denis lairon, phd dr. lairon graduated with a phd in biochemistry
TRANSCRIPT
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
Effects of carbohydrates on Postprandial lipid metabolism
• Sugars
• Dietary fiber-rich foods
• Low-glycemic index foods
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
Effects of carbohydrates on Postprandial lipid metabolism
• Sugars
• Dietary fiber-rich foods
• Low-glycemic index foods
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
Postprandial lipemia in insulin-resistant patientsLow-and high-glycemic index foods
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)
**
A. Harbis,…, and D. Lairon ; Am J Clin Nutr, 2004
Postprandial lipemia in insulin-resistant patientsLow-and high-glycemic index foods
Triglycerides
Time (h)
Low GI-mealHigh GI-meal
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
A. Harbis,…, and D. Lairon ; Am J Clin Nutr, 2004
*
* * *
AUC > AUC
Early and late exacerbated increase inPostprandial ApoB48 after the high-GI by meal
Postprandial lipemia in insulin-resistant patientsLow-and high-glycemic index foods
Plasma ApoB48 (chylomicrons)
Low GI-mealHigh GI-meal
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
A. Harbis,…, and D. Lairon ; Am J Clin Nutr, 2004
Early exacerbated accumulation of VLDL particlesafter high-GI meal
Postprandial lipemia in insulin-resistant patientsLow-and high-glycemic index foods
TRL-ApoB100 (VLDL)
1.5
1.6
1.7
1.8
1.9
0 2 4 6
*
Time (h)
Low GI-mealHigh GI-meal
TRL
-Apo
B 100
mg /
ml
A. Harbis,…, and D. Lairon ; Am J Clin Nutr, 2004
Postprandial lipemia in insulin-resistant patientsLow-and high-glycemic index foods
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
A. Harbis,…, and D. Lairon ; Am J Clin Nutr, 2004
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