1. MALABSORPTIVE BARIATRIC SURGERY in Low BMI Korean Patients Ji Yeon Park Soonchunhyang University Seoul Hospital, Korea

2. Body weight / Height 2 The most practical measure of a person’s adiposity BMI (kg/m 2 )WHO classification of weight status 25 ~ 29.9Overweight 30 ~ 34.9Mildly Obese (Class I obesity) 35 ~ 39.9Moderately obese (Class II obesity) 40 ~ 49.9Severely or extremely obese (Class III obesity) >50Super obese (Class IV obesity)

3. NIH Consensus statement 1991 risk/benefit ratio  Decision based on a prudent evaluation of the risk/benefit ratio Era of open surgery A very few surgical options

4. Roux-en-Y gastric bypass (RYGB)Laparoscopic adjustable gastric banding (LAGB) Biliopancreatic diversion (BPD)Biliopancreatic diversion with duodenal switch (BPD/DS) Sleeve gastrectomy (SG)

5. Dixon et al. Lancet 2012; 379: 2300-11

6. Long-term, prospective, controlled trial 4047 obese subjects surgery group (n=2010) vs. control group (n=2037) Recruitment : Sep 1987 ~ Jan 2001 BMI : Men ≥ 38, women ≥ 34 Gastric bypass (13%), banding (19%) & vertical banded gastroplasty (68%) Follow-up: 12 ~ 25 years

7. The SOS intervention study

8. Adjusted hazard ratio 0.17 (0.13 - 0.21) Carlsson et al. N Engl J Med 2012;367:695-704

9. BARIATRIC SURGERY Lower the BMI & Body weight METABOLIC SURGERY Reduce HbA1c & medications

10. NIDDM 121 / 146 (82.9%) IGT 150 / 152 (98.7%)  Euglycemia

11. Mingrone et al. N Engl J Med 2012;366:1577-85. Single-center, nonblinded, randomized, controlled trial Medical therapy vs. BPD vs. RYGB 60 pts Age : 30 ~ 60 years BMI ≥ 35 DM > 5 years HbA1c ≥ 7.0%

12. Outcomes at 2 years Mingrone et al. N Engl J Med 2012;366:1577-85.

13. Difference in the rate of T2DM remission At 2 years Medical therapy RYGBBPDP-value Diabetes remission015 (75%)19 (95%)<0.001 Relative risk 7.5 (95% CI, 1.97 - 28.61) 9.5 (95% CI, 2.54 - 35.51) <0.001 Time to normalization (months) 10±24 ± 10.01 Mingrone et al. N Engl J Med 2012;366:1577-85.

14. Schauer et al. N Engl J Med 2012;366:1567-76 Randomized, non-blinded, single-center trial intensive medical therapy vs. RYGB vs. SG 150 pts age 20 ~ 60 years type 2 diabetes HbA1c >7.0% BMI 27 ~ 43

15. At 12 months Schauer et al. N Engl J Med 2012;366:1567-76

16. Changes in Diabetes Control Over 3 Years Schauer et al. N Engl J Med 2014;370:2002-13 Predictors of HbA1c <6.5% at 36 months Reduction in BMI (OR 1.33; 95% CI 1.15 – 1.56) DM duration < 8 years (OR 3.3; 95% CI 1.2 – 9.1)

17. Evidence 1 Rapid Kinetics of diabetic improvement after surgery Evidence 2 Greater glycemic improvement than with equivalent weight loss from other means Evidence 3 hyperinsulinemic hypoglycemia Weight independent anti-diabetic effects of malabsorptive procedures: evidences

18. Evidence 1. Rapid improvement in insuline resistance Wickremesekera et al. Obesity Surgery, 2005, 15, 474-481 The change in insulin resistance occur within 6 days of the surgery, before any appreciable weight loss has occurred!

