1 Surgical Treatment of Type 2 Diabetes: Do Surgeons have a Better Treatment? John Bantle, MD Division of Endocrinology and Diabetes Department of Medicine University of Minnesota
2 Disclosure Information I have no financial relationship to disclose. I will not discuss off label or investigational product use in my presentation.
3 Goals of Presentation To review expected weight loss with medical and surgical treatments. To describe the bariatric procedures in current use. To summarize the effects of bariatric surgery on type 2 diabetes. To review potential adverse outcomes of bariatric surgery.
4 Natural History of Type 2 Diabetes Glucose (mg/dl) Postmeal Glucose Fasting Glucose 50 Relative Function (%) Prediabetes (IFG, IGT) Clinical Diagnosis Insulin Resistance -Cell Function Onset of Diabetes Years Adapted from: Simonson GD, Kendall DM. Coron Artery Dis. 2005;16(8):
5 To Avoid Type 2 Diabetes If you are lean, try to stay lean. If you are overweight, try to lose weight.
6 To lengthen thy life, lessen thy meals Benjamin Franklin 1733 and quicken thy heart with exercise
9 Action for HEAlth in Diabetes (Look AHEAD) NIH sponsored clinical trial of lifestyle modification to reduce CV events in type 2 diabetic subjects. Random assignment to an intensive lifestyle intervention or a program of diabetes support and education (control group). 5,145 subjects randomized Multicenter All participants continued to receive diabetes care from their own physician
10 Intensive Lifestyle Intervention (ILI) Group Structured hypocaloric, low fat diet Regular use of meal replacements Regular exercise (goal 175 minutes per week) Behavioral components Weekly group or individual sessions months 1-6, frequent subsequent contact Toolbox including orlistat as rescue strategy Refresher courses and campaigns Goal to achieve 7% average weight loss in the first 6 months and maintain it thereafter
11 Four Year Results (Averaged Across All 4 Years) Arch Intern Med 2010;170:1566 ILI Control P value Weight loss (% initial) -6.2* -0.9* < Fitness gain (METS) < Hb A1c (%) < Systolic BP (mmhg) -5-3 < LDL chol (mg/dl) HDL chol (mg/dl) < Triglycerides (mg/dl) < * At 4 years, weight change was -4.7% and -1.1%, respectively
12 Why is Wight Loss so Difficult for Most People to Accomplish? Probably because each of us has a body weight that our hypothalamus works to maintain. This weight may be defended as is, for instance, body temperature. 1) Deficient caloric intake compensated for by decrease in metabolic rate and decrease in physical activity. 2) Excess caloric intake suppresses appetite, some calories dissipated as heat.
13 Biochemistry of Energy Regulation Leptin: produced in adipose tissue, circulates in proportion to body adiposity. Insulin: circulates in proportion to body adiposity. Neuropeptide Y: potent stimulator of food intake, increases during fasting, inhibited by leptin. Agouti-Related Protein: stimulates appetite. Ghrelin: signals hunger, increases food intake. Peptide YY: signals satiety, decreases food intake, inhibits gut motility. Glucagon-Like Peptide 1: increases satiety.
15 Bariatric Surgery
16 Jejunoileal Bypass for Morbid Obesity: Late Follow-up in 100 Cases Hocking MP, et al. N Engl J Med 1983;308: Results from 100 patients who underwent jejunoileal bypass and had 5 or more years of follow-up. Procedure: end-to-side anastomosis of the jejunum 30 cm from the ligament of Treitz to the ileum 10 cm from the ileocecal valve. Mean weight loss at 5 years was 46.6 kg. Complications (n): progressive hepatic abnormalities (29), cirrhosis (7), nephrolithiasis (21), cholelithiasis (14), chronic diarrhea (58), chronic hypokalemia (33). The investigators abandoned the procedure.
