National Differences in Remission of Type 2 Diabetes Mellitus After Roux-en-Y Gastric Bypass Surgery-Subgroup Analysis of 2-Year Results of the Diabetes Surgery Study Comparing Taiwanese with Americans with Mild Obesity (BMI 30-35 kg/m2).

BACKGROUND: The purpose of this study is to compare effects of different nations on Roux-en-Y gastric bypass (RYGB) vs. intensive medical management (IMM) in achieving remission of type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Between April 2008 and December 2011, this randomized, controlled clinical trial was conducted at four teaching hospitals in the United States and Taiwan involving 71 participants with mild obesity (BMI 30-35 kg/m2). Thirty-six of 71 participants were randomly assigned to the RYGB group, and the others were in IMM group. Partial or complete remission of T2DM was defined as blood HbA1c < 6.5 % (48 mmol/mol) or <6 % (42 mmol/mol) without any antihyperglycemic medication for at least 1-year duration, respectively. RESULTS: At baseline, Taiwanese participants had a lower BMI, younger age, and shorter duration of T2DM than American participants. At 24 months, weight loss was greater in the RYGB group in both populations than in the IMM group. No IMM participant of either population had partial or complete remission of T2DM. In the RYGB group, a substantial proportion of the subjects achieved complete or partial remission (57 % in Taiwanese and 27 % in American participants, P = 0.08). Logistic regression revealed stimulated C-peptide (Odds ratio 2.22, P = 0.02) but not nationality as a significant predictor of diabetes remission. CONCLUSION: Adding RYGB to lifestyle and medical management was associated with a greater likelihood of remission of T2DM in both Taiwanese and American subjects with mild obesity with type 2 diabetes. Residual beta-cell function at baseline appears to be the major factor predicting remission of T2DM. Trial registry number: clinicaltrials.gov Identifier: NCT00641251.

Roux-en-Y gastric bypass for diabetes (the Diabetes Surgery Study): 2-year outcomes of a 5-year, randomised, controlled trial.

BACKGROUND: Conventional treatments for patients with type 2 diabetes are often inadequate. We aimed to assess outcomes of diabetes control and treatment risks 2 years after adding Roux-en-Y gastric bypass to intensive lifestyle and medical management. METHODS: We report 2-year outcomes of a 5-year randomised trial (the Diabetes Surgery Study) at four teaching hospitals (three in the USA and one in Taiwan). At baseline, eligible participants had to have HbA1c of at least 8·0% (64 mmol/mol), BMI between 30·0 and 39·9 kg/m(2), and type 2 diabetes for at least 6 months, and be aged 30-67 years. We randomly assigned participants to receive either intensive lifestyle and medical management alone (lifestyle and medical management), or lifestyle and medical management plus standard Roux-en-Y gastric bypass surgery (gastric bypass). Staff from the clinical centres had access to data from individual patients, but were masked to other patients' data and aggregated data until the 2-year follow-up. Drugs for hyperglycaemia, hypertension, and dyslipidaemia were prescribed by protocol. The primary endpoint was achievement of the composite treatment goal of HbA1c less than 7·0% (53 mmol/mol), LDL cholesterol less than 2·59 mmol/L, and systolic blood pressure less than 130 mm Hg at 12 months; here we report the composite outcome and other pre-planned secondary outcomes at 24 months. Analyses were done on an intention-to-treat basis, with multiple imputations for missing data. This study is registered with ClinicalTrials.gov, number NCT00641251, and is still ongoing. FINDINGS: Between April 21, 2008, and Nov 21, 2011, we randomly assigned 120 eligible patients to either lifestyle and medical management alone (n=60) or with the addition of gastric bypass (n=60). One patient in the lifestyle and medical management group died (from pancreatic cancer), thus 119 were included in the primary analysis. Significantly more participants in the gastric bypass group achieved the composite triple endpoint at 24 months than in the lifestyle and medical management group (26 [43%] vs eight [14%]; odds ratio 5·1 [95% CI 2·0-12·6], p=0·0004), mainly through improved glycaemic control (HbA1c <7·0% [53 mmol/mol] in 45 [75%] vs 14 [24%]; treatment difference -1·9% (-2·5 to -1·4); p=0·0001). 46 clinically important adverse events occurred in the gastric bypass group and 25 in the lifestyle and medical management group (mainly infections in both groups [four in the lifestyle and medical management group, eight in the gastric bypass group]). With a negative binomial model adjusted for site, the event rate for the gastric bypass group was non-significantly higher than the lifestyle and medical management group by a factor of 1·67 (95% CI 0·98-2·87, p=0·06). Across both years of the study, the gastric bypass group had seven serious falls with five fractures, compared with three serious falls and one fracture in the lifestyle and medical management group. All fractures happened in women. Many more nutritional deficiencies occurred in the gastric bypass group (mainly deficiencies in iron, albumin, calcium, and vitamin D), despite protocol use of nutritional supplements. INTERPRETATION: The addition of gastric bypass to lifestyle and medical management in patients with type 2 diabetes improved diabetes control, but adverse events and nutritional deficiencies were more frequent. Larger and longer studies are needed to investigate whether the benefits and risk of gastric bypass for type 2 diabetes can be balanced. FUNDING: Covidien, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Nutrition Obesity Research Centers, and the National Center for Advancing Translational Sciences.

