Post on 29-Dec-2015
ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING
Lidder S1,2,3, Hunt J1,2, Omar S1,2, Webb A1,2
1King's College London, London, UK
2Guy's and St Thomas' NHS Foundation Trust, London, UK 3Barts and The London NHS Trust, London, UK
Systolic BP
-1 0 1 2 3 4 5 6
-10
-5
0
5
10
24
ControlBeetroot Juice
‡‡
†††
‡‡‡
‡ ‡
‡‡
Time (h)
B
P (
mm
Hg
)
Webb A. et al., Hypertension 2008;51:1-7
(23 mmol NO3-)
Hypothesis
• Provision of dietary nitrate may enhance glucose handling
Aim• To establish whether ingestion of a dietary
nitrate load improves glucose handling as shown by pl. glucose response to 75 g GTT
Study criteria
• Healthy subjects aged 18-45 years• BMI between 18 and 40 kg/m2
• Normotensive• Not taking systemic medication other than OCP
Baseline data
Subjects (n) 8
Male 4
Female 4
Age (years) 26.5±2.5
Weight (kg) 68.8±3.0
Height (cm) 173±0.04
BMI 22.9±0.8
Individual visit
• Double blind randomised placebo controlled cross-over design•KNO3 v KCl (both 24 mmol, capsules) +Gaviscon
•NO3- (24 mmol) ≈ 500 ml beetroot juice*
*Webb A. et al., Hypertension 2008;51:1-7
Effect of dietary nitrate on plasma NO3
-, NO2- & exhaled NO
NO3-
-1 0 1 250
100
150NitrateChloride
***
***
******
*** ***†††
500
1000
1500
2000
2500
3000
Time (h)
pla
sm
a [
nit
rate
] m
ol/
L
NO2-
-1 0 1 20
50
100
150
NitrateChloride
*** ***
***
***
***†††
300
600
900
1200
Time (h)
pla
sm
a [
nit
rite
] n
mo
l/L
NO
-2 -1 0 1 2 320
30
40
50
60
NitrateChloride
* *
**
†††
Time (h)
NO
(p
pb
)
Effect of dietary nitrate on plasma glucose & insulin during GTT (n=8)
Effect of dietary nitrate on plasma glucose & insulin during GTT (n=8)
Effect of dietary nitrate on BP
New hypothesis
• Association between glucose response + BP response to nitrate;
• on exposure to nitrate, subjects may either:• ‘respond’ = ↓ glucose• ‘reactors’ = ↑ glucose
• & this determines the BP response to nitrate
New study – 20 participants
Aim: • To prospectively determine whether there is an association between the glucose response and the BP response to nitrate
• Similar protocol,
• Responders or reactors: >5% Δ AUCglucose, KNO3 v KCl • KNO3 (8 mmol) ≈ 3-4 portions of green leafy veg
Primary outcome: • Difference in change in BP with nitrate, between nitrate reactors and responders (glucose)
Responders Reactors
Responders Reactors
Responders Reactors
Responders Reactors
Responders Reactors
Responders Reactors
Responders v Reactors
Responders v Reactors
Summary & Conclusions
• BP ↓ by nitrate in reactors• BP ↑ by nitrate in responders
• Responders have higher glucose curves in control: ↓ by nitrate (but BP ↑)
• Reactors have higher insulin curves with nitrate than responders– may be mechanism for vasodilatation and ↓BP
AcknowledgmentsAndrew WebbJoanne HuntSami OmarTony MarinakiLynette FairbanksGabriella PassacqualeKenneth ConnellHenry FokGanesh ArunachalamSikder Zubair RahimBenyu JiangSally BrettKaren McNeillAlbert FerroPhil ChowienczykClinical Research Facility nurses KCL BHF Centre
Baseline data
Subjects (n) 20
Male 9
Female 11
Age (years) 26.2±1.36
Weight (kg) 70.5±3.61
Height (cm) 174±0.03
BMI 23.1±0.63
Baseline data - Responders
Subjects (n) 12
Male 7
Female 5
Age (years) 27.4±1.78
Weight (kg) 73.8±4.92
Height (cm) 176±0.03
BMI 23.5±0.84
Baseline data - Reactors
Subjects (n) 8
Male 2
Female 6
Age (years) 24.3±2.06
Weight (kg) 65.5±5.04
Height (cm) 170±0.05
BMI 22.5±0.96
Baseline data – Responders >5% Δ AUCglucose
Subjects (n) 10
Male 6
Female 4
Age (years) 27.4±2.14
Weight (kg) 74.6±5.73
Height (cm) 178±0.03
BMI 23.3±1.00
Baseline data - Reactors >5% Δ AUCglucose
Subjects (n) 6
Male 2
Female 4
Age (years) 26.0±2.34
Weight (kg) 66.7±6.48
Height (cm) 172±0.05
BMI 22.2±1.27
Glucose
Insulin
C-peptide
Mean baseline SBP
Green leafy veg + diabetes• increasing consumption of green leafy
vegetables by one and a half UK portions a day (121.9g) could result in 14% reduction in the incidence of type 2 diabetes
• (Carter P. et al., BMJ 2010;341:c4229)
Responders v Reactors
Responders v Reactors
Comparison of control glucose curves
non-responders removed
-1.0 -0.5 0.0 0.5 1.0 1.5 2.0-15
-10
-5
0
5
RespondersReactors
††††
Time (h)
S
BP
(m
mH
g)