17 Bariatric Surgical Procedures in Current Use 1) Vertical banded gastroplasty 2) Laparoscopic gastric banding 3) Roux-en-Y gastric bypass 4) Biliopancreatic diversion with duodenal switch 5) Sleeve gastrectomy
20 Meta-analysis: Surgical Treatment of Obesity Maggard MA, et al. Ann Intern Med 2005;142: Meta-analysis of 147 studies of bariatric surgery for obesity. Weight loss 12 months > 36 months Gastric banding 30.2 kg 34.8 kg Gastric bypass 43.5 kg 41.5 kg Duodenal switch 51.9 kg 53.1 kg
21 Maggard MA, et al (continued) Mortality < 30 Days > 30 days Gastric banding 0.02 % 0.1 % Gastric bypass 0.3 % 0.6 % Duodenal switch 0.9 % 0.3 % Adverse Events All GI* Other + Gastric banding 7.0 % 13.2 % Gastric bypass 16.9 % 18.7 % Duodenal switch 37.7 %? # * Including reflux, vomiting, dysphagia, dumping syndrome and others. + Including anastomotic leak, stenosis, bleeding, need for reoperation and others. # Not reported in all categories.
22 Lifestyle, Diabetes and Cardiovascular Risk Factors 10 Years after Bariatric Surgery Sjostrom L, et al. N Engl J Med 2004;351: Swedish obese subjects who chose to undergo bariatric surgery compared to 647 control subjects who received nonsurgical treatment for obesity as was customary at their medical center. Subjects in the two groups were matched on 18 variables including gender, age, weight, height, systolic BP and diabetes status. After 10 years, weight changes were: control group %, gastric banding group %, vertical banded gastroplasty group % and gastric bypass group % (control vs. surgery, p<0.001).
24 Sjostrom L, et al (continued) Control Group Surgery Group P Value Recovery from preexisting diabetes 13% 36% Incidence of new diabetes 24% 7% <0.001
25 Effects of Bariatric Surgery on Mortality in Swedish Subjects Sjostrom L, et al. N Engl J Med 2007;357: Overall mortality of 4047 Swedish obese subjects during an average follow-up of 10.9 years reported. 129 (6.3%) subjects in the control group and 101 (5.0%) subjects in the surgical group died. Hazard ratio for surgical group was 0.76 when compared to the control group (95% CI 0.59 to 0.99, p=0.04). Most common causes of death were MI (control 25, surgery 13) and cancer (control 47, surgery 29).
26 Long-Term Mortality after Gastric Bypass Surgery Adams TD, et al. Engl J Med 2007;357: Retrospective cohort study comparing 7,925 patients who underwent gastric bypass surgery for obesity to 7,925 obese subjects who applied for driver s licenses; matching based on gender, age and BMI. During mean follow-up of 7.1 years, adjusted mortality in the surgery group decreased by 40% as compared to the control group (37.6 vs deaths per 10,000 person years, p<0.001). Cause specific mortality in the surgery group decreased by 92% for diabetes.
27 Pories, W.J., et al., Who would have thought it? An operation proves to be the most effective therapy for adult onset diabetes mellitus. Ann Surg, (3): p ; discussion
28 Porries WJ, et al (continued) Long-term follow-up of 608 patients who underwent open gastric bypass n Mean Weight (kg) Mean BMI (kg/m 2 ) Pre-op year years years
29 Porries WJ, et al (continued) 121 of 146 (83 %) patients with diabetes developed and maintained normal blood glucose and A1c without medications. Complications: Perioperative mortality 1.5 % Reoperation 2.8 % Wound infections 8.7 % Anastomotic stenosis 3.0 % Splenic tears 2.5 % Subphrenic abscess 2.5 % Incisional hernia 24 % B 12 deficiency 40 % Anemia 39 % Cholelithiasis 11 % Hypoglycemia 5.7 %
30 Weight and Type 2 Diabetes After Bariatric Surgery: Systematic Review and Meta-analysis Buchwald H, et al. Am J Med 2009;122: Meta-analysis of 621 studies published between 1/1/1990 and 4/30/2006; 73% single arm and 58% retrospective. 135,246 patients; 22.3% (30,160 patients) had diabetes. Mean weight loss < 2 years 36.6 kg; > 2 years 41.6 kg. Diabetes resolution (no diabetes meds, A1c < 6.0% and/or fasting glucose <100 mg/dl): Laparoscopic gastric banding 56.7% Gastric bypass 80.3% Duodenal switch 95.1%
31 Buchwald H, et al (continued) Overall 30 day or less mortality was 0.28% The available information on nonfatal adverse effects of the bariatric surgery procedures is so heterogeneous, sparse and poorly reported that it does not allow meaningful review.
