Denis Lairon, PhD Dr. Lairon graduated with a PhD in biochemistry

Denis Lairon, PhD

Dr. Lairon graduated with a PhD in biochemistry, and served as Research Director at Inserm (National Institute of Health and Medical Research) in 1999. Since 1997 Dr. Lairon has been Director of the Joint Research Unit INSERM 476 / INRA 1260, at the Faculty of Medicine of Marseille. He is the co-author of 140 original papers and 70 reviews and book chapters; was a member of the Editorial Board of the British Journal of Nutrition, 1997-2002; chairman of the 2nd Congress of Nutrition in Marseille in 2005, and chairman of the Scientific committee of the 10th FENS European Nutrition Congress to be held in Paris in Summer, 2007.

Carbohydrate Glycemic Indexlipid metabolism and

cardiovascular risk

Denis LaironMarseille, France

UMR 476-INSERM /1260 INRAHuman Nutrition and Lipids

Glycemic index of foods

Glucose 100

French baguette, white bread 95Corn flakes 80White wheat bread 71Wholemeal wheat bread 69Muesli 56

Wholemeal rye bread 55Brown rice 55White rice 50Oat bran bread 47White durum spagetti 47

Wholemeal durum spagetti 43Baked beans 40Chickpeas 36Lentils 33Wholewheat kernel 30

Time (h)

Glucose (g/l)

High-carbohydrate diets(> 60 % E) (Parks, 2001)

increase fasting triglycerides and LDL cholesterol

Dietary carbohydrate and lipid metabolism (1)

High-fructose/sucrose diets promote hypertriglyceridemia

Low-GI starchy diets improve lipid metabolic profile(Jenkins et al., 1987; Wolever et al., 1992; Frost et al., 1996; Liu et al., 2001 Jenkins et al., 2002; Bouché et al., 2003; Wolever & Mehling, 2003)

Recommended diets : Carbohydrate (mostly starch) = 50-55 % E

Hyperinsulinemia and insulin-resistance are associated with :

fasting hypertriglyceridemiaexagerated postprandial lipemia

(Lewis et al., 1990 ; Jeppesen et al., 1995 ; Curtin et al., 1996 ; Couillard et al., 1998 ; Mekki et al., 1999 ; Guerci et al., 2000 ; Kim et al., 2001 ; Mamo et al., 2001)

Dietary carbohydrate and lipid metabolism (2)

Postprandial lipemia

Plasma accumulation of triglyceride-rich lipoproteins

Atherosclerosis

Dietary fat

Mixed diets, lipid metabolism and CVD risk

Time (h)

Triglycerides

INSULIN

Hyperglycemia

Genes/enzymes involved in lipid synthesis and

metabolism

Dietary carbohydrate

Time (h)

Glucose

Time (h)

Insulin

Excessinsulin

Intestine

Chylomicron

Chylomicronremnant

Chylomicronremnant

Hepaticlipase

Lipoprotein lipase

B48 C-III

E

C-III

E

C-II

I

E

SR-BI

MTPFABP

A-IV

B48

B48

A-IV

NEFA

Key pathways in lipoprotein metabolism

SR-BIRemnant receptor

LDL receptor

Lipoproteinlipase

Hepaticlipase

LDL

HDL

VLDL

Cells

Cholesterol pool

HDL receptorABC receptor

LDL receptorScavenger receptor

A-1

A-I1

E

C-III

E IDLC-III

B100

B100

B100

CETPPLTP

Adipose

NEFA

NEFA

LIVER

Fairnaru… Kaplan, Isr., Med. Sci., 1994

Chol

este

rol (

mm

ol/L

)Tr

igly

ceri

des

(mm

ol/L

)

1.0

1.5

2.0

2.5

Whole plasma

Chylomicronplasma

A

B

7 8 10 12 14 16 18 20 22 24 3 7Time of day (h)

4.2

4.6

5.0

Postprandial lipemia

Risk factors for cardiovascular disease

• Hypercholesterolemia, LDL- cholesterol

• Hypertriglyceridemia, TRL- remnants

• Obesity, insulin-resistance

• Elevated pro-thrombotic factors (PAI- 1, F-VII…)

• Hypertension

Effects of carbohydrates on Postprandial lipid metabolism

• Sugars

• Dietary fiber-rich foods

• Low-glycemic index foods

Sugars and postprandial lipemiaSugars and postprandial lipemia

From Cohen, 1988 ; Jeppesen 1995, Shushehbora, 1998 .

