Browsing by Author "Bray, George A."

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    Depression as a Predictor of Weight Regain Among Successful Weight Losers in the Diabetes Prevention Program
    (2013-02) Price, David W.; Ma, Yong; Rubin, Richard R.; Perreault, Leigh; Bray, George A.; Marrero, David G.; Knowler, William C.; Barrett-Connor, Elizabeth; LaCoursiere, D. Yvette
    OBJECTIVE: To determine whether depression symptoms or antidepressant medication use predicts weight regain in overweight individuals with impaired glucose tolerance (IGT) who are successful with initial weight loss. RESEARCH DESIGN AND METHODS: A total of 1,442 participants who successfully lost at least 3% of their baseline body weight after 12 months of participation in the randomized controlled Diabetes Prevention Program (DPP) continued in their assigned treatment group (metformin, intensive lifestyle, or placebo) and were followed into the Diabetes Prevention Program Outcome Study (DPPOS). Weight regain was defined as a return to baseline DPP body weight. Participant weight and antidepressant medication use were assessed every 6 months. Depression symptoms (Beck Depression Inventory [BDI] score ≥11) were assessed every 12 months. RESULTS: Only 2.7% of the overall cohort had moderate to severe depression symptoms at baseline; most of the participants with BDI score ≥11 had only mild symptoms during the period of observation. In unadjusted analyses, both depression symptoms (hazard ratio 1.31 [95% CI 1.03-1.67], P = 0.03) and antidepressant medication use at either the previous visit (1.72 [1.37-2.15], P < 0.0001) or cumulatively as percent of visits (1.005 [1.002-1.008], P = 0.0003) were predictors of subsequent weight regain. After adjustment for multiple covariates, antidepressant use remained a significant predictor of weight regain (P < 0.0001 for the previous study visit; P = 0.0005 for the cumulative measure), while depression symptoms did not. CONCLUSIONS: In individuals with IGT who do not have severe depression and who initially lose weight, antidepressant use may increase the risk of weight regain.
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    Non-traditional biomarkers and incident diabetes in the Diabetes Prevention Program: comparative effects of lifestyle and metformin interventions
    (Springer Verlag, 2018-10-17) Goldberg, Ronald B.; Bray, George A.; Marcovina, Santica M.; Mather, Kieren J.; Orchard, Trevor J.; Perreault, Leigh; Temprosa, Marinella; Medicine, School of Medicine
    We compared the associations of circulating biomarkers of inflammation, endothelial and adipocyte dysfunction and coagulation with incident diabetes in the placebo, lifestyle and metformin intervention arms of the Diabetes Prevention Program, a randomised clinical trial, to determine whether reported associations in general populations are reproduced in individuals with impaired glucose tolerance, and whether these associations are independent of traditional diabetes risk factors. We further investigated whether biomarker-incident diabetes associations are influenced by interventions that alter pathophysiology, biomarker concentrations and rates of incident diabetes. METHODS: The Diabetes Prevention Program randomised 3234 individuals with impaired glucose tolerance into placebo, metformin (850 mg twice daily) and intensive lifestyle groups and showed that metformin and lifestyle reduced incident diabetes by 31% and 58%, respectively compared with placebo over an average follow-up period of 3.2 years. For this study, we measured adiponectin, leptin, tissue plasminogen activator (as a surrogate for plasminogen activator inhibitor 1), high-sensitivity C-reactive protein, IL-6, monocyte chemotactic protein 1, fibrinogen, E-selectin and intercellular adhesion molecule 1 at baseline and at 1 year by specific immunoassays. Traditional diabetes risk factors were defined as family history, HDL-cholesterol, triacylglycerol, BMI, fasting and 2 h glucose, HbA1c, systolic blood pressure, inverse of fasting insulin and insulinogenic index. Cox proportional hazard models were used to assess the effects of each biomarker on the development of diabetes assessed semi-annually and the effects of covariates on these. RESULTS: E-selectin, (HR 1.19 [95% CI 1.06, 1.34]), adiponectin (0.84 [0.71, 0.99]) and tissue plasminogen activator (1.13 [1.03, 1.24]) were associated with incident diabetes in the placebo group, independent of diabetes risk factors. Only the association between adiponectin and diabetes was maintained in the lifestyle (0.69 [0.52, 0.92]) and metformin groups (0.79 [0.66, 0.94]). E-selectin was not related to diabetes development in either lifestyle or metformin groups. A novel association appeared for change in IL-6 in the metformin group (1.09 [1.021, 1.173]) and for baseline leptin in the lifestyle groups (1.31 [1.06, 1.63]). CONCLUSIONS/INTERPRETATION: These findings clarify associations between an extensive group of biomarkers and incident diabetes in a multi-ethnic cohort with impaired glucose tolerance, the effects of diabetes risk factors on these, and demonstrate differential modification of associations by interventions. They strengthen evidence linking adiponectin to diabetes development, and argue against a central role for endothelial dysfunction. The findings have implications for the pathophysiology of diabetes development and its prevention.
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    The prevention of type 2 diabetes
    (2008-07) Crandall, Jill P.; Knowler, William C.; Kahn, Steven E.; Marrero, David G.; Florez, Jose C.; Bray, George A.; Haffner, Steven M.; Hoskin, Mary; Nathan, David M.; Diabetes Prevention Program Research Group
    Type 2 diabetes mellitus (T2DM) affects more than 7% of adults in the US and leads to substantial personal and economic burden. In prediabetic states insulin secretion and action—potential targets of preventive interventions—are impaired. In trials lifestyle modification (i.e. weight loss and exercise) has proven effective in preventing incident T2DM in high-risk groups, although weight loss has the greatest effect. Various medications (e.g. metformin, thiazolidinediones and acarbose) can also prevent or delay T2DM. Whether diabetes-prevention strategies also ultimately prevent the development of diabetic vascular complications is unknown, but cardiovascular risk factors are favorably affected. Preventive strategies that can be implemented in routine clinical settings have been developed and evaluated. Widespread application has, however, been limited by local financial considerations, even though cost-effectiveness might be achieved at the population level.