Disclosure Mechanisms and Use of Bariatric/Metabolic Surgery I am P.I. on the COSMID trial to Treat Type 2 Diabetes (Comparison of Surgery vs . Medicines for Indian Diabetes), David E. Cummings, M.D. funded by Johnson & Johnson University of Washington, VA Puget Sound, Diabetes & Obesity Center of Excellence, Seattle Gastric Banding Roux-en-Y Gastric Bypass (RYGB) Gastric Bypass Reverses Diabetes How does gastric • ~80% full remission of type 2 DM after RYGB – Buchwald meta-analysis 22,094 patients bypass cause type 2 – Schauer, et al. 1,160 patients – Whitgrove, et al. 1,029 patients diabetes remission? – Pories, et al. 608 patients – Buchwald meta-analysis 2 135,246 patients – Many others DE Cummings
Swedish Obese Subjects Study Usual Care ↑ insulin sensitivity with Total Body How does it work? Banding Weight Loss weight loss undoubtedly (%) Gastroplasty plays an important role Gastric Bypass Sjöström L, et al . JAMA 307:56 (2012) Commentary: Cummings DE et al . Years of Follow Up Nature Med 18:358 (2012) Rapid Resolution of Diabetes After RYGB Evidence for Weight-Independent Anti-DM Effects • Fast kinetics of diabetes resolution 35 • Prospective study of 30 1160 RYGB patients • Glucose homeostasis improves more with RYGB % Diabetes 25 Resolved than with equal weight loss from other means • 240 with DM on oral 20 Upon Initial meds and/or insulin, 15 Hospital 80% F/U Poor correlation between amount of weight lost 10 Discharge 5 and DM remission rates after RYGB • 83% DM resolution 0 Overall <5 6-10 >10 Duration of DM Cummings DE, Rubino F. Nature Med (in press) Schauer PR et al, Ann Surg 238:467 Long-Term Follow-Up of Gastric Bypass vs. Gastric Banding Better Improvement in Diabetes After RYGB Than After Equivalent Weight Loss from Other Means Percentage Weight Loss Percentage With Diabetes • RYGB vs . LAGB – LeRoux C, et al; Pattou F, et al Band % With Diabetes % Weight Loss • RYGB vs . Dietary Weight Loss – LaFerrere B, et al; Meirelles K, et al Band Bypass • Sleeve Gastrectomy with Proximal Intestinal Bypass vs . Bypass Sleeve Gastrectomy Alone – Lee WJ, et al Time (months) Time (months) C. le Roux, et al DE Cummings Ann Surg 252:966 (2010)
Evidence for Weight-Independent Anti-DM Effects A Long-Term Study of • Fast kinetics of diabetes resolution • Glucose homeostasis improves more with RYGB RYGB to Treat Type 2 than with equal weight loss from other means Diabetes in Patients • Inconsistent correlation after RYGB between baseline weight or amount of weight loss and With Only Mild Obesity rates of DM remission, prevention, & recurrence, as well as hard clinical outcomes Cummings DE, Rubino F. Nature Med (in press) Cohen RV….Cummings DE. Diabetes Care 35:1420 (2012) Rapid & Durable Improvement in HbA1c After RYGB in BMI 30-35 Prospective Study of RYGB for Type 2 DM A in Patients With BMI 30–35 kg/m 2 11 • 66 patients with diabetes 10 100% F/U to 6 yrs – 100% F/U up to 6 years 9 • BMI 30–35 kg/m 2 Hemoglobin – Mild obesity for this population A1c 8 (%) • Type 2 DM 7 – Confirmed with Abs, C-peptide, FHx • Severe diabetes 6 – Mean duration: 13 years Cohen RV….. Cohen RV….. – 40% on insulin (the rest on oral DM meds) 5 Cummings DE Cummings DE 0 0.5 1 2 4 5 6 – HbA1c: 9.7% at start Diabetes Care Diabetes Care Years After Surgery 35:1420 (2012) 35:1420 (2012) Diabetes Remission in 6-Year Study of RYGB 140 0 Resolved -5 130 For Type 2 DM in Patients With BMI 30–35 kg/m 2 -10 -15 120 Waist -20 Total Body Circumference 110 -25 70 Weight Loss (cm) -30 (%) 100 88% -35 60 -40 90 -45 80 50 -50 0 6 12 24 48 60 72 0 6 12 24 48 60 72 Number 40 140 0 Of -5 Improved Patients 30 130 -10 -15 120 Waist 20 -20 Total Body Circumference 110 -25 Weight Loss 11% -30 10 (cm) 100 (%) 1% -35 -40 90 Cohen RV….. 0 Cohen RV….. -45 Cummings DE T2DM T2DM No 80 -50 Cummings DE 0 6 12 24 48 60 72 0 6 12 24 48 60 72 Diabetes Care Remission Improvement Change Diabetes Care Months After Surgery Months After Surgery 35:1420 (2012) 35:1420 (2012)
