Severe obesity is a congenital disease The team

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Severe obesity is a congenital diseaseThe team
Bariatric surgeons
Researchers

• Simon Biron
• Frederic S. Hould
• Stefane Lebel
• Simon Marceau
• Odette Lescelleur
• Laurent Biertho
• Fady Moustarah
• Picard Marceau

Katherine Cianflone expertise adipose
tissue Jessica Smith Marie-Claude Vohl expertise
genomic Frédéric Guénard
Bariatric Physician Stefan Brouw
Special Contribution John G. Kral, NY.
Laval University, Québec.
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Introduction
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Sturm R. Public Health 2007 121 495
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Introduction
Child obesity / parental weight
Whitaker KL. Am J Clin. Nutr 2010
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Severe obesity is a serious disease
Introduction

• CDCP predict that 1/3 children born in 2000 will
  be diabetic
• JAMA 2003 290 1884-1890
• Children (5yrs) intelligence inversely related to
  insulin resistance (IR) Rizzo T. NEJM 1991
  325 911-916
• Life style intervention not very efficient in
  curing obesity and diabetes
  Today Study 2012

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Publications
Introduction

• 1993 Newborns from operated mother less obese
  than sibling born before surgery
  Progress of obesity research 8 ed. Paris
• 2004 Children less obese
  Marceau et al. Obes. Surg. 14 318.
• 2006 Morphologic study larger cohort Kral
  et al Pediatric 118 1644.
• 2009 Metabolic study
  Smith et al J Clin. Endo Metab. 94 4275.

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SourceChildren from all mothers withchildren
born after surgery (n151)
Introduction
Study group n 133 mothers

• 183 children born after maternal surgery (AMS)
• 89 children born before maternal surgery
  (BMS)

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Goal
Introduction

• In the severely obese mother something is present
• before surgery, removed by surgery
• which prevents transmission of an accelerated
  obesity.

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Definition of obesityreference charts
Method

• BMI Percentile (NHANES 2000) overweight
  85
• obesity 95
• severe obesity 98
• BMI Z-score (CDC growth chart 2006) overweight
  2
• obesity 2.5
• severe obesity 3
• WC/HT ratio (AA Ped. 2006) obesity
  90
• Body Fat (NHANES III 2002) obesity
  30
• bioelectric impedance data

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Method
BPD
Duodenal Switch
Distal Gastrectomy
n 109
n 24
250 cm ?
250 cm ?
50 cm
100 cm
1984- June 1990
June 1990-2009
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Dietary habitNo significant changes between BMS
and AMS
Method
Questionnaire

• 1/3 Breast feeding same duration
• 78 no change in quantity of food
• 60 no change in quality of food

Dieting
78
60 same environment (BMSAMS)
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Source/morpho
The source U Laval Mother-Child Obesity Study
Among 2287 operated women
151 mothers with AMS
Mothers
133 (88)
183 AMS
89 BMS
Offspring
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Effect of surgery on mothers (n133)
mother/morpho
16 years postop
Age 26 to 43

BMI
36

52
Prevalence of obesity

77
Prevalence of severe obesity


13
42
FBS
TGTC/HDL
plt0.0001
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Repercussion on offspring
Children/morpho
BMS n89 vs. AMS n183
Age difference 15.8 5.8 vs. 8.3 4.2 yrs
p
BMI
51
0.0005
Z-score
56
0.003
18
WC/HT gt90
0.05
Obesity (BMIgt30)
45
0.04
Severe obesity (BMIgt35)
67
0.0001
The more severe the greater the beneficial effect
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Growth trajectoryduring childhood
Children/morpho
Difference between BMS and AMS

• BMI-Zscore trajectory 3 times slower/yr in AMS
• (Fig 2) (p0.036)
• Abdominal obesity trajectory 5 times slower/yr in
  AMS
• (Fig 2) (plt0.001)

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Children/morpho
BMS AMS
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Children/morpho
BMS AMS
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Metabolic study
Source/metabo
All mothers with both AMS and BMS children
31/42
mothers
46
46
children
BMS
AMS

mothers
10
10
17
14
BMS
AMS
children
63
60
matched for age sex
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Metabolic studyrelation between mother/child
Metabo/method

• Blood lipids
• Glycemia
• Metabolic hormone
• Gut function
• Adipose Tissue
• Insulin Homa-IR

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Metabolic change in mothers (n51) after surgery
Mother/metabo
Before surgery
At time of study
Change
Age yrs BMI kg/m2

