Leaque Ahmed

Roux-en-Y gastric bypass vs intensive medical management for the control of type 2 diabetes, hypertension, and hyperlipidemia: the Diabetes Surgery Study randomized clinical trial.

IMPORTANCE Controlling glycemia, blood pressure, and cholesterol is important for patients with diabetes. How best to achieve this goal is unknown. OBJECTIVE To compare Roux-en-Y gastric bypass with lifestyle and intensive medical management to achieve control of comorbid risk factors. DESIGN, SETTING, AND PARTICIPANTS A 12-month, 2-group unblinded randomized trial at 4 teaching hospitals in the United States and Taiwan involving 120 participants who had a hemoglobin A1c (HbA1c) level of 8.0% or higher, body mass index (BMI) between 30.0 and 39.9, C peptide level of more than 1.0 ng/mL, and type 2 diabetes for at least 6 months. The study began in April 2008. INTERVENTIONS Lifestyle-intensive medical management intervention and Roux-en-Y gastric bypass surgery. Medications for hyperglycemia, hypertension, and dyslipidemia were prescribed according to protocol and surgical techniques that were standardized. MAIN OUTCOMES AND MEASURES Composite goal of HbA1c less than 7.0%, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood pressure less than 130 mm Hg. RESULTS All 120 patients received the intensive lifestyle-medical management protocol and 60 were randomly assigned to undergo Roux-en-Y gastric bypass. After 12-months, 28 participants (49%; 95% CI, 36%-63%) in the gastric bypass group and 11 (19%; 95% CI, 10%-32%) in the lifestyle-medical management group achieved the primary end points (odds ratio [OR], 4.8; 95% CI, 1.9-11.7). Participants in the gastric bypass group required 3.0 fewer medications (mean, 1.7 vs 4.8; 95% CI for the difference, 2.3-3.6) and lost 26.1% vs 7.9% of their initial body weigh compared with the lifestyle-medical management group (difference, 17.5%; 95% CI, 14.2%-20.7%). Regression analyses indicated that achieving the composite end point was primarily attributable to weight loss. There were 22 serious adverse events in the gastric bypass group, including 1 cardiovascular event, and 15 in the lifestyle-medical management group. There were 4 perioperative complications and 6 late postoperative complications. The gastric bypass group experienced more nutritional deficiency than the lifestyle-medical management group. CONCLUSIONS AND RELEVANCE In mild to moderately obese patients with type 2 diabetes, adding gastric bypass surgery to lifestyle and medical management was associated with a greater likelihood of achieving the composite goal. Potential benefits of adding gastric bypass surgery to the best lifestyle and medical management strategies of diabetes must be weighed against the risk of serious adverse events. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00641251.

Very Low–Calorie Diet Mimics the Early Beneficial Effect of Roux-en-Y Gastric Bypass on Insulin Sensitivity and β-Cell Function in Type 2 Diabetic Patients

Marked improvement in glycemic control occurs in patients with type 2 diabetes mellitus shortly after Roux-en-Y gastric bypass surgery (RYGB) and before there is major weight loss. The objective of this study was to determine whether the magnitude of this change is primarily due to caloric restriction or is unique to the surgical procedure. We studied eleven subjects who underwent RYGB and fourteen subjects mean-matched for BMI, HbA1c, and diabetes duration who were admitted to our inpatient research unit and given a very low–calorie diet (VLCD) of 500 kcal/day with a macronutrient content similar to that consumed by patients after RYGB. Frequently sampled intravenous glucose tolerance tests were performed before and after interventions. Both groups lost an equivalent amount of weight over a mean study period of 21 days. Insulin sensitivity, acute insulin secretion after intravenous glucose administration, and β-cell function as determined by disposition index improved to a similar extent in both groups. Likewise, changes in fasting glucose and fructosamine levels were similar. Based on these data, VLCD improves insulin sensitivity and β-cell function just as well as RYGB in the short term.