Serum triglyceride concentrations in 18 normolipidemic subjects aftermeal containing 100g glucose + 40g fat ( ) or 40g fat alone ( )

Seru

mtr

igly

c er i

de

conc

entr

ati o

n s ( m

g /d L

)

0 2 4 6 85075

100

125

150

Glucose : pp lipemia

Saccharose, fructose : pp lipemia 1

2

3

8a 10a 12n 2p 4p 6p

1

2

3

8a 10a 12n 2p 4p 6pSe

rum

trig

lyc e

r ide

con

c en t

r at i

ons

( g/ L

)

Fructose > Sucrose > Glucose exacerbatesPostprandial lipemia


• Sugars



Wheat fiber (WF)

Oat bran (OB) Control (C)

Wheat germ (WG)

Rice bran (RB)

1.51.31.10.90.70.50.3

0.00.1

0 1 2 3 4 5 6 7

∆Pl

asm

a tr

igly

céri

des

(mm

ol/L

)

Time (h)

A

∆Pl

asm

a tr

igly

céri

de

area

(mm

ol/L

).h 4

3

2

1

0

B*

**

Control Oat bran

Rice bran

Wheatfiber

Wheatgerm

4.12 3.12 3.67 2.74 3.24

Fibres and postprandial lipemiaFibres and postprandial lipemia

Cara… Lairon, Am J Clin Nutr, 1992

- 0.5

- 0.4

- 0.3

- 0.2

- 0.1

0.0

∆Pl

asm

a ch

oles

tero

l (m

mol

/L)

0 1 2 3 5 6 74

Wheat fiber (WF) Wheat germ (WG)

control (C)

OB

OBWG OB

WF

OBWFWG OB

Oat bran (OB) Rice bran (RB)

RB

Time (h)∆

Plas

ma

chol

este

rol

area

(mm

ol.L

/h)

- 4

- 3

- 2

- 1

0

Control Oatbran

Ricebran

Wheatfiber

Wheatgerm

0.86 2.19 0.82 1.62 1.68

Cara … Lairon, Am J Clin Nutr, 1992

Fibres and postprandial lipemiaFibres and postprandial lipemia

Dietray fiber lower Postprandial lipemia


• Sugars



Dietary starch sources might influence

postprandial lipid metabolism through insulin action

Concept

1. a study in healthy subjects (n= 10).Harbis A., …, and D. Lairon, Diabetes, 2001

Study design

Aim : to modulate insulin responses to evaluateeffects on postprandial lipemia and lipoproteins

• euglycemic-hyperinsulinic clamp surimposed to a no-carbohydrate meal

• 4 test-meals inducing different glycemic responses

test-meals (iso-lipidic et iso-proteic) : White wheat bread (GI = 100)

Pasta (GI = 70-75)

Broad beans (GI = 35)

No carbohydrate

90g carbohydrate (or no) 40g fat : olive oil33g protein

Postprandial glycemia

Time (hours)0 2 4 6

4

5

6

7

mm

ol/L

White breadPastaBroad beansNo-carb

Kinetics

mm

ol.h

/L-2-1012345

AUCs

xx

yy

White bread

a, b / x, y : Statistically différent (p<0,05)

AUC 0-2hAUC 0-6h

a

b

a

b

Pasta Broad beans No-carb

Postprandial insulinemia

White bread

Broad beansNo-carb

Kinetics

mU

/L

0

10

20

30

40

0 2 4 6

Time (hours)p<0,05

Pasta

** *

mU

.h/L

a, b, c / x, y, zStatistically différent (p<0,05)

AUCs

y

z

y

0

20

40

60

80

White bread Pasta Broad beans

x

No-carb

AUC 0-3ha

a, bb, c

c

AUC 0-6h

Following a mixed meal,

rise in insulin concentration is proportional to the glycemic index of the carbohydrate source.

Postprandial triglyceridemia

Highest GIs are associated with trend to

delayed triglyceridemia

∆TG

( mm

ol/L

)

GI 35No-carb

GI 100GI 70

-0,2

0,0

0,2

0,4

0,6

0,8

1,0

0 1 2 3 4 5 6Time (hours)

Kinetics

Plasma chylomicrons ApoB48

Time (hours) p<0.05

GI 100

Insulin (mU.h/L)Apo

B48

(µg

.h/ m

l)

r2 = 0,700P = 0,0001

0.00.10.20.30.40.50.60.7

20 40 60 80 100

Harbis…Lairon, Diabetes, 2001, 50:462-469

0 2 3 4 6

0,00

0,04

0,08

0,12 **

GI 35No Carb

GI 70

Apo

B48

(µg /

ml)

higher glycemic index, higher postprandial insulinemia,higher (late) accumulation of intestinally-derived lipoproteins

Harbis…Lairon, Diabetes, 2001, 50:462-469

Hyperinsulinism per se alters postprandial lipid metabolism :

