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Severe obesity is a congenital disease The team

Bariatric surgeons. Researchers. Severe obesity is a congenital disease The team. Katherine Cianflone expertise adipose tissue Jessica Smith Marie-Claude Vohl expertise genomic Frédéric Guénard. Simon Biron Frederic S. Hould Stefane Lebel Simon Marceau Odette Lescelleur

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Severe obesity is a congenital disease The team

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  1. Bariatric surgeons Researchers Severe obesity is a congenital diseaseThe team Katherine Cianflone expertise adipose tissue Jessica Smith Marie-Claude Vohl expertise genomic Frédéric Guénard Simon Biron Frederic S. Hould Stefane Lebel Simon Marceau Odette Lescelleur Laurent Biertho Fady Moustarah Picard Marceau Bariatric Physician Stefan Brouw Special Contribution John G. Kral, NY. Laval University, Québec. CABPS/ACMCB Toronto 2012

  2. Introduction CABPS/ACMCB Toronto 2012 Sturm R.: Public Health 2007; 121: 495

  3. Introduction Child obesity / parental weight Whitaker KL. Am J Clin. Nutr 2010

  4. Introduction Severe obesity is a serious disease • 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 CABPS/ACMCB Toronto 2012

  5. Introduction Publications • 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. CABPS/ACMCB Toronto 2012

  6. Introduction SourceChildren from all mothers withchildren born after surgery (n:151) • 183children born after maternal surgery (AMS) • 89children born before maternal surgery (BMS) Study group: n: 133 mothers

  7. Introduction Goal • In the severely obese mother something is present • before surgery, removed by surgery • which prevents transmission of an accelerated obesity. CABPS/ACMCB Toronto 2012

  8. Method Definition of obesityreference charts • 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 CABPS/ACMCB Toronto 2012

  9. Method BPD Duodenal Switch Distal Gastrectomy n: 109 n: 24 250 cm  250 cm  50 cm 100 cm 1984- June 1990 June 1990-2009 CABPS/ACMCB Toronto 2012

  10. Method Dietary habitNo significant changes between BMS and AMS • 1/3 Breast feeding same duration • 78% no change in quantity of food • 60% no change in quality of food Questionnaire Dieting 78% 60% same environment (BMS&AMS) CABPS/ACMCB Toronto 2012

  11. Source/morpho The source U Laval Mother-Child Obesity Study Among 2287 operated women 151 mothers with AMS Mothers 133 (88%) 89 BMS 183 AMS Offspring CABPS/ACMCB Toronto 2012

  12. mother/morpho Effect of surgery on mothers(n:133) 16 years postop Age 26 to 43 * BMI 36% * 52% Prevalence of obesity * 77% Prevalence of severe obesity * * 13% 42% TG&TC/HDL FBS *p<0.0001 CABPS/ACMCB Toronto 2012

  13. Children/morpho Repercussion on offspring BMS n:89 vs. AMS n:183 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 >90% 0.05 Obesity (BMI>30) 45% 0.04 Severe obesity (BMI>35) 67% 0.0001 The more severe the greater the beneficial effect CABPS/ACMCB Toronto 2012

  14. Children/morpho Growth trajectoryduring childhood • BMI-Zscore trajectory 3 times slower/yr in AMS • (Fig 2) (p=0.036) • Abdominal obesity trajectory 5 times slower/yr in AMS • (Fig 2) (p<0.001) Difference between BMS and AMS CABPS/ACMCB Toronto 2012

  15. Children/morpho BMS: AMS: CABPS/ACMCB Toronto 2012

  16. Children/morpho BMS: AMS: CABPS/ACMCB Toronto 2012

  17. Source/metabo Metabolic study All mothers with both: AMS and BMS children 31/42 mothers 46 46 children BMS AMS + 10 10 mothers 17 14 BMS * AMS * children 63 60 *matched for age & sex CABPS/ACMCB Toronto 2012

  18. Metabo/method Metabolic studyrelation between mother/child • Blood lipids • Glycemia • Metabolic hormone • Gut function • Adipose Tissue • Insulin Homa-IR CABPS/ACMCB Toronto 2012