29.2
43

30.6
46.5
15

FBG mmol/l
5.5
4.7
81

Insulin µU/ml
59.3
11.5
2.4
82

Homa-IR ratio
13.7

50
TG mmol/l
1.8
0.9
35

TC mmol/l
5.2
3.4
50

LDL mmol/l
3.2
1.6

47
TC/HDL mmol/l
4.7
2.5

HDL mmol/l
17
1.2
1.4
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plt0.0001
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Metabolic repercussion on offspringBMS (n63)
vs. AMS (n60)
Children/metabo
change
p
FBG mmol/l 3 0.009 Insulin µU/ml 30 0.005 Homa-I
R ratio 31 0.008 TG mmol/l 22 0.46 TC/HDL
ratio 13 0.02 HDL mmol/l 11 0.02 SBP mm
Hg 13 0.001 DBP mm Hg 19 0.0007
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Effect on lipid is for severe obesity
Children/metabo
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BirthweightBMS vs. AMS
Children/metabo
BMS n54
AMS n57
p

• Birthlength cm 50 49 ns
• Birthweight kg 3.3 2.9 0.003
• Macrosomia (gt4kg) 8 1 0.03
• Low birthweight (lt2.5kg) 6 10 ns

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Gender difference
Morpho Metabo

• Initially prevalence of severe obesity and
  dyslipidemia greater in boys.
• Improvement greater in boys
• Improvement in insulin resistance the same for
  both sexes

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After pubertyBMS n39 vs. AMS n16Age 17.91.9
vs. 15.81.8 yrs
Children/metabo
change
p
Zscore mean 54 0.08 BMI 98 tile 71 0.05 WC
gt90 50 ns FBS mmol/l 9 0.02 TC/HDL
mmol/l 21 0.03 Homa-IR ratio 39 0.16
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Insulin Resistancedecrease more than bodyweight
(glucose remains stable)
Insulin key role
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Insulinstrong mother/child correlation
Insulin key role

• BMS r 0,71 p0.04
• AMS r 0.45 plt0.001

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Insulin key role
Progression of Insulin
BMS AMS
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Insulin key role
BMS AMS
If blood glucose 4g/l insulin level is half in
AMS (6.5 vs. 12 µU/ml)
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Predictor of obesity (Pearson corr)Homa-IR but
not glucoseAMS children
IR Key role
Glucose
Homa-IR
n r p n r p
BMI 59 0.05 0.73 51 0.67 0.0001
Z-Score 59 0.17 0.19 52 0.45 0.0009
WC/HT 59 -0.01 0.94 52 0.40 0.0041
tissu fat 25 0.03 0.89 23 0.76 0.0001
TG mmol/l 58 0.08 0.54 52 0.40 0.003
CTO/HDL ratio 58 0.04 0.74 52 0.26 0.06
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Inflammatory factor (CRP)varies with IR
CRP follows insulin
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To blame IR is no surprise
Comment 1

• Characteristic of obese children IR 72
• Impaired gluc tolerance 3 (Druet
  2006)
• Insulin level in utero predictor of future
  obesity (Metzer 1990)
• Insulin level in Pigma Indian Children predictor
  of future obesity (Odeleve 1997)
• The role of insulin in the mechanism of weight
  stability is well known
• Astrup 90
• Tremblay 95
• Levine 99

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Mechanism of transmissionof gluco regulators
Comment 2
Environmental factor methylation of
genes preventing gene expression
Reversible

• Maternal weight loss surgery impacts gene
  methylation in offspring and regulates gluco
  regulator genes

Guénard F, Vohl MC. al. In preparation
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Insulin Surgery increases insulin sensitivity
even above normal
Comment 3 advantage of BPD
After meal
Fasting
nmol/l/180m
pmol/l
Plt0.005

Plt0.001
89.4 10.9
33.4 4
29,7 5

26.3 3.1
17.8 4
13.2 1.9
BEFORE
AFTER
BEFORE
AFTER
n non-obese 13 obese before 16 obese after
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Sarson, Int J Obes 81
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Another advantage of BPD
Comment 4

• Decreases fat absorption

High fat diet during pregnancy is detrimental
Grove KL. News Med Net abstr 2008 Unger 2010
Lipotoxicity Sullivan EL. 2011
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Weakness
Comment 5

• It is not a longitudinal study
• but
• Environmental factor only subjective evaluation
  but

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Conclusion
Severe obesity is a congenital disease
Transmission of both
Regular genetic characters plus Maternal
insulin resistance

• Which explains the vicious circle
• Preventive measures to improve mother insulin
  sensitivity

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