.7 pmol/L in men
doubles risk of cardiovascular mortality
WHICH IS THE EASIEST AND MOST
EFFICIENT WAY TO LOWER
VASOPRESSIN?
Obese Low-VP
A
Lean
Obese Norm-VP Obese High-VP
Taveau et al. Diabetologia 2015
Liver steatosis is prevented by high water intake (=low VP)
Drinking 1 L of water in healthy humans (n=39) produces a
rapid and sustained suppression of vasopressin (copeptin) in
plasma (average reduction = 42%)
0-240 minutes post 1L water
P<0.0001
Enhörning et al 2017
random order
cross over
Time control
3L water/day
N=39, HEALTHY SUBJECTS
ONE WEEK HIGH WATER IN HEALTHY VOLONTEERS
3 L water/day Vasopressin
(Copeptin)
Glucose,
Insulin,
Glucagon ?
Enhörning et al 2017
N=39, age 53 y, 23% males, BMI 25 kg/m2
Habitual parameters of hydration status (at the end of control week)
Non water-responders (n=25)
Water-responders (n=12)
P-value
P-copeptin (pmol/l) 3.64 (3.22-5.52) 7.46 (6.02-9.53) <0.001
U-osmolality (mOsm/kg) 455.0 (316.5-562.5) 664.0 (473.5-962.8) 0.008
U-volume (ml/24h) 1411 (1280-2194) 1036 (768-1357) 0.005
Average water-induced reduction of copeptin (15%; P=0.003)
Non water-responders (n=25)
Water-responders (n=12)
COPEPTIN REDUCTION (%)
2.7% (NS) 41 % (P<0.001)
COPEPTIN REDUCTION (pmol/L)
0.24 pmol/L (NS) 3.1 pmol/L (P<0.001)
Enhörning et al 2017
WATER RESPONDER: *Signs of low-normal water-intake
*High copeptin-high diabetes risk
Major MinorMinor Homeostasis
IN WHOM IS WATER LIKELY TO BE SUITABLE FOR DIABETES PREVENTION?
AVPAVP AVP
AVPAVP
AVPAVP
LOW-NORMAL WATER DRINKERS (HIGH COPEPTIN):
**HIGH DIABETES RISK (EQUAL OR GREATER THAN OBESITY)
***WATER RESPONDERS (=SUBSTANTIAL REDUCTION OF VP/COPEPTIN)
Copeptin (Vasopressin):
>6.1 pmol/L in females
>10.7 pmol/L in males
Wate
r-in
duced c
hange o
f fp
-glu
cagon (
resid
uals
)
NON WATER-
RESPONDERS
WATER-
RESPONDERS
P<0.05
P<0.05
WATER-INDUCED SUPPRESSION OF COPEPTIN (1 WEEK) LEADS TO
REDUCTION OF FASTING GLUCAGON CONCENTRATION
(NO DIFFERENCE IN GLYCEMIA OR INSULIN)
Enhörning et al 2017
HYDRATION TO OPTIMIZE METABOLISM
“H2O-METABOLISM”
SCAPIS-Malmö
N=5.000Malmö Offspring Study
N=5.000
Big3
N=10.000
Measurement of copeptin (vasopressin):
>6.1 pmol/L in females / >10.7 pmol/L in males
25% of population 50-65y
Inclusion /Exclusion criteria
Invitation, informed consent
Randomisation
Diet and life style advise
+ 1.5 L water/day
N=450
Diet and life style advise
N=450
12 months follow-up including coaching,
dose adjustment based on 24-h osmolarity
EpiHealth
N=7.000
Major MinorMinor Homeostasis
AVPAVP AVP
AVPAVP
AVPAVP
Copeptin (Vasopressin)
>6.1 pmol/L in females
>10.7 pmol/L in males
*HIGH COPEPTIN HIGH RISK OF DIABETES, CVD AND PREMATURE MORTALITY
*HIGH COPEPTIN ARE LOW WATER DRINKERS BUT RESPOND WELL ON HYDRATION
*HIGH COPEPTIN: DOES HYDRATION OF THESE INDIVIDUALS LOWER DM/CKD/CVD RISK?
20-25% of
the
population
THANK YOU VERY MUCH
FOR YOUR ATTENTION
Sofia Enhörning
Irina Tasevska
Anders Christensson
Widet Gallo
Philippe Burri
Margaretha Persson
Charlotte Hjerpe
Jenny Persson-Tholin
Louise Brunkwall
Peter Nilsson
Gunnar Engström
Bo Hedblad
Nadine Bouby
Ronan Roussel
Lise Bankir
William Clark
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