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

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)

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

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

Dixon et al. Lancet 2012; 379:

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

The SOS intervention study

Adjusted hazard ratio 0.17 ( ) Carlsson et al. N Engl J Med 2012;367:

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

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

Mingrone et al. N Engl J Med 2012;366: 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%

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

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, ) 9.5 (95% CI, ) <0.001 Time to normalization (months) 10±24 ± Mingrone et al. N Engl J Med 2012;366:

Schauer et al. N Engl J Med 2012;366: 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

At 12 months Schauer et al. N Engl J Med 2012;366:

Changes in Diabetes Control Over 3 Years Schauer et al. N Engl J Med 2014;370: 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)

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

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

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

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

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

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

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

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: Diet induced weight loss

Mason et al. Obesity Surgery, 15, 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

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

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

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

Proximal Small Intestine in T2DM Rubino et al. Ann Surg 2006; 244:

Reoperation : GJ  Duodenal exclusion Rubino et al. Ann Surg 2006; 244:

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

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

Endoluminal Sleeves

Then… what about in low BMI population?

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

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

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 ????

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

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

Schauer et al. N Engl J Med 2014;370:

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

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

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

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

Lee W-J et al. Arch Surg. 2011;146(2): Randomized controlled trial 30 SAGB + 30 SG HbA1c>7.5 % BMI 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)

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

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

At Soonchunhyang University Seoul Hospital

RYGB RYGB : Low BMI vs. high BMI Low BMI (n=137)High BMI (n=266)p-value Age (years) 40.1 ± ± Sex Male 17 (12.4)55 (20.7)0.040 chi Female 120 (87.6)211 (79.3) Body weight (kg) 84.9 ± ± 17.2<0.001 BMI (kg/m2) 32.0 ± ± 4.4<0.001 Excess weight (kg) 29.5 ± ± 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 ± ± patients January 2011 ~ February 2014

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

Low BMIHigh BMIp-value DM duration (years) 5.9 ± ± Preop HbA1c 8.3 ± ± Preop C-peptide5.0 ± ±

Univariate analysisMultivariate analysis OR95% CIp-valueAdjusted OR95% CIp-value Age < 50 years – – Preoperative BMI ≥ 40 kg/m – – Duration of diabetes < 5 years – < – Preoperative Insulin requirement – – Preoperative laboratory results FBS < 200 mg/dL – HbA1c < 8.5 % – – C-peptide ≥ 3 ng/mL – – At last follow-up EWL ≥ 50 % * – –

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......

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