Metabolic Effects of Bariatric Surgery in Patients With Moderate Obesity and Type 2 Diabetes
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Metabolic Effects of Bariatric Surgery in Patients With Moderate Obesity and Type 2 Diabetes

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Analysis of a randomized control trial comparing bariatric surgery with

Analysis of a randomized control trial comparing bariatric surgery with
intensive medical treatment.

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  • The mechanism of improved glycemic control appears to involve improvement in insulin sensitivity, with a marked reduction in insulin levels and improvement in the HOMA-IR index, which may be linked to the attenuation of chronic inflammation, as suggested by the greater reduction in high-sensitivity CRP in the surgery groups than in the medical-therapy group.

Metabolic Effects of Bariatric Surgery in Patients With Moderate Obesity and Type 2 Diabetes Metabolic Effects of Bariatric Surgery in Patients With Moderate Obesity and Type 2 Diabetes Presentation Transcript

  • Background
  • Background
  • BMI Classification < 18.5 UnderweightBariatric surgery 18.5–24.9 25.0–29.9 normal weight overweightLimitations to medical 30.0–34.9 class I obesity treatment 35.0–39.9 class II obesity class III ≥ 40.0 obesityBMI >40, or >35 kg/m2 if co-morbidityRoux-en-Y gastric bypass, sleeve gastrectomy
  • RCT, N = 60 T2DM with severe obesity:DM REMISSION: BMI ~ 45, duration DM ≥ 5 years, HbA1c ~ 8.5 % Medical therapy < gastric-bypass < biliopancreatic SxConventional medical therapy (none) (75%) or gastric (95%) or bypass HbA1C decrease: diversion biliopancreatic 1% 2% 3.5 %BMI and weight loss did NOT predictremission* at 2 years Primary end point: diabetes improvement in hyperglycemia. *FPG <100 mg/dl, HbA1c <6.5% without medication for 1 year
  • Prospective RCT, N = 150 subjectsT2DM with modest obesity BMI 27–42 kg/m2Primary end point: Resolution of T2DM at 1 year (HbA1c < 6%).
  • ReT2DM duration 8 yrs, BMI ~36, HbA1C ~9.2% Medical Rx RYGB Sleeve GDM resolution 12% 42% 37%HbA1C decrease: 1.5% 2.8% 2.6%Weight loss: 5.4 kg 29 kg 25 kgInsulin resistance (HOMA-IR) improved after Sx.
  • BackgroundNo data from RCT: long-term metabolic effects and clinical efficacy outcomes after bariatric surgery in moderately obese subjects with poorly controlled T2DM.
  • BackgroundThis study is a 2-year extension of a metabolic substudy of the STAMPEDE trial.Evaluate the effects of the three treatments on Glucose regulation Pancreatic B-cell function (insulin secretion/sensitivity) Body composition
  • INCLUSION CRITERIAAge 20 – 60 yrT2DM, HbA1c of ≥7.0%BMI 27 - 43 kg/m2Candidate for generalanesthesiaFirst consecutive 60 subjectsrandomized in main trial~20 randomized to each groupF/U at DM clinic q 3 moBaseline, at 12 and 24 mo- Metabolic assessment(Mixed-meal tolerance test)- Body compositionmeasurement (DEXA)
  • Liquid mixed meal - commercial product Mixed-meal test (Boost; 8 ounces, 350 kcal, 55% carbohydrate, 25% protein, 20% fat) Glucose tolerance, insulin sensitivity & secretion Diabetes meds stopped 24 h before study, including insulin. NPO overnight 12-14 h.Time Plasma C-peptide Insulin GLP-1, Glucagon Lipids, glucose GIP HbA1c, adipokines, complete metabolic panel0 min x x x x x x30 min60 min x90 min120 min x
  • CalculationsInsulin secretion rate (ISR)Pancreatic B-cell function: measure by insulin secretion / insulin resistance (disposition) index (Matsuda index)
  • Statistical analysis No power calculations for the substudy measures due to lack of published data regarding specified metabolic outcome measures at the time of trial design (2004–2005), and because of exploratory nature of substudy. Continuous variables with a normal distribution: means and SDs. Variables with a non-normal distribution: medians and interquartile ranges. Categorical variables: frequencies; tested with x2 statistic or Fisher exact test (two-tailed). One-way ANOVA: continuous laboratory parameters Comparisons between treatment groups: Student t test or Wilcoxon test. Glucose and insulin measures collected during the mixed meal tolerance test were plotted graphically.
  • Patients 10% lost to F/U N =20 -> 17 N =20 -> 18 N =20 -> 19
  • Baseline characteristics
  • *P for IMT vs. gastric bypass †P for IMT vs. sleeve gastrectomy ‡P for gastric bypass vs. sleeve gastrectomyGlycemic control Gastric bypass: Significantly greater reduction in FPG, HbA1c