19. Laferrere et al. J Clin Endocrinol Metab, July 2008, 93(7):2479–2485

20. Evidence 3. Hyperinsulinemic hypoglycemia Service et al. N Engl J Med 2005;353:249-54 RYGB  Long lasting stimulation of β-cell mass and/or function..

21. Better glycemic control Improved insulin resistance Weight loss restriction malabsorption Brain-Gut Axis Entero-Insular Axis

22. The starvation hypothesis The ghrelin hypothesis The hindgut stimulation hypothesis The foregut exclusion hypothesis

23. Acute restriction of energy intake  transiently improves glycemia… Buchwald et al. JAMA. 2004;292(14):1724-1737

24. Gastric bypass is associated with markedly suppressed ghrelin levels, possibly contributing to the weight-reducing effect & improvement in glucose tolerance of the procedure. Cummings et al. N Engl J Med 2002;346:1623-30 Diet induced weight loss

25. Mason et al. Obesity Surgery, 15, 459-461 Rapid & early delivery of undigested nutrients to the distal ileum Stimulation of the secretion of L-cell derivatives like GLP-1, PYY Korner et al. Surg Obes Relat Dis 2007;3:597– 601

26. Control of glucose homeostasis : GLP1 & GIP actions Drucker et al. J. Clin. Invest. 117:24–32 (2007)

27. Ileal interposition Patriti et al. Surgery 2007;142:74-85

28. Rubino et al. Ann Surg 2002. Vol. 236, No. 5, 554–559

29. Proximal Small Intestine in T2DM Rubino et al. Ann Surg 2006; 244: 741-749

30. Reoperation : GJ  Duodenal exclusion Rubino et al. Ann Surg 2006; 244: 741-749

31. Rubino et al. Ann Surg 2002. Vol. 236, No. 5, 554–559 Duodenal exclusion Rapid exposure to distal bowel

32. Duodenojejunal bypass (DJB) Ileal interposition Duojejunal bypass with SG Mini-gastric bypass (MGB) or single-anastomosis gastric bypass (SAGB)

33. Endoluminal Sleeves

34. Then… what about in low BMI population?

35. BARIATRIC SURGERY Lower the BMI & Body weight METABOLIC SURGERY Reduce HbA1c & medications

36. Mortality? considerably less impact than classes II and III obesity unclear Increased risk of comorbidities T2DM, HTN, dyslipidemia, metabolic synd., OSA, PCOS, depression, NAFL Increased risk of many cancers Impaired physical & mental health-related QoL Increased psychosocial burden, esp. in women

37. Overall weight loss was excellent in patients with class I obesity after all the most established bariatric procedures. Better excess weight loss in this group of patients compared to patients with morbid obesity. Length of follow-up is short (<2 years) in most of the studies.  long-term risk / benefit ratio of surgery ????

38. Bariatric surgery: an IDF statement for obese type 2 diabetes. 2011 ASMBS Clinical Issues Committee. Bariatric surgery in class I obesity (BMI 30 – 35 kg/m 2 ). 2013

39. Indication to bariatric surgery in class I obesity Comorbidity burden >> BMI levels Obesity scoring system phenotypization beyond BMI levels for guiding therapeutic choices Position statement from IFSO, 2014

42. Schauer et al. N Engl J Med 2014;370:2002-13

43. Parikh et al. Ann Surg 2014;260:617–624 Randomized pilot trial

44. Serrot et al. Surgery 2011;150:684-91

45. 66 patients BMI 30 – 35 kg/m2 DM duration 12.5 ± 7.4 years HbA1c 9.7 ± 1.5% Cohen et al. Diabetes Care 2012

46. Estimated 10-year cardiovascular risk after RYGB in mild obesity Cohen et al. Diabetes Care 2012

47. Lee W-J et al. Arch Surg. 2011;146(2):143-148 Randomized controlled trial 30 SAGB + 30 SG HbA1c>7.5 % BMI 25 - 35 Kg/m 2, C-peptide ≥1.0 ng/mL Duration of T2DM > 6 months Baseline characteristics Duration of DM : 6.4 years (4.2–8.5 ) BMI 30.6 kg/m2 (25.1–34.7) HbA1c 10.0% (7.5–15.0)