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.

Measuring perceived barriers to healthful eating in obese, treatment-seeking adults.

OBJECTIVE: To characterize perceived barriers to healthful eating in a sample of obese, treatment-seeking adults and to examine whether changes in barriers are associated with energy intake and body weight. DESIGN: Observational study based on findings from a randomized, controlled behavioral weight-loss trial. PARTICIPANTS: Participants were 113 women and 100 men, mean age 48.8 years, 67% white, and mean body mass index at baseline 34.9 kg/m(2). VARIABLES MEASURED: Perceived diet barriers were assessed using a 39-item questionnaire. Energy intake was assessed with the Block Food Frequency Questionnaire. Body weight (kg) and height (cm) were measured. ANALYSIS: Factor-based scales constructed from exploratory factor analysis. Linear regression models regressed 12-month energy intake and body weight on baseline to 12-month factor-based score changes (α = .05). RESULTS: Exploratory factor analysis yielded 3 factors: lack of knowledge, lack of control, and lack of time. Reported declines in lack of knowledge and lack of control from baseline to 12 months were associated with significantly greater energy restriction over 12 months, whereas reported declines in lack of control and lack of time were associated with significantly greater weight loss. CONCLUSIONS AND IMPLICATIONS: Results suggest that declines in perceived barriers to healthful eating during treatment are associated with greater energy restriction and weight loss.

Sex-specific HDL cholesterol changes with weight loss and their association with anthropometric variables: the LIFE study.

Decrease in the level of high-density lipoprotein cholesterol (HDLC) has been observed in women who start dieting, but not in men. Patterns of HDLC change during intentional weight loss through 30-months of follow-up, and their association with changes in anthropometric measurements were examined in obese women (N = 112) and men (N = 100). Missing HDLC values at 6-, 12-, 18-, and 30-month follow-up (N = 16, 34, 55, and 50, respectively) due to dropout were imputed by multiple imputation. Mean ages and BMIs of subjects at baseline were 47.2 years and 34.8 kg/m(2) for women, and 50.4 years and 35.0 kg/m(2) for men. On average, participants lost weight steadily for 12 months, followed by slow regain. During the first 6 months, HDLC decreased significantly in women (-4.1 mg/dl, P = 0.0007), but not in men. Significant HDLC increases were observed in both men and women from 6- to 12-month follow-up. HDLC changes in women were positively associated with changes in hip circumference from baseline to 12-month independent of changes in triglycerides (TG), glucose, and insulin. Rapid decrease of predominantly subcutaneous fat in the femoral and gluteal area might be associated with HDLC decrease in women during initial weight loss.

Maintenance-tailored therapy vs. standard behavior therapy for 30-month maintenance of weight loss.

OBJECTIVE: To assess differences in weight regain one year after an 18-month obesity treatment with standard behavior therapy (SBT) or maintenance-tailored therapy for obesity (MTT). METHOD: 213 obese adult volunteers were treated for 18 months using SBT with fixed behavioral prescriptions or MTT that employed varied behavioral prescriptions with treatment breaks. Follow-up analysis focused on weight maintenance after a year of no contact. The trial was conducted at the University of Minnesota between 2005 and 2009. RESULTS: Mean (SD) weight change between 18 and 30 months for participants in the SBT group was +4.1 kg (4.4) compared to +2.8 kg (4.5) in the MTT group. This is a 31% reduction in weight regain in MTT relative to SBT (p=0.078). This trend toward better maintenance in MTT versus SBT was due primarily to superior differential maintenance in MTT participants in the highest tertile of total weight loss at 18 months, i.e. MTT participants in this tertile regained 4 kg less than SBT participants between 18 and 30 months. CONCLUSIONS: The MTT approach with varied content and timing produced more desirable patterns of weight loss maintenance than the traditional SBT approach, especially among individuals who had achieved greater initial weight loss.