Comparison of Glucostatic Parameters After Hypocaloric Diet or Bariatric Surgery and Equivalent Weight Loss

Weight‐loss independent mechanisms may play an important role in the improvement of glucose homeostasis after Roux‐en‐Y gastric bypass (RYGB). The objective of this analysis was to determine whether RYGB causes greater improvement in glucostatic parameters as compared with laparoscopic adjustable gastric banding (LAGB) or low calorie diet (LCD) after equivalent weight loss and independent of enteral nutrient passage. Study 1 recruited participants without type 2 diabetes mellitus (T2DM) who underwent LAGB (n = 8) or RYGB (n = 9). Study 2 recruited subjects with T2DM who underwent LCD (n = 7) or RYGB (n = 7). Insulin‐supplemented frequently‐sampled intravenous glucose tolerance test (fsIVGTT) was performed before and after equivalent weight reduction. MINMOD analysis of insulin sensitivity (Si), acute insulin response to glucose (AIRg) and C‐peptide (ACPRg) response to glucose, and insulin secretion normalized to the degree of insulin resistance (disposition index (DI)) were analyzed. Weight loss was comparable in all groups (7.8 ± 0.4%). In Study 1, significant improvement of Si, ACPRg, and DI were observed only after LAGB. In Study 2, Si, ACPRg, and plasma adiponectin increased significantly in the RYGB‐DM group but not in LCD. DI improved in both T2DM groups, but the absolute increase was greater after RYGB (258.2 ± 86.6 vs. 55.9 ± 19.9; P < 0.05). Antidiabetic medications were discontinued after RYGB contrasting with 55% reduction in the number of medications after LCD. No intervention affected fasting glucagon‐like peptide (GLP)‐1, peptide YY (PYY) or ghrelin levels. In conclusion, RYGB produced greater improvement in Si and DI compared with diet at equivalent weight loss in T2DM subjects. Such a beneficial effect was not observed in nondiabetic subjects at this early time‐point.

Better preservation of endocrine function after central versus distal pancreatectomy for mid-gland lesions.

BACKGROUND Traditional resections for benign and low-grade malignant neoplasms of the mid pancreas result in loss of normal parenchyma that can cause pancreatic endocrine and exocrine insufficiency. Central pancreatectomy (CP) is a parenchyma-sparing option for such lesions. This study evaluates a single institutions experience with CP and compares outcomes with distal pancreatectomy (DP). METHODS We retrospectively collected data on CP patients from 1997 through 2009 and evaluated outcomes. In a subset of 50 patients, we performed a matched-pairs analysis to directly compare the short- and long-term outcomes of CP and DP. RESULTS Seventy-three patients underwent CP with a median operating room time of 254 minutes. Overall morbidity was 41.1% with pancreatic fistula in 20.5%. Mortality was 0%. There were no differences in fistula, morbidity, and mortality rates between the CP and DP groups. The CP group had resected for smaller lesions. CP patients had a lower rate of new-onset and worsening diabetes than DP patients (14% vs 46%; P = .003). Of new-onset and worsening diabetics, only 1 CP patient required insulin compared with 14 DP patients (P = .002). CONCLUSION CP is safe and effective for select neoplasms of the mid pancreas. Patients undergoing CP have markedly decreased insulin requirements compared with DP patients.

Durability of Addition of Roux-en-Y Gastric Bypass to Lifestyle Intervention and Medical Management in Achieving Primary Treatment Goals for Uncontrolled Type 2 Diabetes in Mild-to-Moderate Obesity: A Randomized Control Trial

OBJECTIVE We compared 3-year achievement of an American Diabetes Association composite treatment goal (HbA1c <7.0%, LDL cholesterol <100 mg/dL, and systolic blood pressure <130 mmHg) after 2 years of intensive lifestyle-medical management intervention, with and without Roux-en-Y gastric bypass, with one additional year of usual care. RESEARCH DESIGN AND METHODS A total of 120 adult participants, with BMI 30.0–39.9 kg/m2 and HbA1c ≥8.0%, were randomized 1:1 to two treatment arms at three clinical sites in the U.S. and one in Taiwan. All patients received the lifestyle-medical management intervention for 24 months; half were randomized to also receive gastric bypass. RESULTS At 36 months, the triple end point goal was met in 9% of lifestyle-medical management patients and 28% of gastric bypass patients (P = 0.01): 10% and 19% lower than at 12 months. Mean (SD) HbA1c values at 3 years were 8.6% (3.5) and 6.7% (2.0) (P < 0.001). No lifestyle-medical management patient had remission of diabetes at 36 months, whereas 17% of gastric bypass patients had full remission and 19% had partial remission. Lifestyle-medical management patients used more medications than gastric bypass patients: mean (SD) 3.8 (3.3) vs. 1.8 (2.4). Percent weight loss was mean (SD) 6.3% (16.1) in lifestyle-medical management vs. 21.0% (14.5) in gastric bypass (P < 0.001). Over 3 years, 24 serious or clinically significant adverse events were observed in lifestyle-medical management vs. 51 with gastric bypass. CONCLUSIONS Gastric bypass is more effective than lifestyle-medical management intervention in achieving diabetes treatment goals, mainly by improved glycemic control. However, the effect of surgery diminishes with time and is associated with more adverse events.

