Keong Chong

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.

Gastric bypass vs sleeve gastrectomy for type 2 diabetes mellitus: a randomized controlled trial.

OBJECTIVES To determine the efficacies of 2 weight-reducing operations on diabetic control and the role of duodenum exclusion. DESIGN Double-blind randomized controlled trial. SETTING Department of Surgery of the Min-Sheng General Hospital, National Taiwan University. PATIENTS We studied 60 moderately obese patients (body mass index >25 and <35) aged >30 to <60 years who had poorly controlled type 2 diabetes mellitus (T2DM) (hemoglobin A(1c) [HbA(1c)] >7.5%) after conventional treatment (>6 months) from September 1, 2007, through June 30, 2008. Patients and observers were masked during the follow-up, which ended in 2009, 1 year after final enrollment. INTERVENTIONS Gastric bypass with duodenum exclusion (n = 30) vs sleeve gastrectomy without duodenum exclusion (n = 30). MAIN OUTCOME MEASURES The primary outcome was remission of T2DM (fasting glucose <126 mg/dL and HbA(1c) <6.5% without glycemic therapy). Secondary measures included weight and metabolic syndrome. Analysis was by intention to treat. RESULTS Of the 60 patients enrolled, all completed the 12-month follow-up. Remission of T2DM was achieved by 28 (93%) in the gastric bypass group and 14 (47%) in the sleeve gastrectomy group (P = .02). Participants assigned to gastric bypass had lost more weight, achieved a lower waist circumference, and had lower glucose, HbA(1c), and blood lipid levels than the sleeve gastrectomy group. No serious complications occurred in either group. CONCLUSIONS Participants randomized to gastric bypass were more likely to achieve remission of T2DM. Duodenum exclusion plays a role in T2DM treatment and should be assessed. Trial Registration clinicaltrials.gov Identifier: NCT00540462 (http://www.clinicaltrials.gov).

Predicting the Glycemic Response to Gastric Bypass Surgery in Patients With Type 2 Diabetes

OBJECTIVE To find clinically meaningful preoperative predictors of diabetes remission and conversely inadequate glycemic control after gastric bypass surgery. Predicting the improvement in glycemic control in those with type 2 diabetes after bariatric surgery may help in patient selection. RESEARCH DESIGN AND METHODS Preoperative details of 154 ethnic Chinese subjects with type 2 diabetes were examined for their influence on glycemic outcomes at 1 year after gastric bypass. Remission was defined as HbA1c ≤6%. Analysis involved binary logistic regression to identify predictors and provide regression equations and receiver operating characteristic curves to determine clinically useful cutoff values. RESULTS Remission was achieved in 107 subjects (69.5%) at 12 months. Diabetes duration <4 years, body mass >35 kg/m2, and fasting C-peptide concentration >2.9 ng/mL provided three independent preoperative predictors and three clinically useful cutoffs. The regression equation classification plot derived from continuous data correctly assigned 84% of participants. A combination of two or three of these predictors allows a sensitivity of 82% and specificity of 87% for remission. Duration of diabetes (with different cutoff points) and C-peptide also predicted those cases in which HbA1c ≤7% was not attained. Percentage weight loss after surgery was also predictive of remission and of less satisfactory outcomes. CONCLUSIONS The glycemic response to gastric bypass is related to BMI, duration of diabetes, fasting C-peptide (influenced by insulin resistance and residual β-cell function), and weight loss. These data support and refine previous findings in non-Asian populations. Specific ethnic and procedural regression equations and cutoff points may vary.

Laparoscopic sleeve gastrectomy for diabetes treatment in nonmorbidly obese patients: Efficacy and change of insulin secretion