  19. Mother/metabo Metabolic change in mothers(n:51)after surgery Before surgery At time of study Change % Ageyrs 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 1.6 3.2 * 47 TC/HDL mmol/l 4.7 2.5 * HDL mmol/l 17 1.2 1.4 CABPS/ACMCB Toronto 2012 *p<0.0001

  20. Children/metabo Metabolic repercussion on offspringBMS (n:63) vs. AMS (n:60) % change p FBG mmol/l 3 0.009 Insulin µU/ml 30 0.005 Homa-IR ratio 31 0.008 TG mmol/l 22 0.46 TC/HDL ratio 13 0.02 HDL mmol/l 11 0.02 SBP mmHg 13 0.001 DBP mmHg 19 0.0007 CABPS/ACMCB Toronto 2012

  21. Children/metabo Effect on lipid is for severe obesity CABPS/ACMCB Toronto 2012

  22. Children/metabo BirthweightBMS vs. AMS • Birthlength cm 50 49 ns • Birthweight kg 3.3 2.9 0.003 • Macrosomia% (>4kg) 8 1 0.03 • Low birthweight%(<2.5kg) 6 10 ns BMS n:54 AMS n:57 p CABPS/ACMCB Toronto 2012

  23. Morpho & Metabo Gender difference • Initially prevalence of severe obesity and dyslipidemia greater in boys. • Improvement greater in boys • Improvement in insulin resistance the same for both sexes CABPS/ACMCB Toronto 2012

  24. Children/metabo After pubertyBMS n:39vs.AMSn:16Age: 17.9±1.9 vs. 15.8±1.8 yrs % change p Zscore mean 54 0.08 BMI ≥98 %tile 71 0.05 WC >90% 50 ns FBS mmol/l 9 0.02 TC/HDL mmol/l 21 0.03 Homa-IR ratio 39 0.16 CABPS/ACMCB Toronto 2012

  25. Insulin: key role Insulin Resistancedecrease more than bodyweight (glucose remains stable) CABPS/ACMCB Toronto 2012

  26. Insulin: key role Insulinstrong mother/child correlation • BMS r: 0,71 p=0.04 • AMS r: 0.45 p<0.001 CABPS/ACMCB Toronto 2012

  27. Insulin: key role Progression of Insulin BMS: AMS: CABPS/ACMCB Toronto 2012

  28. Insulin: key role BMS: AMS: If blood glucose 4g/l insulin level is half in AMS (6.5 vs. 12 µU/ml) CABPS/ACMCB Toronto 2012

  29. IR= Key role Predictor of obesity(Pearson corr)Homa-IR but not glucoseAMS children Glucose Homa-IR

  30. CRP follows insulin Inflammatory factor (CRP)varies with IR CABPS/ACMCB Toronto 2012

  31. Comment 1 To blame IR is no surprise • 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 CABPS/ACMCB Toronto 2012

  32. Comment 2 Mechanism of transmissionof gluco regulators • Maternal weight loss surgery impacts gene methylation in offspring and regulates gluco regulator genes Environmental factor = methylation of genes preventing gene expression Reversible Guénard F, Vohl MC.& al. In preparation CABPS/ACMCB Toronto 2012

  33. Comment 3 advantage of BPD Insulin Surgery increases insulin sensitivity even above normal After meal Fasting nmol/l/180m pmol/l *** ** P<0.005 *** P<0.001 89.4 ± 10.9 33.4 ± 4 29,7 ± 5 ** 17.8 ± 4 26.3 ± 3.1 13.2 ± 1.9 BEFORE AFTER BEFORE AFTER n: non-obese: 13; obese before: 16; obese after: 38 Sarson, Int J Obes 81 CABPS/ACMCB Toronto 2012

  34. Comment 4 Another advantage of BPD • Decreases fat absorption High fat diet during pregnancy is detrimental Grove KL. News Med Net abstr 2008 Unger 2010 Lipotoxicity Sullivan EL. 2011 CABPS/ACMCB Toronto 2012

  35. Comment 5 Weakness • It is not a longitudinal study • but… • “Environmental factor” only subjective evaluation but… CABPS/ACMCB Toronto 2012

  36. Conclusion Severe obesity is a congenital disease • Which explains the vicious circle • Preventive measures: to improve mother insulin sensitivity Transmission of both Regular genetic characters plus Maternal insulin resistance CABPS/ACMCB Toronto 2012

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