Do Changes in BMI Correlate With Changes in Glycemia? No Relationship Between Change in BMI and Change in HbA1c at 6 Months A 11 7 ∆ BMI vs . ∆ Glycemia 6 10 Regression Analyses 5 9 Hemoglobin Change 4 In A1c 8 3 HbA1c (%) 7 2 1 6 0 Cohen RV….. 2.0 4.0 6.0 8.0 10.0 12.0 Cohen RV….. 5 Cummings DE 0 0.5 1 2 4 5 6 Cummings DE Diabetes Care Change in BMI (kg/m2) Diabetes Care Years After Surgery 35:1420 (2012) 35:1420 (2012) No Relationship Between Change in BMI and Change in FPG at 6 Months No Relationship Between Change in BMI and Change in HbA1c at 1 Year 7 140 6 120 100 5 Change 80 In Change 4 60 In Fasting 3 HbA1c Plasma 40 Glucose 20 2 0 1 2.0 4.0 6.0 8.0 10.0 12.0 -20 0 -40 7.0 9.0 11.0 13.0 15.0 Cohen RV….. Cohen RV….. Cummings DE Cummings DE Change in BMI (kg/m2) Change in BMI (kg/m2) Diabetes Care Diabetes Care 35:1420 (2012) 35:1420 (2012) No Relationship Between Change in BMI and Change in FPG at 1 Year Lack of Correlation Between Weight Loss and Improved Glycemia 160 3 mo 6 mo 1 year 2 years 4 years 5 years 6 years 140 120 Correl Change 0.065 0.001 0.195 0.097 0.081 0.003 0.016 100 HbA1c Coeff In 80 Fasting Plasma 60 P ‐ Value 0.60 0.99 0.12 0.47 0.59 0.99 0.93 Glucose 40 Fasting Glu 20 Correl 0.130 0.170 0.136 0.023 0.240 0.541 0.431 Coeff 0 7.0 9.0 11.0 13.0 15.0 -20 Cohen RV….. P ‐ Value 0.30 0.17 0.28 0.86 0.10 0.001 0.017 Cummings DE Change in BMI (kg/m2) Diabetes Care 35:1420 (2012)
Tests of Beta-Cell Function Long After RYGB A 11 C-Peptide Testing 10 Effects on With Standardized Meal 9 Hemoglobin A1c 8 Insulin Secretion (%) 7 6 Cohen RV….. 5 Cummings DE 0 0.5 1 2 4 5 6 Diabetes Care Years After Surgery 35:1420 (2012) Improved β –Cell Function for Up to 6 Years After RYGB 250 200 Effects on 150 * Glucose * (mg/dL) 100 50 Roughly Estimated Before RYGB 0 After RYGB 6 * 5 ↑ β -cell Insulin Sensitivity C-Peptide 4 3 (ng/mL) sensitivity 2 to glucose Cohen RV….. 1 Cummings DE by 446% 0 Diabetes Care Fasting Post-Meal 35:1420 (2012) Change in Roughly Estimated Insulin Resistance After RYGB 12 10 Effects on Metabolic 8 Syndrome and HOMA-IR 6 4 Predicted CVD Risk 2 Cohen RV….. 0 Cummings DE 0 1 2 3 4 5 6 Diabetes Care Years After Surgery 35:1420 (2012)
160 1 4 0 220 140 Low 130 1 3 5 200 120 Density 180 110 1 3 0 Systolic Blood Total Lipoprotein 160 100 Pressure (mmHg) Cholesterol (mg/dL) 1 2 5 90 140 (mg/dL) 80 120 1 2 0 70 100 60 1 1 5 55 230 90 210 50 High 190 45 85 Density 170 40 Triglycerides Diastolic Blood Lipoprotein 150 Pressure (mmHg) 80 (mg/dL) 35 (mg/dL) 130 30 110 75 25 90 20 70 Cohen RV….. 70 0 0.5 1 2 4 5 6 0 0.5 1 2 4 5 6 Cohen RV….. Cummings DE 0 0.5 1 2 4 5 6 Cummings DE Diabetes Care Years After Surgery Years After Surgery Years After Surgery Diabetes Care 35:1420 (2012) 35:1420 (2012) Asian Indians Have Increased 10-Year Cardiovascular Risk Diabetes Risk at Lower BMI Levels Before vs . After RYGB Asian Diabetes Incidence per 1000 person-years Indian Pre-Surgery Post-Surgery Relative Chiu M et al. Diabetes Cardio- Absolute 95% (n=66) (n=66) Care 34:1741, 2011 Vascular Risk Confidence Risk P Value Chinese Mean Risk Mean Risk Event Reduction Interval Reduction Black (%) ± SD (%) ± SD 35.3 ± 10.0 10.3 ± 2.6 71% CHD 25% 8.2–13.3 0.001 White 26.2 ± 8.1 5.4 ± 1.9 84% Fatal CHD 21% 3.7–8.0 0.001 5.0 ± 0.4 2.5 ± 1.7 Stroke 50% 0.01 2.5% 1.7–6.0 0.7 ± 0.3 0.4 ± 0.2 Fatal Stroke 0.3% 0.03–0.1 57% 0.009 Cohen RV….Cummings DE. Diabetes Care 35:1420 (2012) Body Mass Index (kg/m2) Prospective Study of RYGB for Type 2 DM BMI & Diabetes in Taiwan NTUH in Asian Indians With BMI < 35 kg/m 2 350 • BMI 22–35 kg/m 2 300 – “Overweight” to “Obese” by Indian-specific 250 WHO criteria Number 200 • Type 2 DM 2,555 cases 150 – Confirmed with Abs, C-peptide, FHx 100 • Severe diabetes 50 – Mean duration: 9 years – 80% on insulin (the rest on oral DM meds) 0 – HbA1c: 10.1% 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 • Other features Shah S, BMI 27–30 30–35 >35 Todkar J….. – Dyslipidemia: 93% Cummings DE 17% 9% <2% WJ Lei, et al . – Hypertension: 60% SOARD 6:332 J Gastrointest Surg 12:945
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