761 research outputs found

    Insulin-associated weight gain in obese type 2 diabetes mellitus patients: What can be done?

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    Insulin therapy (IT ) is initiated for patients with type 2 diabetes mellitus when glycaemic targets are not met with diet and other hypoglycaemic agents. The initiation of IT improves glycaemic control and reduces the risk of microvascular complications. There is, however, an associated weight gain following IT , which may adversely affect diabetic and cardiovascular morbidity and mortality. A 3 to 9 kg insulin‐associated weight gain (IAWG ) is reported to occur in the first year of initiating IT , predominantly caused by adipose tissue. The potential causes for this weight gain include an increase in energy intake linked to a fear of hypoglycaemia, a reduction in glycosuria, catch‐up weight, and central effects on weight and appetite regulation. Patients with type 2 diabetes who are receiving IT often have multiple co‐morbidities, including obesity, that are exacerbated by weight gain, making the management of their diabetes and obesity challenging. There are several treatment strategies for patients with type 2 diabetes, who require IT , that attenuate weight gain, help improve glycaemic control, and help promote body weight homeostasis. This review addresses the effects of insulin initiation and intensification on IAWG , and explores its potential underlying mechanisms, the predictors for this weight gain, and the available treatment options for managing and limiting weight gain

    A randomized controlled trial: the effect of inulin on weight management and ectopic fat in subjects with prediabetes.

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    BACKGROUND: Fat infiltration of the liver, muscle and pancreas is associated with insulin resistance and risk of diabetes. Weight loss reduces ectopic fat deposition and risk of diabetes, but is difficult to sustain to due to compensatory increases in appetite. Fermentable carbohydrates have been shown to decrease appetite and food intake, and promote weight loss in overweight subjects. In animal studies, fermentable carbohydrate reduces ectopic fat independent of weight loss. We aimed to investigate the effect of the fermentable carbohydrate inulin on weight maintenance, appetite and ectopic fat in subjects with prediabetes. METHODS: Forty-four subjects with prediabetes were randomized to 18 weeks' inulin or cellulose supplementation. During weeks 1-9 (weight loss phase) all subjects had four visits with a dietitian to guide them towards a 5 % weight loss. During weeks 10-18 (weight maintenance phase) subjects continued taking their assigned supplementation and were asked to maintain the weight they had lost but were offered no further support. All subjects attended study sessions at baseline, 9 and 18 weeks for measurement of weight; assessment of adipose tissue and ectopic fat content by magnetic resonance imaging and magnetic resonance spectroscopy; glucose, insulin and GLP-1 levels following a meal tolerance test; and appetite by ad libitum meal test and visual analogue scales. RESULTS: Both groups lost approximately 5 % of their body weight by week nine (-5.3 ± 0.1 % vs -4.3 ± 0.4 %, p = 0.13, but the inulin group lost significantly more weight between 9 and 18 weeks (-2.3 ± 0.5 % vs -0.6 ± 0.4 %, p = 0.012). Subjects taking inulin had lower hepatic (p = 0.02) and soleus muscle (p < 0.05) fat content at 18 weeks compared to control even after controlling for weight loss and consumed less at the ad libitum meal test (p = 0.027). Fasting glucose significantly decreased at week nine only (p = 0.005), insulin concentrations did not change, and there was a significant increase in GLP-1 in the cellulose group at 9 and 18 weeks (p < 0.03, p < 0.00001). CONCLUSION: Inulin may have a two-pronged effect on the risk of diabetes by 1) promoting weight loss 2) reducing intrahepatocellular and intramyocellular lipid in people with prediabetes independent of weight loss

    Interpreting and Reporting Results Based on Patient-Reported Outcomes

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    AbstractThis article deals with the incorporation of patient-reported outcomes (PROs) into clinical trials and focuses on issues associated with the interpretation and reporting of PRO data. The primary focus and context of this information relates to the evidentiary support and reporting for a labeling or advertising claim of a PRO benefit for a new or approved pharmaceutical product. This manuscript focuses on issues associated with assessing clinical significance and common pitfalls to avoid in presenting results related to PROs. Specifically, the questions addressed by this manuscript involve: What are the best methods to assess clinical significance for PROs? How should investigators present PRO data most effectively in a Food and Drug Administration (FDA) application? In labeling or in a scientific publication? Guidelinesfor interpreting clinical significance of PROs and for comprehensively reporting on the methods, measures and results of clinical trials that incorporate PROs are important for clinicians, regulatory agencies, and most of all to patients. Clear specifications for considering a finding on a PRO measure, as clinically meaningful, need to be determined by instrument developers and psychometricians; they need to be reported for all clinical trials involving PRO end points. Clinical trial reports need to be comprehensive, clear, and sufficient to enable any reader to understand the methods, PRO measures, statistical analysis, and results