The utility of [11C] dihydrotetrabenazine positron emission tomography scanning in assessing β-cell performance after sleeve gastrectomy and duodenal-jejunal bypass

BACKGROUND The aim of this study was to evaluate the effect of sleeve gastrectomy (SG) and duodenal-jejunal bypass (DJB) on glucose homeostasis and to evaluate the utility of positron emission tomography (PET) scanning for assessing beta-cell mass. METHODS Goto-Kakizaki rats were divided into 4 groups: control, sham, SG, or DJB. Oral glucose tolerance, insulin, and glucagon-like peptide-1 (GLP-1) were measured before and after surgery. Before and 90 days after treatment, [(11)C] DTBZ micro PET scanning was performed. RESULTS The control and sham animals gained more weight compared with SG and DJB animals (P < or = .05). Compared with control animals, the glucose area under the curve was lower in DJB animals 30 and 45 days after operations (P < or = .05). At killing, GLP-1 levels were greater in the DJB group compared with sham and SG (P < or = .05), whereas insulin levels were greater in both DJB and SG compared with sham (P < or = .05). With PET scanning, the 90-day posttreatment mean vesicular monoamine transporter type 2 binding index was greatest in the DJB animals (2.45) compared with SG (1.17), both of which were greater than baseline control animals (0.81). CONCLUSION In type 2 diabetic rodents, DJB leads to improved glucose homeostasis and an increase in VMAT2 density as measured by PET scanning.

Preserved Insulin Secretory Capacity and Weight Loss Are the Predominant Predictors of Glycemic Control in Patients With Type 2 Diabetes Randomized to Roux-en-Y Gastric Bypass

Improvement in type 2 diabetes after Roux-en-Y gastric bypass (RYGB) has been attributed partly to weight loss, but mechanisms beyond weight loss remain unclear. We performed an ancillary study to the Diabetes Surgery Study to assess changes in incretins, insulin sensitivity, and secretion 1 year after randomization to lifestyle modification and intensive medical management (LS/IMM) alone (n = 34) or in conjunction with RYGB (n = 34). The RYGB group lost more weight and had greater improvement in HbA1c. Fasting glucose was lower after RYGB than after LS/IMM, although the glucose area under the curve decreased comparably for both groups. Insulin sensitivity increased in both groups. Insulin secretion was unchanged after LS/IMM but decreased after RYGB, except for a rapid increase during the first 30 min after meal ingestion. Glucagon-like peptide 1 (GLP-1) was substantially increased after RYGB, while gastric inhibitory polypeptide and glucagon decreased. Lower HbA1c was most strongly correlated with the percentage of weight loss for both groups. At baseline, a greater C-peptide index and 90-min postprandial C-peptide level were predictive of lower HbA1c at 1 year after RYGB. β-Cell glucose sensitivity, which improved only after RYGB, and improved disposition index were associated with lower HbA1c in both groups, independent of weight loss. Weight loss and preserved β-cell function both predominantly determine the greatest glycemic benefit after RYGB.

Jejunal Bezoar causing obstruction after laparoscopic Roux-en-Y gastric bypass.

The authors report on 2 patients who had small bowel obstruction secondary to phytobezoars following Roux-en-Y gastric bypass.

