Other Ways to Achieve Metabolic Control Nestor de la Cruz- Muñoz, MD, FACS Associate Professor of Clinical Surgery Chief, Division of Laparoendoscopic and Bariatric Surgery DeWitt Daughtry Family Department of Surgery University of Miami Miller School of Medicine Miami, Florida
STANDARDS OF MEDICAL CARE IN DIABETES 2012
Recommendations: Bariatric Surgery Consider bariatric surgery for adults with BMI >35 kg/m 2 and type 2 diabetes (B) After surgery, life-long lifestyle support and medical monitoring is necessary (B) Insufficient evidence to recommend surgery in patients with BMI <35 kg/m 2 outside of a research protocol (E) Well-designed, randomized controlled trials comparing optimal medical/lifestyle therapy needed to determine long-term benefits, costeffectiveness, risks (E) ADA. V. Diabetes Care. Diabetes Care 2012;35(suppl 1):S27.
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Bariatric Surgery A Systematic Review and Meta-analysis Impact of Bariatric Surgery on Diabetes TOTAL* GASTRIC BYPASS OUTCOME t (n/n) % [95%CI] t (n/n) % [95% CI] % Patients Diabetes Resolved 63 (1,846) 76.8 [70.7, 82.9] 26 (989) 83.7 [77.3, 90.1] HbA1C (%) Reduction (Diabetics)** 6 (171) -2.4 [-3.8, -1.0] 4 (88) -3.0 [-5.0, -1.1] Fasting Glucose (mmol/l)** 14 (296) -4.0 [-5.2, -2.7] 7 (164) -3.4 [-5.2, -1.7] Fasting Insulin (pmol/l)** 36 (1,460) -114.6 [-269.1 - -42.0] 6 (93) -118.3 [-173.6 - -107.6] Buchwald H, Avidor Y, Braunwald E, et al. Bariatric Surgery Systematic Review of the Literature and Meta-analysis. Journal of the American Medical Association 2004 Oct 13;292(14).
Bariatric Surgery Systematic Review and Meta-analysi Impact of Bariatric Surgery on Hypertension TOTAL* GASTRIC BYPASS OUTCOME t (n/n) % [95%CI] t (n/n) % [95% CI] Patients Hypertension Resolved 67 (4,805) 61.7 [55.6, 67.8] 20 (2,115) 67.5 [58.4, 76.5] * Total All bariatric procedures including gastric bypass surgery, Vertical Banded Gastroplasty (VBG), Laparoscopic Adjustable Gastric Banding, Biliopancreatic Diversion, and Duodenal Switch. t = number of studies or treatment groups; n = number of patients with this characteristic; N = number of patients evaluated; Hypertension resolved numerator = discontinued treatment or condition disappeared; denominator includes patients evaluated for resolution. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric Surgery A Systematic Review of the Literature and Meta-analysis. Journal of the American Medical Association 2004 Oct 3;292(14).
Bariatric Surgery A Systematic Review and Meta-analysis Impact of Bariatric Surgery on Hyperlipidemia TOTAL* GASTRIC BYPASS OUTCOME t (N) % [95%CI] t (n/n) % [95% CI] % Patients Improved Hyperlipidemia 23 (846/1,019) 79.3 [68.2, 90.5] 6 (125) 96.9 [93.6, 100.0] Hypercholesterolemia 14 (2,051) 71.3 [55.5, 87.0] 5 (439) 94.9 [90.7, 99.1] Hypertriglyceridemia 11 (983) 82.4 [71.1, 93.7] 4 (271) 91.2 [83.6, 98.8] * Patients Improved numerator includes patients described by study authors as having improved by virtue of elimination or reduction in therapy and patients reported to have improved lipid parameters. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric Surgery A Systematic Review of the Literature and Meta-analysis. Journal of the American Medical Association 2004 Oct 13;292(14).
RYGB and Type 2 Diabetes Authors Pories WJ, Swanson MS, MacDonald KG, et al 1995;222:339-350 350 83% of type 2 diabetic subjects euglycaemic up to 14 yrs follow-up
Long-term mortality after gastric bypass surgery Compared long-term mortality among 7,925 US patients undergoing gastric bypass surgery between 1994 and 2002 and the same number of matched controls with severe obesity. Deaths were assessed using the National Death Index at a mean follow-up of 7 years. Adams TD, Gress RE, Smith SC, et al. N Engl J Med 2007;357:753-61.