BACKGROUND Sleeve gastrectomy is a new bariatric surgery, and many reports have showed that patients who have undergone sleeve gastrectomy have experienced rapid resolution of type 2 diabetes. The mechanisms accounting for the beneficial effects of sleeve gastrectomy on glucose homeostasis are not well understood and remain speculative. This trial assessed prospectively the effect of sleeve gastrectomy on type 2 diabetes and the serial changes of insulin secretion to oral glucose loads. METHODS Prospective study on the response of insulin secretion to oral glucose loads in 20 severe diabetic patients (body mass index [BMI] >25 and <35, HbA1C >7.5%) before and at 1, 4, 12, 26, and 52 weeks after sleeve gastrectomy. The insulin secretion was measured by insulinogenic index and area under the curve (AUC) during a standard oral glucose tolerance test (OGTT). Remission of type 2 diabetes was defined as fasting glucose level <126 mg/dL and HbA1C <6.5% without any glycemic therapy. RESULTS Of the 20 patients enrolled, the mean age was 46.3 + or - 8.0 years, mean BMI was 31.0 + or - 2.9 kg/m(2), and mean HbA1C was 10.1 + or - 2.2. The mean BMI and excess body weight loss at 1, 4, 12, 26, and 52 weeks after operation were 28.9 (22.1%), 27.4 (43.0%), 25.7 (55.1%), 24.9 (71.9%), and 24.6 (69.1%), respectively. The mean HbA1C at 1, 4, 12, 26, and 52 weeks after operation were 9.2, 8.4, 7.7, 7.3, and 7.1, respectively. Resolution of type 2 diabetes was achieved in 2 (20%) patients at 4 weeks, 6 (30%) at 12 weeks, 8 (40%) at 26 weeks, and 10 (50%) at 52 weeks after sleeve gastrectomy. Before operation, the mean fasting plasma glucose and insulin levels were 240.1 + 80.9 mg/dL and 16.8 + or - 15.4 uIU/mL, respectively. The OGTT test showed a blunted insulin secretion pattern with an AUC of 3,135 uIU x min/mL. At 1 week after operation, the fasting plasma glucose and insulin levels significantly decreased to 158 + or - 52 mg/dL and 5.6 + or - 3.2 uIU/mL, respectively. The AUC decreased to 2,988.7 uIU x min/mL. The AUC at 4, 12, 26, and 52 weeks after operation was 2,211, 1,584, 3,621, and 3,351 uIU x min/mL, respectively. The diabetes resolution rates for those with pre-operative C-peptide <3, 3-6, and >6 ng/mL were 1/7 (14.3%), 7/11 (63.6%), and 2/2 (100%), respectively (P < .05). CONCLUSION Laparosopic gastric sleeve gastrectomy resulted in remission of poorly controlled nonmorbidly obese T2DM patients up to 50% at 1 year after operation. The effect is related more to the decreasing of insulin resistance because of calorie restriction and weight loss rather than to the increasing of insulin secretion. C-peptide >3 ng/mL is the most important predictor for a successful treatment.

Changes in postprandial gut hormones after metabolic surgery: a comparison of gastric bypass and sleeve gastrectomy.

BACKGROUND Laparoscopic gastric bypass (GB) is reportedly more effective than laparoscopic sleeve gastrectomy (SG) in the treatment of patients with a low body mass index and type 2 diabetes mellitus. However, the mechanism remains speculative. We compared the postprandial gut hormone patterns between patients undergoing laparoscopic GB and laparoscopic SG at 2 years after surgery in a hospital-based, prospective study. METHODS A total of 16 laparoscopic GB and 16 laparoscopic SG patients were followed up and appraised for glucose homeostasis. Two years after surgery, the mixed meal test and gut hormones were evaluated in 13 laparoscopic GB and 13 laparoscopic SG patients who had been included in the previous randomized trial. RESULTS The preoperative characteristics, such as body mass index, body weight, waist circumference, and duration of T2DM were comparable between the 2 groups. T2DM remission was achieved in 13 (81%) laparoscopic GB and 3 (19%) laparoscopic SG patients (P < .05) 2 years after surgery. The laparoscopic GB patients had lost more weight and had a smaller waist circumference and lower levels of glucose and hemoglobin A1c, and lower insulin resistance than the SG patients. Significant differences were found in acyl ghrelin, des-acyl ghrelin, cholecystokinin, and resistin between the 2 groups, but none in obestatin, gastric inhibitory peptide, glucagon-like peptide-1, and leptin. CONCLUSIONS Both laparoscopic GB and laparoscopic SG have strong hindgut effects after surgery, but GB has a significant duodenal exclusion effect on cholecystokinin. The laparoscopic SG group had lower acyl ghrelin and des-acyl ghrelin levels but greater concentrations of resistin than the laparoscopic GB group.

Gastric bypass in Type 2 diabetes with BMI < 30: weight and weight loss have a major influence on outcomes

To assess factors influencing glycaemic control following gastric bypass surgery in patients with Type 2 diabetes and BMI< 30 kg/m2.