The effect of bariatric surgery on renal function

BACKGROUND Obesity is associated with albuminuria and impaired renal function. We previously reported on 38 nondiabetics with improved albuminuria after Roux-en-Y gastric bypass (RYGB). METHODS Our objectives were to evaluate changes in renal function, urinary albumin-to-creatinine ratio (UACR), and glomerular filtration rate (GFR) in a larger cohort of patients with normal or mildly impaired renal function, undergoing RYGB or sleeve gastrectomy at 1 year postop. This was a retrospective study. Inclusions: patients with preoperative and 1 year postoperative serum and urine albumin and creatinine and weight (kg). EXCLUSIONS preop chronic kidney disease (CKD)≥Stage 3 or macroalbuminuria (UACR≥300 mg/g). PRIMARY OUTCOMES changes in UACR and estimated GFR (eGFR) at 1 year. The setting was in a public hospital in New York City, 2004-2011. RESULTS 158 patients met inclusion criteria; 91.8% female; mean age 40.8 years; 84.2% white Hispanic, 14.6 % black. Hypertension was present in 43.0%, diabetes mellitus in 28.5%. UACR was 21.5±3.2 mg/g, decreasing to 10.2±1.2 mg/g at 1 year (P<.0001). Microalbuminuria was present in 22/158 patients (14%) preop, resolving in 82% at 1 year; pre- versus 1 year postop eGFR, 97.5±2.2 versus 87.1±2.0 mL/min (P<.0001). Hyperfiltration was present in 8.2% preop, decreasing to 4.4% 1 year postop. CONCLUSION In this mainly female minority population, UACR decreased within the normal range, while eGFR decreased from normal to the range for Stage 2 CKD at 1 year postop. Microalbuminuria resolved in most affected and hyperfiltration resolved in nearly half of those affected. This study is limited by its retrospective nature. Prospective studies should be performed.

Lifestyle Intervention and Medical Management With vs Without Roux-en-Y Gastric Bypass and Control of Hemoglobin A1c, LDL Cholesterol, and Systolic Blood Pressure at 5 Years in the Diabetes Surgery Study

Importance The Roux-en-Y gastric bypass is effective in achieving established diabetes treatment targets, but durability is unknown. Objective To compare durability of Roux-en-Y gastric bypass added to intensive lifestyle and medical management in achieving diabetes control targets. Design, Setting, and Participants Observational follow-up of a randomized clinical trial at 4 sites in the United States and Taiwan, involving 120 participants who had a hemoglobin A1c (HbA1c) level of 8.0% or higher and a body mass index between 30.0 and 39.9 (enrolled between April 2008 and December 2011) were followed up for 5 years, ending in November 2016. Interventions Lifestyle-intensive medical management intervention based on the Diabetes Prevention Program and LookAHEAD trials for 2 years, with and without (60 participants each) Roux-en-Y gastric bypass surgery followed by observation to year 5. Main Outcomes and Measures The American Diabetes Association composite triple end point of hemoglobin A1c less than 7.0%, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood pressure less than 130 mm Hg at 5 years. Results Of 120 participants who were initially randomized (mean age, 49 years [SD, 8 years], 72 women [60%]), 98 (82%) completed 5 years of follow-up. Baseline characteristics were similar between groups: mean (SD) body mass index 34.4 (3.2) for the lifestyle–medical management group and 34.9 (3.0) for the gastric bypass group and had hemoglobin A1c levels of 9.6% (1.2) and 9.6% (1.0), respectively. At 5 years, 13 participants (23%) in the gastric bypass group and 2 (4%) in the lifestyle-intensive medical management group had achieved the composite triple end point (difference, 19%; 95% CI, 4%-34%; P = .01). In the fifth year, 31 patients (55%) in the gastric bypass group vs 8 (14%) in the lifestyle–medical management group achieved an HbA1c level of less than 7.0% (difference, 41%; 95% CI, 19%-63%; P = .002). Gastric bypass had more serious adverse events than did the lifestyle–medical management intervention, 66 events vs 38 events, most frequently gastrointestinal events and surgical complications such as strictures, small bowel obstructions, and leaks. Gastric bypass had more parathyroid hormone elevation but no difference in B12 deficiency. Conclusions and Relevance In extended follow-up of obese adults with type 2 diabetes randomized to adding gastric bypass compared with lifestyle and intensive medical management alone, there remained a significantly better composite triple end point in the surgical group at 5 years. However, because the effect size diminished over 5 years, further follow-up is needed to understand the durability of the improvement. Trial Registration clinicaltrials.gov Identifier: NCT00641251