Long-term mortality after gastric bypass surgery Results At 5 year follow-up, gastric bypass was associated with a 40% reduction in the risk of death from any cause. Disease specific mortality reductions Coronary artery disease 56% Diabetes 92% Adams TD, Gress RE, Smith SC, et al. N Engl J Med 2007;357:753-61.
Laparoscopic Gastric Bypass Surgery and Adjustable Gastric Banding Significantly Decrease the Prevalence of Type 2 Diabetes Mellitus and Pre-Diabetes among Morbidly Obese Multiethnic Adults: Long-Term Outcome Results Nestor de la Cruz- Muñoz, MD, FACS 1 Sarah E. Messiah, Ph.D., M.P.H. 2 Kristopher L. Arheart, Ed.D. 2,3 Gabriela Lopez-Mitnik, M.S. 2 Steven E. Lipshultz, M.D. 2,3 Alan Livingstone, M.D., F.A.C.S. 1 1 DeWitt Daughtry Family Department of Surgery 2 Department of Pediatrics, Division of Pediatric Clinical Research; 3 Department of Epidemiology and Public Health University of Miami Miller School of Medicine Miami, Florida
Methods A retrospective (2002-2010) medical chart analysis of 1,603 adults 77% female 66% Hispanic mean age at surgery 45 yrs Pre- and 6-month, 1-, 2-, and 3-year post surgery comparative means analyses of: weight (kg) -EWL -BMI HbA1c -FPG
Study Sample 377 subjects had T2DM (determined by previous diagnosis and/or medication usage) 107 had a fasting plasma glucose [FPG] 126 mg/dl but were not on medication and were labeled as undiagnosed T2DM 276 were pre-diabetic (FPG=100-125 mg/dl) 843 had a normal FPG pre-surgery
Pre-Surgery Characteristics * Fasting glucose 126 mg/dl and not on medication for T2DM. Fasting glucose 100-125 mg/dl.
Body Mass Index BMI score 30 35 40 45 50 Baseline 6 Months 1 Year 2 Years 3 Years Diabetic Pre Diabetic Undiagnosed Diabetic Normal Glucose 17
Fasting Glucose and Hemoglobin A1c Changes from Pre-Post Surgery * Fasting glucose 126 mg/dl and not on medication for T2DM. Fasting glucose 100-125 mg/dl
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Fasting Glucose mg/dl 80 100 120 140 160 Baseline 6 Months 1 Year 2 Years 3 Years Diabetic Pre Diabetic Undiagnosed Diabetic Normal Glucose 20
Conclusions Bariatric surgery results in significant weight loss and improvement in FPG and HbA1c levels as far as 3-years post-surgery among ethnically-diverse adults. Bariatric surgery is a safe and effective option for weight and chronic disease risk improvements in this demographic.
Laparoscopic Roux-en-Y Gastric Bypass Procedure Reverses the Metabolic Syndrome in Multiethnic Adults N. de la Cruz-Muñoz 1, G. Lopez-Mitnik 2, K.L. Arheart 3, S.E. Lipshultz 2,3, S.E. Messiah 2,3 1Department of Surgery, 2 Department of Pediatrics, 3Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, FL; Retrospective chart analysis 314 adults (82% female, mean age 40.84 years, SD 10.9 years) Pre- and 1-yr post surgery change in MetS status was assessed via generalized estimating equation (GEE) models. MetS prevalence 43% pre to 10% post (P<0.0001) Men 53% pre- to 12% Women 40% pre- to 11% (P<0.0001 for both comparisons). Non-Hispanic blacks (64% to 17%) Hispanics (44% to 12%) Non-Hispanic whites (22% to 7%)
Adjustable Gastric Banding and Conventional Therapy for Type 2 Diabetes A Randomized Controlled Trial Objective To determine if surgically induced weight loss results in better glycemic control and less need for diabetes medications than conventional approaches to weight loss and diabetes control. Dixon JB, et al. JAMA. 2008;299(3):316-323 23
Adjustable Gastric Banding and Conventional Therapy for Type 2 Diabetes A Randomized Controlled Trial Design, Setting, and Participants randomized controlled trial conducted from December 2002 through December 2006 Participants were 60 obese patients (BMI >30 and <40) with recently diagnosed (<2 years) type 2 diabetes. Interventions Conventional diabetes therapy with a focus on weight loss by lifestyle change vs laparoscopic adjustable gastric banding with conventional diabetes care. Dixon JB, et al. JAMA. 2008;299(3):316-323 24
Adjustable Gastric Banding and Conventional Therapy for Type 2 Diabetes A Randomized Controlled Trial Main Outcome Measures Remission of type 2 diabetes (fasting glucose level <126 mg/dl [7.0 mmol/l] and glycated hemoglobin [HbA1c] value <6.2% while taking no glycemic therapy). Secondary measures included weight and components of the metabolic syndrome. Analysis was by intention-to-treat. Dixon JB, et al. JAMA. 2008;299(3):316-323 25