Energy density and weight change in a long-term weight-loss trial.

BACKGROUND: Health risks linked to obesity and the difficulty most have in achieving weight loss underscore the importance of identifying dietary factors that contribute to successful weight loss. METHODS: This study examined the association between change in dietary energy density and weight loss over time. Subjects were 213 men and women with BMI of 30-39 kg/m2 and without chronic illness enrolled in 2004 in a randomized trial evaluating behavioral treatments for long-term weight loss. Subjects completed a 62-item food frequency questionnaire at baseline and at 6, 12, and 18 months. RESULTS: Pearson correlations between BMI and energy density (kcals/g of solid food) at baseline were not significantly different from zero (r = -0.02, p = 0.84). In a longitudinal analysis, change in energy density was strongly related to change in BMI. The estimated beta for change in BMI (kg/m2) of those in the quartile representing greatest decrease in energy density at 18 months compared to those in the quartile with the least was -1.95 (p = 0.006). The association was especially strong in the first six months (estimated beta = -1.43), the period with greatest weight loss (mean change in BMI = -2.50 kg/m2 from 0-6 months vs. 0.23 kg/m2 from 12-18 months) and the greatest contrast with respect to change in energy density. CONCLUSION: Decreased energy density predicted weight loss in this 18 month weight loss study. These findings may have important implications for individual dietary advice and public health policies targeting weight control in the general population.

A comparison of maintenance-tailored therapy (MTT) and standard behavior therapy (SBT) for the treatment of obesity.

OBJECTIVE: To evaluate a maintenance-tailored therapy (MTT) compared to standard behavior therapy (SBT) for treatment of obesity. MAIN OUTCOME MEASURE: change in body weight. METHOD: A non-blinded, randomized trial comparing effectiveness of MTT and SBT in facilitating sustained weight loss over 18 months; 213 adult volunteers> or =18 years participated. SBT had fixed behavioral goals, MTT goals varied over time. Study conducted at the University of Minnesota, School of Public Health, January 2005 through September 2007. RESULTS: Mean (SD) weight losses at 6, 12, and 18 months were 5.7 (5.0) kg, 8.2 (8.6) kg and 8.3 (8.9) kg for MTT and 7.4 (3.9) kg, 10.7 (8.2) kg and 9.3 (8.8) kg for SBT. Total weight loss did not differ by group at 18 months, but the time pattern differed significantly (p<0.001). The SBT group lost more weight in the first 6 months. Both groups lost similar amounts between 6 and 12 months; MTT had stable weight between 12 and 18 months, while SBT experienced significant weight gain. CONCLUSIONS: The MTT approach produced sustained weight loss for an unusually long period of time and not achieved in previous trials of behavioral treatment for weight loss. The MTT approach, therefore, deserves further study.

Mood, Weight, and Physical Activity Among Obese Individuals Enrolled In a Long-term Weight-loss Program: Trajectories and Associations with Gender.

OBJECTIVE: To examine the trajectories of mood, weight and physical activity, and associations between mood, weight, and gender, among 213 obese individuals. METHODS: Prospective, longitudinal design. Assessments at baseline and 6, 12, and 18 months of Profile of Mood States, Paffenbarger Physical Activity Questionnaire, and weight. RESULTS: Total mood disturbance decreased from baseline to 6 months, with no change thereafter. Weight decreased from baseline to 6 to 12 months, and increased from 12 to 18 months. Physical activity increased from baseline to 6 months, and 12 to 18 months. Increased physical activity predicted greater vigor and less fatigue over time. Females high in distress at 6 months lost less weight than females low in distress and at 18 months gained more weight than those low in distress. There were no such associations among males. CONCLUSION: The trajectories of mood, weight and physical activity were synchronous only in the short-term. Distress monitoring, targeted to females who relapse, may be warranted.