Glycemic control is improved more after gastric bypass surgery (GBP) than after equivalent diet-induced weight loss in patients with morbid obesity and type 2 diabetes mellitus. We applied metabolomic profiling to understand the mechanisms of this better metabolic response after GBP. Circulating amino acids (AAs) and acylcarnitines (ACs) were measured in plasma from fasted subjects by targeted tandem mass spectrometry before and after a matched 10-kilogram weight loss induced by GBP or diet. Total AAs and branched-chain AAs (BCAAs) decreased after GBP, but not after dietary intervention. Metabolites derived from BCAA oxidation also decreased only after GBP. Principal components (PC) analysis identified two major PCs, one composed almost exclusively of ACs (PC1) and another with BCAAs and their metabolites as major contributors (PC2). PC1 and PC2 were inversely correlated with pro-insulin concentrations, the C-peptide response to oral glucose, and the insulin sensitivity index after weight loss, whereas PC2 was uniquely correlated with levels of insulin resistance (HOMA-IR). These data suggest that the enhanced decrease in circulating AAs after GBP occurs by mechanisms other than weight loss and may contribute to the better improvement in glucose homeostasis observed with the surgical intervention.

Aims/hypothesis Insulin resistance (IR) improves with weight loss, but this response is heterogeneous. We hypothesised that metabolomic profiling would identify biomarkers predicting changes in IR with weight loss. Methods Targeted mass spectrometry-based profiling of 60 metabolites, plus biochemical assays of NEFA, β-hydroxybutyrate, ketones, insulin and glucose were performed in baseline and 6 month plasma samples from 500 participants who had lost ≥4 kg during Phase I of the Weight Loss Maintenance (WLM) trial. Homeostatic model assessment of insulin resistance (HOMA-IR) and change in HOMA-IR with weight loss (ΔHOMA-IR) were calculated. Principal components analysis (PCA) and mixed models adjusted for race, sex, baseline weight, and amount of weight loss were used; findings were validated in an independent cohort of patients (n=22). Results Mean weight loss was 8.67±4.28 kg; mean ΔHOMA-IR was −0.80±1.73, range −28.9 to 4.82). Baseline PCA-derived factor 3 (branched chain amino acids [BCAAs] and associated catabolites) correlated with baseline HOMA-IR (r=0.50, p<0.0001) and independently associated with ΔHOMA-IR (p<0.0001). ΔHOMA-IR increased in a linear fashion with increasing baseline factor 3 quartiles. Amount of weight loss was only modestly correlated with ΔHOMA-IR (r=0.24). These findings were validated in the independent cohort, with a factor composed of BCAAs and related metabolites predicting ΔHOMA-IR (p=0.007). Conclusions/interpretation A cluster of metabolites comprising BCAAs and related analytes predicts improvement in HOMA-IR independent of the amount of weight lost. These results may help identify individuals most likely to benefit from moderate weight loss and elucidate novel mechanisms of IR in obesity.

Return to the disabled list after Tommy John surgery is common among professional pitchers (>50%), and performance declines across several major metrics after surgery. Patients undergoing Tommy John surgery should be counseled appropriately regarding the likelihood of return to preinjury levels of competition and performance.

OBJECTIVES This study assessed the effectiveness of a previously tested model, Critical Time Intervention (CTI), in producing an enduring reduction in homelessness for persons with severe mental illness who were discharged from inpatient psychiatric treatment facilities. METHODS A total of 150 previously homeless men and women who were diagnosed with severe mental illness and were discharged from inpatient psychiatric hospitalization were randomly assigned to receive either usual care or usual care plus CTI. The nine-month CTI intervention aims to gradually pass responsibility for providing ongoing support to community sources that will remain in place after the intervention ends, thereby leading to a durable reduction in the risk of future homelessness. Participants’ housing status was assessed every six weeks for eighteen months via participant self-report collected by interviewers blind to condition. RESULTS In an intent-to-treat analysis, participants assigned to the CTI group had significantly less homelessness at the end of the follow-up period (the final three six-week intervals) than did those assigned to the control group (OR=0.22, 95% CI=.06--.88). CONCLUSIONS We have shown that a relatively brief, focused intervention for persons with severe mental illness led to a reduction in homelessness that was evident nine months after the end of the intervention. This work suggests that targeted, relatively short interventions applied at critical transition points may enhance the efficacy of long-term supports for persons with severe mental illness living in the community.

Genetic association studies can be used to identify factors that may contribute to disparities in disease evident across different racial and ethnic populations. However, such studies may not account for potential confounding if study populations are genetically heterogeneous. Racial and ethnic classifications have been used as proxies for genetic relatedness. We investigated genetic admixture and developed a questionnaire to explore variables used in constructing racial identity in two cohorts: 50 African Americans and 40 Nigerians. Genetic ancestry was determined by genotyping 107 ancestry informative markers. Ancestry estimates calculated with maximum likelihood estimation were compared with population stratification detected with principal components analysis. Ancestry was approximately 95% west African, 4% European, and 1% Native American in the Nigerian cohort and 83% west African, 15% European, and 2% Native American in the African American cohort. Therefore, self-identification as African American agreed well with inferred west African ancestry. However, the cohorts differed significantly in mean percentage west African and European ancestries (P < 0.0001) and in the variance for individual ancestry (P V 0.01). Among African Americans, no set of questionnaire items effectively estimated degree of west African ancestry, and self-report of a high degree of African ancestry in a three-generation family tree did not accurately predict degree of African ancestry. Our findings suggest that self-reported race and ancestry can predict ancestral clusters but do not reveal the extent of admixture. Genetic classifications of ancestry may provide a more objective and accurate method of defining homogenous populations for the investigation of specific population-disease associations. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1329 -38)