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ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3 , Hunt J 1,2 , Omar S 1,2 , Webb A 1,2 1 King's College London, London, UK 2 Guy's and St Thomas' NHS Foundation Trust, London, UK 3 Barts and The London NHS Trust, London, UK

ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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Page 1: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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

Page 2: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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-)

Page 3: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and
Page 4: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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

Page 5: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Study criteria

• Healthy subjects aged 18-45 years• BMI between 18 and 40 kg/m2

• Normotensive• Not taking systemic medication other than OCP

Page 6: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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

Page 7: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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

Page 8: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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

)

Page 9: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Effect of dietary nitrate on plasma glucose & insulin during GTT (n=8)

Page 10: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Effect of dietary nitrate on plasma glucose & insulin during GTT (n=8)

Page 11: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Effect of dietary nitrate on BP

Page 12: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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

Page 13: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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)

Page 14: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Responders Reactors

Page 15: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Responders Reactors

Page 16: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Responders Reactors

Page 17: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Responders Reactors

Page 18: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Responders Reactors

Page 19: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Responders Reactors

Page 20: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Responders v Reactors

Page 21: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Responders v Reactors

Page 22: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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

Page 23: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

AcknowledgmentsAndrew WebbJoanne HuntSami OmarTony MarinakiLynette FairbanksGabriella PassacqualeKenneth ConnellHenry FokGanesh ArunachalamSikder Zubair RahimBenyu JiangSally BrettKaren McNeillAlbert FerroPhil ChowienczykClinical Research Facility nurses KCL BHF Centre

Page 24: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and
Page 25: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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

Page 26: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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

Page 27: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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

Page 28: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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

Page 29: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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

Page 30: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Glucose

Page 31: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Insulin

Page 32: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

C-peptide

Page 33: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Mean baseline SBP

Page 34: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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)

Page 35: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Responders v Reactors

Page 36: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Responders v Reactors

Page 37: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

Comparison of control glucose curves

Page 38: ACUTE EFFECTS OF DIETARY NITRATE ON GLUCOSE HANDLING Lidder S 1,2,3, Hunt J 1,2, Omar S 1,2, Webb A 1,2 1 King's College London, London, UK 2 Guy's and

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)