53,258 research outputs found

    Urinary peptidomics provides a noninvasive humanized readout of diabetic nephropathy in mice

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    Nephropathy is among the most frequent complications of diabetes and the leading cause of end-stage renal disease. Despite the success of novel drugs in animal models, the majority of the subsequent clinical trials employing those drugs targeting diabetic nephropathy failed. This lack of translational value may in part be due to an inadequate comparability of human disease and animal models that often capture only a few aspects of disease. Here we overcome this limitation by developing a multimolecular noninvasive humanized readout of diabetic nephropathy based on urinary peptidomics. The disease-modified urinary peptides of 2 type 2 diabetic nephropathy mouse models were identified and compared with previously validated urinary peptide markers of diabetic nephropathy in humans to generate a classifier composed of 21 ortholog peptides. This classifier predicted the response to disease and treatment with inhibitors of the renin-angiotensin system in mice. The humanized classifier was significantly correlated with glomerular lesions. Using a human type 2 diabetic validation cohort of 207 patients, the classifier also distinguished between patients with and without diabetic nephropathy, and their response to renin-angiotensin system inhibition. Thus, a combination of multiple molecular features common to both human and murine disease could provide a significant change in translational drug discovery research in type 2 diabetic nephropathy

    Oral diabetes medication monotherapy and short-term mortality in individuals with type 2 diabetes and coronary artery disease

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    Objective To determine whether sulfonylurea use, compared with non-sulfonylurea oral diabetes medication use, was associated with 2-year mortality in individuals with well-controlled diabetes and coronary artery disease (CAD). Research design and methods We studied 5352 US veterans with type 2 diabetes, obstructive CAD on coronary angiography, hemoglobin A1c ≤7.5% at the time of catheterization, and taking zero or one oral diabetes medication (categorized as no medications, non-sulfonylurea medication, or sulfonylurea). We estimated the association between medication category and 2-year mortality using inverse probability of treatment-weighted (IPW) standardized mortality differences and IPW multivariable Cox proportional hazards regression. Results 49%, 35%, and 16% of the participants were on no diabetes medications, non-sulfonylurea medications, and sulfonylureas, respectively. In individuals on no medications, non-sulfonylurea medications, and sulfonylureas, the unadjusted mortality rates were 6.6%, 5.2%, and 11.9%, respectively, and the IPW-standardized mortality rates were 5.9%, 6.5%, and 9.7%, respectively. The standardized absolute 2-year mortality difference between non-sulfonylurea and sulfonylurea groups was 3.2% (95% CI 0.7 to 5.7) (p=0.01). In Cox proportional hazards models, the point estimate suggested that sulfonylurea use might be associated with greater hazard of mortality than non-sulfonylurea medication use, but this finding was not statistically significant (HR 1.38 (95% CI 1.00 to 1.93), p=0.05). We did not observe significant mortality differences between individuals on no diabetes medications and non-sulfonylurea users. Conclusions Sulfonylurea use was common (nearly one-third of those taking medications) and was associated with increased 2-year mortality in individuals with obstructive CAD. The significance of the association between sulfonylurea use and mortality was attenuated in fully adjusted survival models. Caution with sulfonylurea use may be warranted for patients with well-controlled diabetes and CAD, and metformin or newer diabetes medications with cardiovascular safety data could be considered as alternatives when individualizing therapy

    The Arabs Between East and West

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    News release announcing a speech by Dr. Fawzi Abu-Diab on The Arabs Between East and West

    Developing priorities to achieve health equity through diabetes translation research: A concept mapping study

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    Introduction: The goal of diabetes translation research is to advance research into practice and ensure equitable benefit from scientific evidence. This study uses concept mapping to inform and refine future directions of diabetes translation research with the goal of achieving health equity in diabetes prevention and control. Research design and methods: This study used concept mapping and input from a national network of diabetes researchers and public health practitioners. Concept mapping is a mixed-method, participant-based process. First, participants generated statements by responding to a focus prompt ( Results: Ten clusters were identified containing between 6 and 12 statements from 95 total generated statements. The ranges of average importance and feasibility ratings for clusters were fairly high and narrow (3.62-4.09; 3.10-3.93, respectively). Clusters with the most statements in the go-zone quadrant (above average importance/feasibility) were Conclusions: This study created a framework of 10 priority areas to guide current and future efforts in diabetes translation research to achieve health equity. Themes rated as highly important and feasible provide the basis to evaluate current research support. Future efforts should explore how to best support innovative-targets, those rated highly important but less feasible

    Effective diabetes complication management is a step toward a carbon-efficient planet: an economic modeling study

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    Background The management of diabetes-related complications accounts for a large share of total carbon dioxide equivalent (CO2e) emissions. We assessed whether improving diabetes control in people with type 2 diabetes reduces CO2e emissions, compared with those with unchanging glycemic control. Methods Using the IQVIA Core Diabetes Model, we estimated the impact of maintaining glycated hemoglobin (HbA1c) at 7% (53 mmol/mol) or reducing it by 1% (11 mmol/mol) on total CO2e/patient and CO2e/life-year (LY). Two different cohorts were investigated: those on first-line medical therapy (cohort 1) and those on third-line therapy (cohort 2). CO2e was estimated using cost inputs converted to carbon inputs using the UK National Health Service’s carbon intensity factor. The model was run over a 50-year time horizon, discounting total costs and quality adjusted life years (QALYs) up to 5% and CO2e at 0%. Results Maintaining HbA1c at 7% (53 mmol/mol) reduced total CO2e/patient by 18% (1546 kgCO2e/patient) vs 13% (937 kgCO2e/patient) in cohorts 1 and 2, respectively, and led to a reduction in CO2e/LY gain of 15%–20%. Reducing HbA1c by 1% (11 mmol/mol) caused a 12% (cohort 1) and 9% (cohort 2) reduction in CO2e/patient with a CO2e/LY gain reduction of 11%–14%. Conclusions When comparing people with untreated diabetes, maintaining glycemic control at 7% (53 mmol/mol) on a single agent or improving HbA1c by 1% (11 mmol/mol) by the addition of more glucose-lowering treatment was associated with a reduction in carbon emissions

    Curr Diab Rep

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    Purpose of ReviewTo identify a common effect of health information technologies (HIT) on the management of cardiovascular disease (CVD) risk factors among people with type 2 diabetes (T2D) across randomized control trials (RCT).Recent FindingsCVD is the most frequent cause of morbidity and mortality among patients with diabetes. HIT are effective in reducing HbA1c; however, their effect on cardiovascular risk factor management for patients with T2D has not been evaluated.SummaryWe identified 21 eligible studies (23 estimates) with measurement of SBP, 20 (22 estimates) of DBP, 14 (17 estimates) of HDL, 14 (17 estimates) of LDL, 15 (18 estimates) of triglycerides, and 10 (12 estimates) of weight across databases. We found significant reductions in SBP, DBP, LDL, and TG, and a significant improvement in HDL associated with HIT. As adjuvants to standard diabetic treatment, HIT can be effective tools for improving CVD risk factors among patients with T2D, especially in those whose CVD risk factors are not at goal.Electronic supplementary materialThe online version of this article (10.1007/s11892-019-1152-3) contains supplementary material, which is available to authorized users.1P30DK092950/National Institute of Diabetes and Digestive and Kidney Diseases/2019-04-27T00:00:00Z31030289PMC6486904628
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