MISS Journal Club 2012 RYGB/BPD-DS Goal: to review 4 important and clinically relevant papers from 2011 on Gastric Bypass & BPD-DS

Article #1 Diabetes Care Jan; 35 (1): 42-46

Objective GLP-1 levels and incretin effect on insulin secretion accounts for improved glycemic control after Gastric Bypass (GB) Long-term effect of GB is variable - diabetes re-emerges in up to 30% Aim: To characterize the magnitude & variance of the change of glucose & GLP-1 concentrations, and to identify determinants of glucose control, up to 2 years after GB

Methods N=15 – 14 female – T2DM for 2.5 ± 2.5 years – HbA1c 7.1 ± 1.1% – BMI 43.7 ± 4.9 – age 47.5 ± 9.1 years Evaluated preop and 1, 12, and 24 months after GB Underwent a 50 g 3-hr OGTT followed by an isoglylcemic iv glucose challenge (isoG IVGT) Assessed mean changes and variances of each parameter

Results

Results cont.

Univariate analysis – Changes in glucose AUC over time were positively associated with weight loss and negatively associated with HOMA-B and ISI composite Multivariate analysis – weight loss, HOMA-B, and ISI were determinants of glucose AUC GLP-1 AUC was positively related to Insulin AUC

Discussion

Article #2 Archives of Surgery 2012; Jan 16.

Background 17 RYGB vs. LAGB comparative studies to date – 2 RCTs (Nguyen NT et al, Angrisani L et al) – 3 case-matched studies – 12 others Many methodological flaws in these studies – Small numbers, different patient populations Current study aim: compared RYGB to LAGB in matched pairs, treated during same time period, by same surgeons

Methods Inclusion criteria – BMI <50 – Primary bariatric surgery only, no revisional cases – Min of 6 years follow-up (OR date <2005) RYGB and LAGB cases matched according to – BMI – Sex – Age

Methods LAGB: LAP- BAND (BioEnterics) or Swedish Adjustable Gastric Band (SAGB) RYGB: retrocolic/retrogastric, 10-15mL pouch, ‘short’ BP limb, 100cm Roux limb Follow-up schedule: LAGB – monthly x 6 months, q2 months for 6 months, q3 months in Yr 2, q6 months thereafter – band adjustments prn, Barium studies q18-24 months RYGB – 1 month, q3 months for Yr 1, q6 months thereafter Labs annually, QoL assessment, food tolerance questionnaire

Outcome measures Weight loss: – ‘Excellent’residual BMI <30 – ‘Acceptable’residual BMI <35 – ‘Failure’EWL 35 Early ( 30 days) complications Reoperations

Results N=442 – 221 LAGB patients vs. 221 RYGB patients Comparable sex ratio, age, BMI Follow-up 6 years: – 92.8% post-LAGB and 91.9% post-RYGB

Results Weight loss Maximal weight loss: – 36 months…64.8% EWL – 18 months…78.5% EWL p<0.001

Results Failures (EWL 35, or need for reversal/conversion) – 3 years post-op LAGB 31.7% RYGB 6.9% – 6 years post-op LAGB 48.3% RYGB 12.3% p<0.001

Results No mortality in either group Early complications: RYGB 17.2% LAGB: 5.4% p<0.001 Major morbidity (technical complications): RYGB3.6% LAGB: 2.2% p=0.54 Long-term complications/reoperations RYGB 19.0% / 12.7% LAGB: 41.6% / 26.7% p<0.001

Results

Overall, band removal necessary in 21.3% (n=47) …of whom 13.1% (n=29) underwent a further bariatric procedure

Results Quality of life Improved in both groups Quicker & greater improvement after RYGB Food tolerance Better after RYGB Worsened over time after LAGB

Results Comorbidity improvement Lipid profile:

Discussion

Article #3 Ann Intern Med 2011; 155(5):

Background Gastric bypass (RYGB) vs. Duodenal Switch (DS) Uncontrolled studies suggest that DS induces greater weight loss than RYGB – Prachand et al, Ann Surg 2006 – Marceau et al, Obes Surg 2007 No RCT comparing these procedures Aim To conduct a randomized trial comparing RYGB vs. DS in super-obese (BMI>50) …w.r.t. weight loss, CVD risk factors and QoL

Methods Unblinded prospective randomized trial 2 academic medical centers (Norway & Sweden) N= 60 (RYGB=31, DS=29)* Follow-up 2 years Inclusion criteria: – BMI – Age years – Failed non-surgical weight loss attempts Exclusion criteria: – Previous bariatric or major abdo surgery – Severe cardiopulmonary disease, cancer, steroids - Computer-derived - Patient & surgeon masked to treatment allocation until 1wk prior to surgery * Power calculation performed, based on retrospective data: needed minimum of 26 pts in each group to give 80% power to detect a significant difference in outcomes