48. Effect of duodenal exclusion at 12 months SAGB vs SG Lee W-J et al. Arch Surg. 2011;146(2):143-148

49. Lee W-J et al. OBES SURG (2014) 24:1552–1562

51. At Soonchunhyang University Seoul Hospital

52. RYGB RYGB : Low BMI vs. high BMI Low BMI (n=137)High BMI (n=266)p-value Age (years) 40.1 ± 10.636.2 ± 11.10.001 Sex Male 17 (12.4)55 (20.7)0.040 chi Female 120 (87.6)211 (79.3) Body weight (kg) 84.9 ± 9.8111.2 ± 17.2<0.001 BMI (kg/m2) 32.0 ± 1.940.8 ± 4.4<0.001 Excess weight (kg) 29.5 ± 8.455.1 ± 15.7<0.001 Comorbidities Diabetes 45 (32.8)89 (33.5)0.902 Hypertension 45 (32.8)91 (34.2)0.784 Dyslipidemia 94 (68.6)171 (64.3)0.386 Sleep apnea Confirmed 5 (3.6)35 (13.2)0.004 Suspicious 4 (2.9)15 (5.6) Arthropathy 17 (12.4)32 (12.0)0.912 PCOS 8 (5.8)31 (11.7)0.061 No. of comorbidities 1.6 ± 1.31.8 ± 1.30.183 403 patients January 2011 ~ February 2014

53. Low BMI (n=137)High BMI (n=266)p-value Follow-up duration (months) 13.5 ± 8.714.5 ± 8.10.278 At last follow-up Body weight (kg) 65.4 ± 9.580.3 ± 15.1< 0.001 BMI (kg/m 2 ) 24.7 ± 2.929.6 ± 4.5< 0.001 %EWL (%) 83.2 ± 33.164.3 ± 20.8< 0.001 EWL < 50% at 1 year (n, %) 9 (8.7)30 (15.4)0.106

55. Low BMIHigh BMIp-value DM duration (years) 5.9 ± 6.04.0 ± 5.6 0.086 Preop HbA1c 8.3 ± 1.57.8 ± 1.4 0.053 Preop C-peptide5.0 ± 2.56.2 ± 2.90.019

56. Univariate analysisMultivariate analysis OR95% CIp-valueAdjusted OR95% CIp-value Age < 50 years2.9681.159 – 7.6020.0235.7290.866 – 37.8820.070 Preoperative BMI ≥ 40 kg/m 2 5.4401.881 – 15.7360.0025.0630.990 – 25.8860.051 Duration of diabetes < 5 years4.8322.047 – 11.405<0.0015.0961.008 – 25.7620.049 Preoperative Insulin requirement5.1431.998 – 13.2410.0011.3110.205 – 8.3830.775 Preoperative laboratory results FBS < 200 mg/dL2.3800.960 – 5.8980.061 HbA1c < 8.5 %3.8461.593 – 9.2850.00320.0312.759 – 145.4210.003 C-peptide ≥ 3 ng/mL5.6061.627 – 19.3110.00638.8043.562 – 422.7820.003 At last follow-up EWL ≥ 50 % *2.4501.325 – 8.9830.01117.7482.470 – 127.5310.004

57. Purpose Metabolic resolution >> weight loss RYGB or SAGB RYGB or SAGB (malabsroptive procedures) Effective comorbidity resolution and weight loss Malabsoptive vs. Restrictive procedures Better diabetic resolution after BYPASS Different response of diabetic resolution? Difference in preoperative diabetic characteristics Patient selection : DM duration, preoperative C-peptide… Long-term follow-up is necessary......

58. THANK FOR YOUR KIND ATTENTION.