Predictors of diabetes remission after bariatric surgery in Asia

BACKGROUND Obesity and type II diabetes mellitus (T2DM) are closely related and difficult to control by current medical treatment. Bariatric surgery has been proposed for inadequately controlled T2DM in association with obesity. However, prediction of successful T2DM remission after surgery has not been clearly studied in Asian patients. This information might be helpful for applying gastrointestinal surgery as metabolic surgery for T2DM. METHODS This was a retrospective clinical study. From January 2002 to December 2008, 88 consecutive patients with morbid obesity, who were enrolled into a surgically supervised weight loss program, and who had T2DM before surgery with at least 1 year complete follow-up data were included. Sixty-eight (77.2%) patients received gastric bypass procedures, and the remaining 20 (22.8%) received restrictive procedures. We analyzed the available information during the initial evaluation of patients who were referred for bariatric surgery, by logistic regression analysis and data mining methods for predictors of successful diabetes remission after surgery. RESULTS Overall, 68 (77.2%) of the 88 patients had remission of their T2DM 1 year after surgery. Patients in the bypass group had a higher remission rate than those in the restrictive group [59/68 (86.7%) vs. 9/20 (45.0%), p=0.000]. In univariate analysis, patients who had T2DM remission after surgery were younger, heavier, had a wider waist, less severe disease, shorter duration, and higher C-peptide levels than those without remission. Type of operation and T2DM duration remained independent predictors of success after multivariate logistical regression analysis (p<0.000). Data mining analysis confirmed that T2DM duration was the most important predictor. CONCLUSIONS Bariatric surgery is a treatment option for T2DM. Duration of diabetes is the most predictor of success after surgery.

Differential Influences of Gastric Bypass and Sleeve Gastrectomy on Plasma Nesfatin-1 and Obestatin Levels in Patients with Type 2 Diabetes Mellitus

OBJECTIVE The mechanisms by which bariatric surgeries, including gastric bypass (GB) and sleeve gastrectomy (SG), achieve remission of type 2 diabetes mellitus (T2DM) and sustained weight reduction are unknown. We hypothesized that the novel anorexic hormone nesfatin-1 and another new hormone obestatin might contribute to the marked improvement in glycemic homeostasis and weight loss in diabetics after GB and SG. METHODS A hospital-based, prospective study was conducted. Overnight fasting plasma concentrations of nesfatin-1 and obestatin were analyzed in T2DM patients before surgery, and at 3 and 12 months after laparoscopic GB (n =12) and SG (n = 6). RESULTS At 12 months, reductions of body mass index (BMI), fasting blood glucose, and glycated hemoglobin were similar between GB and SG groups (P all > 0.05). Plasma nesfatin-1 levels in patients undergoing GB or SG significantly decreased after surgeries (P both < 0.05). In contrast, plasma obestatin concentrations significantly increased in patients after SG (P < 0.05) but without any alteration after GB. The alterations of plasma nesfatin-1 were significantly and negatively associated with the reduction of fasting blood glucose (P <0.05) at 12 months after GB and SG. In the SG group, the reduction of nesfatin-1 significantly and positively correlated with the decrease of BMI (P < 0.05). CONCLUSIONS GB and SG produce differential influences with regards to circulating nesfatin-1 and obestatin levels in non-morbidly obese, T2DM patients. Circulating nesfatin-1 may modulate glucose homeostasis in two surgical procedures, and participate in regulating body weight in SG.

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.

Insulin Secretion and Interleukin-1β Dependent Mechanisms in Human Diabetes Remission After Metabolic Surgery

To compare endocrine, metabolic, and inflammatory changes induced by gastric bypass (GB) and sleeve gastrectomy (SG) in patients with type 2 diabetes mellitus (T2DM), and to investigate the mechanisms of success after metabolic surgery. Sixteen GB and 16 SG patients were followed up before and at 1 year after surgery. The 75-g oral glucose tolerance test (OGTT) was performed before and after surgery. Glucose homeostasis, serum interleukin-1β, plasma gut hormones and adipokines, and the United Kingdom Prospective Diabetes Study (UKPDS) ten-year cardiovascular risks were evaluated. The diabetes remission rate was significantly higher in GB than SG. Changes in the area under the curve (AUC) for glucose were greater in those with complete and partial remission after GB and remitters after SG than non-remitters after SG, whereas changes in AUC for C-peptide were higher in complete and partial remitters after GB than non-remitters after SG. Insulinogenic index was enhanced and serum interleukin-1β was reduced in complete remitters after GB and remitters after SG. Logistic regression analysis confirmed that insulinogenic index and interleukin-1β, not insulin resistance, were the factors determining the success of diabetes remission after metabolic surgeries. GB and SG significantly reduced the ten-year risk of coronary heart disease and fatal coronary heart disease in T2DM patients after surgery, while GB had the additional benefit of reduced stroke risk. Human diabetes remission after metabolic surgery is through insulin secretion and interleukin-1β dependent mechanisms. GB is superior to SG in cardiocerebral risk reduction in Asian non-morbidly obese, not well-controlled T2DM patients.