Metabolites and diabetes remission after weight loss.

There is marked heterogeneity in the response to weight loss interventions with regards to weight loss amount and metabolic improvement. We sought to identify biomarkers predictive of type 2 diabetes remission and amount of weight loss in individuals with severe obesity enrolled in the Longitudinal Assessment of Bariatric Surgery (LABS) and the Look AHEAD (Action for Health in Diabetes) studies. Targeted mass spectrometry-based profiling of 135 metabolites was performed in pre-intervention blood samples using a nested design for diabetes remission over five years (n = 93 LABS, n = 80 Look AHEAD; n = 87 remitters), and for extremes of weight loss at five years (n = 151 LABS; n = 75 with high weight loss). Principal components analysis (PCA) was used for dimensionality reduction, with PCA-derived metabolite factors tested for association with both diabetes remission and weight loss. Metabolic markers were tested for incremental improvement to clinical models, including the DiaRem score. Two metabolite factors were associated with diabetes remission: one primarily composed of branched chain amino acids (BCAA) and tyrosine (odds ratio (95% confidence interval) [OR (95% CI)] = 1.4 [1.0-1.9], p = 0.045), and one with betaine and choline (OR [95% CI] = 0.7 [0.5-0.9], p = 0.02).These results were not significant after adjustment for multiple tests. Inclusion of these two factors in clinical models yielded modest improvements in model fit and performance: in a constructed clinical model, the C-statistic improved from 0.87 to 0.90 (p = 0.02), while the net reclassification index showed improvement in prediction compared to the DiaRem score (NRI = 0.26, p = 0.0013). No metabolite factors associated with weight loss at five years. Baseline levels of metabolites in the BCAA and trimethylamine-N-oxide (TMAO)-microbiome-related pathways are independently and incrementally associated with sustained diabetes remission after weight loss interventions in individuals with severe obesity. These metabolites could serve as clinically useful biomarkers to identify individuals who will benefit the most from weight loss interventions.

Intensive Weight Loss Intervention and Cancer Risk in Adults with Type 2 Diabetes: Analysis of the Look AHEAD Randomized Clinical Trial.

OBJECTIVE: This study was designed to determine whether intensive lifestyle intervention (ILI) aimed at weight loss lowers cancer incidence and mortality. METHODS: Data from the Look AHEAD trial were examined to investigate whether participants randomized to ILI designed for weight loss would have reduced overall cancer incidence, obesity-related cancer incidence, and cancer mortality, as compared with the diabetes support and education (DSE) comparison group. This analysis included 4,859 participants without a cancer diagnosis at baseline except for nonmelanoma skin cancer. RESULTS: After a median follow-up of 11 years, 684 participants (332 in ILI and 352 in DSE) were diagnosed with cancer. The incidence rates of obesity-related cancers were 6.1 and 7.3 per 1,000 person-years in ILI and DSE, respectively, with a hazard ratio (HR) of 0.84 (95% CI: 0.68-1.04). There was no significant difference between the two groups in total cancer incidence (HR, 0.93; 95% CI: 0.80-1.08), incidence of nonobesity-related cancers (HR, 1.02; 95% CI: 0.83-1.27), or total cancer mortality (HR, 0.92; 95% CI: 0.68-1.25). CONCLUSIONS: An ILI aimed at weight loss lowered incidence of obesity-related cancers by 16% in adults with overweight or obesity and type 2 diabetes. The study sample size likely lacked power to determine effect sizes of this magnitude and smaller.

Effect of preoperative body mass index on weight loss after obesity surgery.

BACKGROUND: Previous studies suggest that individuals with body mass index (BMI) above versus below 60 kg/m(2) attain lower percentage of excess weight loss (%EWL) after bariatric surgery. The objectives of this study were to (1) test whether conclusions drawn about the effect of preoperative BMI on postoperative weight loss depend on the outcome measure, (2) test for evidence of a threshold effect at BMI = 60 kg/m(2), and (3) test the effect from surgery to 12-month follow-up, relative to 12- to 36-month follow-up. METHODS: Retrospective analyses of participants grouped according to preoperative BMI: 35-39.9 (n = 232); 40-49.9 (n = 1166); 50-59.9 (n = 429);≥60 (n = 166). RESULTS: As anticipated, individuals with higher versus lower preoperative BMI had greater total weight loss but lower %EWL at all postoperative time points (all, P<.0005). However, these individuals also had lower percentage of initial weight loss (%IWL) at all time points beyond 1 month postsurgery (all, P<.0005). From 12- to 36-months, individuals with BMI 35-39.9 had 3.2±14.3 %IWL (P<.0001); 40-49.9 had 1.0±8.9 %IWL (P<.0005); 50-59.9 had-2.4±10.0 %IWL (P<.0005); and≥60 had-3.6±11.5 %IWL (P<.0005). Overall F3,1989 = 20.2, P< .0005. CONCLUSIONS: Conclusions drawn about the effect of preoperative BMI may depend on the outcome measure. A dosage effect of preoperative BMI was apparent, with heavier individuals showing lower percentages of initial and excess weight loss, regardless of BMI above or below 60 kg/m(2). Finally, this effect was particularly apparent after the initial 12-month rapid weight loss phase, when less obese (BMI<50) individuals continued losing weight, while heavier individuals (BMI≥50) regained significant weight.

Pre-bariatric surgery weight loss requirements and the effect of preoperative weight loss on postoperative outcome.

Pre-bariatric surgery requirements vary between surgeons and surgical centers, with standards of practice not yet established. The goal of this systematic review was to summarize and evaluate the available literature on pre-bariatric surgery weight loss requirements and the relation between preoperative weight loss and postoperative outcome. Major databases, including Medline, PubMed and PsychINFO were searched for relevant articles. Case studies, studies>20 years old and studies that utilized self-reported body weight data were excluded. Data on the effect of the following was summarized: (1) preoperative requirements on preoperative weight loss; (2) insurance-mandated preoperative requirements; (3) the contingency of receipt of surgery; (4) preoperative weight loss on postoperative weight loss and (5) preoperative weight loss on perioperative and postoperative complication and comorbidity rates. The majority of studies suggest that: (1) current preoperative requirements held by the majority of third party payer organizations in the United States are ineffective in fostering preoperative weight loss; (2) making receipt of surgery contingent upon achieving preoperative weight loss, and meal-replacement diets, may be particularly effective in fostering preoperative weight loss and (3) preoperative weight loss may lead to improvements in at least some relevant postoperative outcomes. However, a preoperative weight loss mandate may lead to the denial of surgery and subsequent health benefits to individuals who are unable to achieve a prespecified amount of weight. Overall, the limited number and quality of prospective studies in this area prohibits the much-needed establishment of standards of practice for pre-bariatric requirements.