• exarcerbates postprandial lipemia

• delays chylomicron accumulation

* * * * *

Insulin*

****

100

20406080

*120

mU

/L

*

Chylomicrons *

0,0

0,4

0,8

1,2

0 1 2 3 4 5 6

TG

mm

ol/L

*

0 1 2 3 4 5 6

VLDL *

Time (hours)

0.0

0.4

0.8

1.2

TG

mm

ol/L

No-carbohydrate meal

Hyper-insulinic clamp inhealthy subjects

Dietary digestible carbohydrate sources might influence

postprandial lipid metabolism through insulin action

Concept

2. a study in obese insulin-resistant subjects (n= 9).A. Harbis,…, and D. Lairon ; Am J Clin Nutr, 2004

Postprandial lipemia in insulin-resistant patientslow-and high-glycemic index foods

- Patients n=9, women- Age : 35 (25-45y)- Obesity : BMI : 36.4 ± 5.4- Insulin-resistance HOMA score : 3.04 - Dietary intake 2328 ± 490 kcal/d

western-type diet

-Glycemia : 5.6 ± 0.2mmol/L-Insulinemia : 83.1 ± 9.8 pmol/L-Triglyceridemia : 1.1 ± 0.7 mmol/L-Cholesterolemia : 5.5 ± 0.4 mmol/L

Test meals- Fat : 29g - Protein : 16-24 g- Carbohydrate : 94g - high SAG (17g/100) : est. GI < 45

- low SAG (2g/100) : est.GI ≥ 75

Transient exarcerbated increase in postprandial glycemia after the high-GI meal

Postprandial lipemia in insulin-resistant patientsLow-and high-glycemic index foods

Glycemia9.00

4.00

5.00

6.00

7.00

8.00

0 1 2 3 4 5 6

Glu

cose

mm

ol/L

TIME (h)

Low GI-meal

High GI-meal

*

A. Harbis,…, and D. Lairon ; Am J Clin Nutr, 2004

Early and overall exacerbated increasein postprandial insulinemia after the high-GI meal


Insulinemia

0 1 2 3 4 5 60

139

278

417

556

694

833

**

972111112501389

0-2h 0-6h

Low GI-mealHigh GI-meal

Insu

lin (pm

mol/L

)

0139278417556694833

Insu

lin I

AUC

(pmol.h

/L)

Time (h)

**



Triglycerides

Time (h)


1

1.4

1.8

2.2

0 1 2 3 4 5 6

Triglyce

ride

s mmol/L

Exacerbated postprandial lipemia after the high-GI meal


*

* * *

AUC > AUC

Early and late exacerbated increase inPostprandial ApoB48 after the high-GI by meal


Plasma ApoB48 (chylomicrons)


0

5

10

15

20

25 *

Apo

B48

IAU

C 0-

6h m

g.h/

mL

0

2

4

6

8

0 1 2 3 4 5 6Time (h)

*

Plas

ma

Apo

B48

mg/

mL


Early exacerbated accumulation of VLDL particlesafter high-GI meal


TRL-ApoB100 (VLDL)

1.5

1.6

1.7

1.8

1.9

0 2 4 6

*

Time (h)


TRL

-Apo

B 100

mg /

ml



Conclusion

In obese patients with insulin-resistance but normal triglyceridemia

A high-GI, fat meal compared to a low-GI, fat meal :

Increases postprandial glycemia and insulinemia

Increases the number of chylomicron particles (ApoB48) postprandiallyIncreases the number of VLDL particles (ApoB100) postprandially


High-GI foods exarcerbate/delay posprandial lipemia and lipoproteins :

Conclusion : Glycemic index of foods and lipid metabolism

• in both subjects and patients : a previous high-GI meal will exacerbate fasting and postprandial lipemia at the next meal.

• in insulin-resistant patients

• postprandial effects of food GIs can link glycemic load and reported cardiovascular risk during surveys (Liu et al., 2000).

• in healthy subjects

Pasta is a suitable source of starchwith moderate / low GI

to minimize impact on lipid metabolism and related cardiovascular risk

Conclusion: Pasta and lipid metabolism

Further reduction of pasta GI is acknowledged (soluble fiber content, minimal « al dente » cooking,…)

UMR 476 INSERM/1260 INRA Human nutrition and lipids

Denis LAIRON, Ph D

Louis CARA, Ph D Nadia MEKKI, PhD

Monique CHARBONNIER, Ph D Barbara PLAY, PhD student

Catherine DEFOORT, PhD Henri PORTUGAL, Ph D

Christophe DUBOIS, Ph D Denis RACCAH, MD, PhD

Amandine HARBIS, PhD Michèle SENFT

Dominique JOURDHEUIL-RAHMANI, PhD Bernard VIALETTES, MD, PhD

Good for health

Denis Lairon, PhD Dr. Lairon graduated with a PhD in biochemistry

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