Methods Techniques Standardized Laparoscopic techniques RYGB – 25ml pouch, 50 cm BP limb, 150 cm Roux limb, linear stapler DS – One-stage, Sleeve (30-32 F bougie), 100 cm common channel, 200 cm alimentary limb, hand-sewn DI anastomosis Mesenteric defects not closed in either procedure Routine postop diet Follow-up: same for both procedures (phased diet, vitamins, ursodiol) – Clinical 6 weeks, 6 months, 1 year, 2years

Methods Primary end-point – Change in 2 years Secondary end-points – CV risk factors – Health-related QoL (SF -36) – Body composition (bioelectrical impedance analysis) – Vitamin concentrations – Adverse events

Results

Baseline characteristics … Similar for both groups Data in mean ± 2SD, unless stated as % RYGB (n=31)DS (n=29) Age, yrs35.2 ± ± 5.3 BMI, kg/m ± ± 3.5 Female/male %74/2666/34 Diabetes %16%21% HTN %26%28% CRP level117 ± ± 76

Results Weight loss at 2 years DS was associated with greater weight loss p<0.001 Mean Wt loss: RYGB: 50.6kg DS: 73.5kg

Results Body composition Significant reductions in both groups [RYGB vs. DS] – Waist circumference: ↓ 36.7 cm vs. ↓ 51.5 cm, p<0.001 – Hip circumference: ↓ 31.7 cm vs. ↓ 45.6 cm, p<0.001 – Sagittal diameter: ↓ 11.8 cm vs. ↓ 14.6 cm, p<0.001 All measure were significantly greater in DS group DS patients lost significantly more fat mass and fat- free mass

Results Markers of CV risk – Blood pressure – Cholesterol – Fasting glucose – Insulin levels – CRP level Generally improved in both 2 yrs DS led to greater improvement in TC, LDL and HDL levels

Results Adverse events DS group had significantly more adverse events overall, compared to RYGB group – Overall complications … 62% vs. 32%, p=0.021 – Late (>30-day) complications… 41% vs. 29%, p=0.320

Results

Vitamin concentrations DS had lower Vitamin A and Vitamin D 2 yrs Health-related QoL RYGB: 7 of 8 subscores of SF-36 improved at 2 yrs DS: 5 of 8 subscores of SF-36 improved at 2 yrs

Discussion

Article #4 Diabetes Care 2011; 34(3):

Background Intensive glycemic control, achieved medically, does not reduce CV events in patients with well established DM – Actually assoc with higher mortality (ACCORD trial, PROactive trial) – <50% Diabetics are well controlled (ADA) Buchwald meta-analysis 2009: – Bariatric surgery led to remission/improvement of DM in 78%/87% – BPD superior to RYGB Authors have previously published high DM remission rates after BPD. No long term follow-up available

Aim To assess the effect of BPD vs. Conventional Medical Therapy on diabetic complications

Methods Longitudinal case-control study, not randomized Single center (Rome) N=110 obese patients (BMI>35), aged years* All had newly diagnosed T2DM (FBG >7.0mmol/L x2, or positive OGTT) 10 years follow-up BPD & Conservative therapy groups matched for: – Gender – Age – BMI – Cholesterol & Triglyceride levels – Smoking status * Power calculation performed to calculate appropriate sample size …needed 30 in each group to give 90% power to detect a ΔGFR of 25%

Methods Exclusion criteria: – CV event in 6 months prior to enrollment – Advanced CCF – Severe angina – Creatinine >1.6mg/dL – Malignancy – Portal HTN ‘Run-in’ period – all subjects went on 3 month low cal diet prior to study group allocation ‘Conservative’ treatment – Sulphonylurea or insulin and/or metformin, supervised by a Diabetologist BPD – Open,

Methods End-points Primary – % variation in GFR Secondary – Incidence of nephropathy, HTN, hyperlipidemia, CV events – % recovering from T2DM over 10 years follow-up – Change in weight, HbA1C, glucose, lipid profile, BP, Framingham risk score – Change in insulin sensitivity measured only in BPD group

Results 110 enrolled, only 50 met inclusion criteria/entered treatment groups after 3 month diet Baseline characteristics similar in both groups

Results Early complications: N=2 (9.1%) in BPD group Respiratory infectionn=1 Wound infectionn=1 Late complications: N=5 (22.7%) in BPD group Incisional hernia n=3 Marginal ulcer n=2

Results Diabetic complications Nephropathy (relative % variation in GFR): – Deteriorated in controls (-45.6 ± 18.7%) – Marginally improved in BPD group (+4.2 ± 31.3%) % pts with microalbuminuria Baseline2 years10 years BPD31.8%9.1% 0% Controls14.3%28.6%All cases worsened p-value

Results Progression from no nephropathy at study entry, to nephropathy at 10 yrs: – BPD group 9% – Controls 50% p=0.002

Results CV events BPD groupn=0 Controls n=4 (3 MI’s, one stroke) CV risk

Results Hypertension Hyperlipidemia Diabetes recovery Baseline10 years BPD (n=22)55%0% Controls (n=28)64%57% Baseline1 year10 years BPD100%0% Controls100%45%? Baseline10 years BPD (n=22)64%27% Controls (n=28)71%75% Prevalence

Results Weight changes

Results HbA1C FBG

Discussion