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

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***

******

*** ***†††

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)