32 Mechanisms of Improvement 1. Reduced need for glucose disposal 2. Weight loss induced increase in insulin sensitivity 3. Weight loss induced decreases in lipotoxicity and inflammation 4. Changes in gut hormones (increases in GLP-1 and peptide YY, decrease in ghrelin)
33 Randomized Clinical Trials
34 Adjustable Gastric Banding and Conventional Therapy for Type 2 Diabetes: A Randomized Controlled Trial Dixon JB, et al. JAMA 2008;299: obese (BMI kg/m 2 ) patients with diabetes of less than 2 years duration randomly assigned to conventional therapy or laproscopic adjustable gastric banding. Conventional therapy included lifestyle modification with structured low fat diet, 200 minutes physical activity per week, contact every 6 weeks, and diabetes and weight loss medications (no GLP-1 mimetics). Baseline A1c values: Conventional 7.6%, Surgery 7.8%. Follow-up lasted 2 years. Dropouts: 4 Conventional therapy patients and 1 Surgery patient.
35 Dixon: Outcomes at 2 Years Conventional Surgery P value Weight loss < (kg) Hb A1c (%) < Glucose (mg/dl) Insulin (uu/ml) < 0.001
36 Dixon, et al (cont.) 73 % (22/30) of Surgery and 13% (4/30) of Conventional patients achieved remission of diabetes. Amount of weight loss, not the method, was related to remission of diabetes. Diabetes medication use was less in Surgery than Conventional patients (4 vs 28 patients). There were no serious complications in either group.
37 Bariatric Surgery versus Intensive Medical Management in Obese Patients with Diabetes Schauer PJ, et al. New Engl J Med 2012;366: obese (BMI kg/m 2 ) patients with type 2 diabetes and Hgb A1c > 7.0% randomly assigned to intensive medical therapy or gastric bypass or sleeve gastrectomy. Conventional therapy included lifestyle counseling for weight loss and all approved diabetes medications. Primary endpoint: percentage of patients with Hgb A1c < 6.0% (with or without medications). Follow-up lasted 1 year. Dropouts: 9 conventional therapy and 1 sleeve gastrectomy patients.
38 Schauer: Outcomes at 1 Year Medical Therapy Gastric Bypass Sleeve Gastrectomy Weight Loss % %* %* A1c < 6.0% 5 of 41 (12%) 21 of 50* (42%) 18 of 49* (37%) * p < 0.01 vs Medical Therapy
41 Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes Mingrone G, et al. N Engl J Med:366: obese (BMI > kg/m 2 ) patients with type 2 diabetes for at least 5 years and Hgb A1c > 7.0% randomly assigned to conventional medical therapy or gastric bypass or biloipancreatic diversion. Conventional therapy included lifestyle modification and diabetes medications as necessary. Primary endpoint: diabetes remission. Follow-up: 2 years. Dropouts: 2 conventional therapy, 1 gastric bypass and 1 biliopancreatic diversion patients.
42 Mingrone: Outcomes at 2 Years Medical Therapy Gastric Bypass Biliopancreat Diversion Weight Loss % %* %* Remission of Diabetes 0 of of 20* (75%) 19 of 20* (95%) * p < vs Medical Therapy
44 Diabetes Surgery Study (DSS) Multicenter clinical trial comparing gastric bypass surgery to intensive medical management in people with type 2 diabetes. Participating centers: University of Minnesota, Columbia University, Mayo Clinic and University of Taiwan. 120 type 2 diabetic volunteers have been randomly assignment to treatment arm.