  • *P for IMT vs. gastric bypass †P for IMT vs. sleeve gastrectomy ‡P for gastric bypass vs. sleeve gastrectomyCardiovascular risk Both surgery groups - HDL cholesterol - TG, hsCRP
  • *P for IMT vs. gastric bypass †P for IMT vs. sleeve gastrectomy ‡P for gastric bypass vs. sleeve gastrectomyBW, body composition, adipokines Bariatric Sx groups: Greater BW loss after bariatric Sx at 12 months and maintained at 24- mo. Body weight, BMI, and absolute change in total body fat percent at 24 mo.
  • *P for IMT vs. gastric bypass †P for IMT vs. sleeve gastrectomy ‡P for gastric bypass vs. sleeve gastrectomyBW, body composition, adipokinesReduction in percent truncal fat was greater in gastric bypass versus sleevegastrectomyLeptin levels reduced markedly after surgical weight loss, especially gastricbypass.
  • Mixed meal tolerance
  • FPG, 2hPPGB -> Sleeve -> Fasting C-peptide (not IMT) IMT 2x PP C-peptide (GB > Sleeve)
  • Insulin sensitivityMedian values for the insulin sensitivity (Matsuda index) in noninsulin-using subjects increased at 24 months after gastric bypass by 2.7-fold 1.2-fold after sleeve gastrectomy Did not change with IMTThe absolute change in median insulin sensitivity (Matsuda index) at 24 months tended to be higher in gastric bypass compared with sleeve gastrectomy despite equivalent weight loss.
  • Pancreatic hormone functionThe absolute change in median values for pancreatic B-cell function (oral disposition index) at 24 months Markedly greater in gastric bypass than IMT (P <0.001) but not different between sleeve gastrectomy and medical therapyB-cell function from baseline 5.8-fold increase in gastric bypass Negligible increases in sleeve gastrectomy and IMT.
  • Incretin response P value 1 for IMT vs. gastric bypass P value 2 IMT vs. sleeve gastrectomy P value 3 Gastric bypass vs. sleeve gastrectomy
  • DiscussionBariatric surgery provides durable glycemic control compared with intensive medical therapy at 2 years.Despite similar weight loss as sleeve gastrectomy,Gastric bypass uniquely restores pancreatic B-cell function and reduces truncal fat, thus reversing the core defects in diabetes.
  • Our results extend the findings from our initial 12- month report andSuggest factors beyond weight loss that are specific to intestinal bypass patients help regulate glucose levels and restore pancreatic B-cell function.
  • In gastric bypass patients, both insulin sensitivity and secretion components increased but,Despite comparable weight loss in sleeve gastrectomy, insulin sensitivity was only partially restored and pancreatic B-cell function did not improve.
  • Both bariatric surgery procedures stimulated incretins with markedly increased postprandial GLP-1 levels as noted in previous observational studies in obese patients with type 2 diabetes.However, divergence in postprandial GIP levels were noted, with a reduction seen only in gastric bypass that may be related to anatomical exclusion of the duodenum (which produces GIP) or may be reflective of improved GIP action that is noted to be defective in type 2 diabetes.
  • Marked improvements in insulin sensitivity and glycemic control observed in the gastric bypass group suggest factors specifically linked to the presence of abdominal (truncal) fat.Ectopic abdominal fat presence has long been recognized to induce insulin resistance, subclinical inflammation, and cardiovascular risk specific to type 2 diabetes.
  • In the current study, adipogenic inflammation was significantly reduced after both bariatric procedures, especially gastric bypass, mediated by factors such as free fatty acids, leptin, and C-reactive protein, which impair glucose uptake by insulin-dependent tissues (muscle and liver).
  • LimitationA limitation of this study is the validity of the incretin hormone responses that were obtained after the assigned interventions.Concentrations of GLP-1 and GIP were obtained at fasting and at 60 min after meal ingestion, and this likely underestimates the incretin surge that normally occurs rapidly (within 15 min) after meal ingestion.
  • ApplicationFurther studies are warranted to thoroughly investigate the long-term effects of bariatric surgery on incretin responses and action to modulate insulin secretion.More vigorous and behavioral/lifestyle modification strategies as used in the Look AHEAD trial that aggressively target weight loss are clearly needed.Future randomized control trials are needed to compare such strategies results with bariatric surgery.