Adjustable Gastric Banding and Conventional Therapy for Type 2 Diabetes A Randomized Controlled Trial Dixon JB, et al. JAMA. 2008;299(3):316-323 26
Adjustable Gastric Banding and Conventional Therapy for Type 2 Diabetes A Randomized Controlled Trial Dixon JB, et al. JAMA. 2008;299(3):316-323 27
Adjustable Gastric Banding and Conventional Therapy for Type 2 Diabetes A Randomized Controlled Trial 73% vs 13% Remission of type 2 diabetes FBG <126 mg/dl and HbA1c value <6.2% while taking no glycemic therapy Dixon JB, et al. JAMA. 2008;299(3):316-323 28
Adjustable Gastric Banding and Conventional Therapy for Type 2 Diabetes A Randomized Controlled Trial Use of Nondiabetes Medication Reduction in use of antihypertensive agents Surgical group (20/29 at baseline and 6/29 at 2 years, P <.001) Conventional-therapy group (15/26 at baseline and at 2 years) (P =.005) Reduction in the use of lipid-lowering medications Surgical group (12/29 at baseline and 4/29 at 2 years, P =.02) Conventional-therapy group (8/26 at baseline and 7/26 at 2 years). Dixon JB, et al. JAMA. 2008;299(3):316-323 29
Adjustable Gastric Banding and Conventional Therapy for Type 2 Diabetes A Randomized Controlled Trial Conclusions superior glycemic control and diabetes remission rates, higher rates of resolution of metabolic syndrome improvements in insulin sensitivity and concentrations of trig and HDL chol degree of weight loss, not the method, appeared to be the major driver of glycemic improvement and diabetes remission Dixon JB, et al. JAMA. 2008;299(3):316-323 30
Treatment of Mild to Moderate Obesity with Laparoscopic Adjustable Gastric Banding or an Intensive Medical Program RCT 80 adults (20-50yo) BMI 30-35kg/m 2 with associated comorbidity Outcome measures were weight change, presence of the metabolic syndrome, and change in quality of life at 2 years O Brien PE, et al. Annals of Internal Medicine. 2006;144 (9)625-633 31
Treatment of Mild to Moderate Obesity with Laparoscopic Adjustable Gastric Banding or an Intensive Medical Program Nonsurgical Program This program centered on the use of behavioral modification, very-low-calorie diet, and pharmacotherapy with education and professional support began with an intensive 6-month period of very-low-calorie diet A physician saw each patient every 2 weeks during the very- low-calorie diet program and every 4 to 6 weeks during the rest of the study. All patients were seen at least every 6 weeks. O Brien PE, et al. Annals of Internal Medicine. 2006;144 (9)625-633 32
Treatment of Mild to Moderate Obesity with Laparoscopic Adjustable Gastric Banding or an Intensive Medical Program % Weight Loss O Brien PE, et al. Annals of Internal Medicine. 2006;144 (9)625-633 33
Treatment of Mild to Moderate Obesity with Laparoscopic Adjustable Gastric Banding or an Intensive Medical Program O Brien PE, et al. Annals of Internal Medicine. 2006;144 (9)625-633 34
Treatment of Mild to Moderate Obesity with Laparoscopic Adjustable Gastric Banding or an Intensive Medical Program O Brien PE, et al. Annals of Internal Medicine. 2006;144 (9)625-633 35
Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes randomized, controlled trial: 60 patients (30-60 yo) BMI 35 a history of at least 5 years of diabetes, HgA1c 7.0% conventional medical therapy vs. gastric bypass or biliopancreatic diversion Primary end point: Rate of diabetes remission at 2 years defined as a fasting glucose level of <100 mg/dl and HgA1c <6.5% in the absence of pharmacologic therapy). Mingrone G, et al. N Engl J Med 2012 366;17 36
Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes Medical Therapy a multidisciplinary team visits at baseline and at 1, 3, 6, 9, 12, and 24 mo reduced overall energy and fat intake (<30% total fat, <10% sat. fat, and high fiber) increased physical exercise ( 30 minutes of brisk walking every day, possibly associated with moderate-intensity aerobic activity twice a week Mingrone G, et al. N Engl J Med 2012 366;17 37
Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes Mingrone G, et al. N Engl J Med 2012 366;17 38
Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes At 2 years, DM remission: in none of medical therapy, 15 of 20 (75%) of gastric bypass and 19 of 20 (95%) of biliopancreatic diversion (P<0.001 for both comparisons). Mingrone G, et al. N Engl J Med 2012 366;17 39
Mingrone G, et al. N Engl J Med 2012 366;17 40
Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes Mingrone G, et al. N Engl J Med 2012 366;17 41
Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes In conclusion, our findings indicate that bariatric surgery, specifically gastric bypass and biliopancreatic diversion, may be more effective than conventional medical therapy in controlling hyperglycemia in severely obese patients with type 2 diabetes. Mingrone G, et al. N Engl J Med 2012 366;17 42
BPD in lean humans Chylomichronemia Diabetes Preop BMI: 22-24 Results: No weight loss No changes in eating behaviour Remission of diabetes Normalization of plasma lipid profile Increase in BMI levels over time (24-26) Mingrone et al. Diabetologia 1992
BPD and Type 2 Diabetes 312 BPD obese patients with type 2 diabetes Fasting glucose fell within normal values in 310/312 pts 10 years after surgery 304/310 patients maintained normal fasting glucose levels
Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes randomized, controlled trial: 150 patients (20-60 yo) BMI 27-43 a history uncontrolled diabetes, HgA1c 7.0% Intensive medical therapy vs. gastric bypass or sleeve gastrectomy Primary end point: proportion of patients with a HgA1c 6.0% 12 months after treatment. Secondary end points: levels of fasting plasma glucose, fasting insulin, lipids, and high-sensitivity C-reactive protein; the homeostasis model assessment of insulin resistance (HOMA-IR) index; weight loss; blood pressure; adverse events; coexisting illnesses; and changes in medications. Schauer P, et al. N Engl J Med 2012 366;17 45
Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes Schauer P, et al. N Engl J Med 2012 366;17 46
Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes Schauer P, et al. N Engl J Med 2012 366;17 47
Schauer P, et al. N Engl J Med 2012 366;17 48
Schauer P, et al. N Engl J Med 2012 49
Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes Conclusions We conclude that bariatric surgery represents a potentially useful strategy for management of uncontrolled diabetes, since it has been shown to eliminate the need for diabetes medications in some patients and to markedly reduce the need for drug treatment in others. In addition, among patients undergoing surgery, cardiovascular risk factors improved, allowing reductions in lipid-lowering and antihypertensive therapies. Schauer P, et al. N Engl J Med 2012 366;17 50
Bariatric Surgery in Non Morbidly Obese Patients 37 Pts BMI 32-35 Resolution in all
Duodenal-Jejunal Bypass (DJB)
Duodeno-Jejunal Bypass R Cohen et.al SOARD, 2007 First in Man Duodenal Jejunal Bypass HbA 1c (%) 9 8 7 6 5 BMI (kg/m2) 3 0 2 9 2 8 2 7 0 1 2 3 4 5 6 7 8 9 Time Post Surgery (month) 0 1 2 3 4 5 6 7 8 9 Time Post Surgery (month)
Other Approaches Ileal Transposition DePaula
First in Man Ileal Transposition & Sleeve Gastrectomy Glycemic Results (18.8 months mean followup) 12 400 A1c 9 6 3 9.0 5.8 Post-Prandial Glucose 300 200 100 269.2 140.7 0 Pre-op Post-op 0 Pre-op Post-op A depaula and A Macedo; US Endocrine Review; Spring 2007: 43-48
First in Man Ileal Transposition & Sleeve Gastrectomy Metabolic Results (Mean weight loss - 24 ± 9%) 500 60 51.3 Triglycerides 375 250 125 269.2 140.7 HDL 45 30 15 38.8 0 Pre-op Post-op 0 Pre-op Post-op A depaula and A Macedo; US Endocrine Review; Spring 2007: 43-48
New Procedure (for the Non-obese) Omentectomy Midgut Entrectomy Leaving the first 40cm of jejunum and the last 260cm of ileum. Sérgio Santoro; Preliminary Report. Adaptive entero-omentectomy: Physiological and evolutionary bases of an auxiliary treatment to type 2 diabetes. Einstein 2004;2(3)193-8
Conclusions Bariatric surgery can put T2DM into remission and can resolve metabolic syndrome in some obese patients Consider bariatric surgery as a treatment option for adults with BMI >35 kg/m 2 and type 2 diabetes and/or metabolic syndrome (some would say earlier rather then later) We may soon be considering surgery in patients with BMI <35 kg/m 2 with uncontrolled DM 63