45 DSS (continued) Primary endpoint: composite of A1c < 7.0%, LDL cholesterol < 100 mg/dl and systolic BP < 130 mmhg.
46 Postoperative Management After Bariatric Surgery Intake of g protein daily After gastric bypass and duodenal switch, supplementation with: Multivitamin with folate and thiamine Iron Vitamin B12 Calcium Vitamin D
47 Suggested Schedule for Postoperative Monitoring (1) Preop 1 m 3 m 6 m 12 m 18 m 24 m Annual CBC, LFTs, glucose, x x x x x x x x creatinine, electrolytes Ferritin x x x x x x Albumin x x x x x x Folate x x x x x x Vitamin B1 x x x x x x x Vitamin B12 x x x x x x Calcium, PTH, 25-OH D x x x x x x DEXA x x x x (1) Heber D, et al. Endocrine and Nutritional Management of the Post-Bariatric Surgery Patient: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2010;95:4823.
48 DAVID 50 year old man who had undergone roux-en- Y gastric bypass for obesity. Preoperative weight was kg and BMI 41.2 kg/m 2. Following surgery, he lost 46 kg. Two years after surgery, he started having episodes of transient loss of consciousness for which no explanation could be found.
49 David Test Results High Carb Meal Low Carb Meal Glucose (mg/dl) Insulin (uu/l) Glucose (mg/dl) Insulin (uu/l) Fasting min min min min min
50 Post-Gastric Bypass Hyperinsulinemic Hypoglycemia First described by GJ Service and colleagues (N Engl J Med 2005;353:249-54). Six patients with postprandial neuroglycopenia after gastric bypass. Mechanistic possibilities: 1) Rapid absorption of ingested nutrients coupled with failure to adaptively decrease insulin secretion after gastric bypass-induced weight loss. 2) Increase in beta cell mass post-gastric bypass induced by increased GLP-1 or other beta cell trophic peptides.
51 Hyperinsulinemic Hypoglycemic Developing Late After Gastric Bypass Bantle JP, et al. Obesity Surgery 2007: Diagnostic criteria: 1) Postprandial hypolycemia with neuroglycopenia developing > 1 year after gastric bypass, 2) Spontaneous correction of hypoglycemia, 3) Normal fasting glucose and serum insulin, 4) Hyperinsulinemia at the time of hypoglycemia or, after a mixed meal, plasma glucose < 50 mg/dl and serum insulin > 50 uu/l.
52 Treatment of Post Gastric Bypass Hyperinsulinemic Hypoglycemia Low carbohydrate diet Acarbose with meals containing carbohydrate Glucose tablets (1 or 2) at first symptoms of hypoglycemia Feeding through gastrostomy tube placed in remnant stomach Partial pancreatectomy Reversal of gastric bypass
53 Conclusions on Bariatric Surgery for Diabetes
54 Potential Benefits of Bariatric Surgery Weight loss: Duodenal Switch > Gastric Bypass > Laparoscopic Gastric Banding Reduced need for medications Improved diabetes control Remission of diabetes Improvements in blood pressure, blood lipids, sleep apnea, osteoarthritis, quality of life Reduced long-term mortality
55 Potential Risks of Bariatric Surgery Perioperative (early) mortality rate of % Anastomotic leaks Wound infections Thromboembolic events Pneumonia Late complications including nausea, vomiting, anastamotic ulcers, internal hernias, gallstones, oxalate nephropathy, dumping syndrome, nutritional deficiencies (iron, calcium, vitamins B 1, B 12, D) and, perhaps, hypoglycemia
56 NIH Consensus Development Panel Statement on Bariatric Surgery for Diabetes* Should be considered only in people: 1) who are motivated and well informed, 2) in whom the operative risks are acceptable, and 3) with BMI > 35 kg/m 2. Surgery should be performed by a surgeon with substantial experience in obesity surgery * National Institutes of Health Consensus Development Panel. Gastointestinal surgery for severe obesity. Ann Intern Med 1991;115:956.
57 My Conclusions Bariatric surgery should be considered in type 2 diabetic patients with BMI > 35 kg/m 2 ; patients with BMI kg/m 2 may also benefit but this has not been established. Laparoscopic gastric bypass is the preferred procedure. The earlier surgery is done the better; remission of diabetes is predicted by short duration of diabetes, need for few diabetes medications and high postprandial C- peptide.
58 Thanks For Your Attention