    C\u3csub\u3e60\u3c/sub\u3e and Sc\u3csub\u3e3\u3c/sub\u3eN@C\u3csub\u3e80\u3c/sub\u3e(TMB-PPO) Derivatives as Constituents of Singlet Oxygen Generating, Thiol-ene Polymer Nanocomposites

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    Numerous functionalization methods have been employed to increase the solubility, and therefore, the processability of fullerenes in composite structures, and of these radical addition reactions continue to be an important methodology. C60 and Sc3N@C80 derivatives were prepared via radical addition of the photodecomposition products from the commercial photoinitiator TMB-PPO, yielding C60(TMB-PPO)5 and Sc3N@C80(TMB-PPO)3 as preferred soluble derivatives obtained in high yields. Characterization of the mixture of isomers using standard techniques suggests an overall 1PPO:6TMB ratio of addends, reflecting the increased reactivity of the carbon radical. Although, a higher percentage of PPO is observed in the Sc3N@C80(TMB-PPO)3 population, perhaps due to reverse electronic requirements of the substrate. Visually dispersed thiol-ene nanocomposites with low extractables were prepared using two monomer compositions (PETMP:TTT and TMPMP:TMPDE) with increasing fullerene derivative loading to probe network structure-property relationships. Thermal stability of the derivatives and the resulting networks decreased with increased functionality and at high fullerene loadings, respectively. TMPMP:TMPDE composite networks show well-dispersed derivatives via TEM imaging, and increasing Tg’s with fullerene loading, as expected for the incorporation of a more rigid network component. PETMP:TTT composites show phase separation in TEM, which is supported by the observed Tg’s. Singlet oxygen generation of the derivatives decreases with increased functionality; however, this is compensated for by the tremendous increase in solubility in organic solvents and miscibility with monomers. Most importantly, singlet oxygen generation from the composites increased with fullerene derivative loading, with good photostability of the networks

    Analysis and Interpretation of Results Based on Patient-Reported Outcomes

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    AbstractThis article is part of a series of manuscripts dealing with the incorporation of patient-reported outcomes (PROs) into clinical trials. The issues dealt with in this manuscript concern the common pitfalls to avoid in statistical analysis and interpretation of PROs. Specifically, the questions addressed by this manuscript involve the analysis pitfalls with PRO data in clinical trials and how can they be avoided (e.g.,missing data, multiplicity, null results etc.). The manuscript provides key literature for existing resources and proposes new guidelines

    Commentary on the Integration of Model Sharing and Reproducibility Analysis to Scholarly Publishing Workflow in Computational Biomechanics

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    © 1964-2012 IEEE.Objective: The overall goal of this paper is to demonstrate that dissemination of models and analyses for assessing the reproducibility of simulation results can be incorporated in the scientific review process in biomechanics. Methods: As part of a special issue on model sharing and reproducibility in the IEEE Transactions on Biomedical Engineering, two manuscripts on computational biomechanics were submitted: Rajagopal et al., IEEE Trans. Biomed. Eng., 2016 and Schmitz and Piovesan, IEEE Trans. Biomed. Eng., 2016. Models used in these studies were shared with the scientific reviewers and the public. In addition to the standard review of the manuscripts, the reviewers downloaded the models and performed simulations that reproduced results reported in the studies. Results: There was general agreement between simulation results of the authors and those of the reviewers. Discrepancies were resolved during the necessary revisions. The manuscripts and instructions for download and simulation were updated in response to the reviewers' feedback; changes that may otherwise have been missed if explicit model sharing and simulation reproducibility analysis was not conducted in the review process. Increased burden on the authors and the reviewers, to facilitate model sharing and to repeat simulations, were noted. Conclusion: When the authors of computational biomechanics studies provide access to models and data, the scientific reviewers can download and thoroughly explore the model, perform simulations, and evaluate simulation reproducibility beyond the traditional manuscript-only review process. Significance: Model sharing and reproducibility analysis in scholarly publishing will result in a more rigorous review process, which will enhance the quality of modeling and simulation studies and inform future users of computational models

    Nuclear matrix element for two neutrino double beta decay from 136Xe

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    The nuclear matrix element for the two neutrino double beta decay (DBD) of 136Xe was evaluated by FSQP (Fermi Surface Quasi Particle model), where experimental GT strengths measured by the charge exchange reaction and those by the beta decay rates were used. The 2 neutrino DBD matrix element is given by the sum of products of the single beta matrix elements via low-lying (Fermi Surface) quasi-particle states in the intermediate nucleus. 136Xe is the semi-magic nucleus with the closed neutron-shell, and the beta + transitions are almost blocked. Thus the 2 neutrino DBD is much suppressed. The evaluated 2 neutrino DBD matrix element is consistent with the observed value.Comment: 7 pages 6 figure
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