Subclassification of obesity for precision prediction of cardiometabolic diseases.

Obesity and cardiometabolic disease often, but not always, coincide. Distinguishing subpopulations within which cardiometabolic risk diverges from the risk expected for a given body mass index (BMI) may facilitate precision prevention of cardiometabolic diseases. Accordingly, we performed unsupervised clustering in four European population-based cohorts (N ≈ 173,000).

Prevalence and predictors of female sexual dysfunction among sexually active women in the diabetes prevention program outcomes study.

Objective: To determine the burden and identify correlates of female sexual dysfunction (FSD) among women with prediabetes (PreD) and type 2 diabetes (T2D) enrolled in the Diabetes Prevention Program (DPP) Outcomes Study (DPPOS).

Methods: The DPPOS visit included the Female Sexual Function Index (FSFI) to determine sexual function. Of 1464 participants, 1320 (90%) completed the (FSFI) and 426 were sexually active.

Prevalence and predictors of erectile dysfunction among men in the diabetes prevention program outcomes study.

Objective: To determine burden and identify correlates of erectile dysfunction (ED) among men with prediabetes (PreD) and type 2 diabetes (T2D) enrolled in the Diabetes Prevention Program (DPP) Outcomes Study (DPPOS).

Research Design And Methods: The 2017 DPPOS visit included administration of the International Index of Erectile Function. Of 648 male participants, 88 % (n = 568) completed the survey.

Coronary Artery Calcium and Cognitive Decline in the Diabetes Prevention Program Outcomes Study.

Background Our aim was to investigate the association of coronary artery calcium (CAC) with cognitive function in adults with impaired glucose tolerance or type 2 diabetes. Methods and Results The Diabetes Prevention Program was a randomized controlled trial comparing an intensive lifestyle intervention, metformin, or placebo for prevention of type 2 diabetes among patients with prediabetes. After 3 years, intensive lifestyle intervention and placebo were stopped, the metformin arm was unmasked, and participants continued in the DPPOS (Diabetes Prevention Program Outcomes Study).

Effects of metformin and intensive lifestyle interventions on the incidence of kidney disease in adults in the DPP/DPPOS.

Aims: We analyzed the incidence of kidney disease in the Diabetes Prevention Program Outcomes Study (DPPOS) by originally randomized treatment group assignment: Intensive Lifestyle (ILS), Metformin (MET) or Placebo (PLB).

Methods: The current analyses used a time-to-event approach in which the primary outcome was kidney disease, ascertained as urine albumin-to-creatinine ratio (ACR) ≥ 3.39 mg/mmol (30 mg/g) or eGFR <45 mL/min/1.

Effects of Long-term Metformin and Lifestyle Interventions on Cardiovascular Events in the Diabetes Prevention Program and Its Outcome Study.

Background: Lifestyle intervention and metformin have been shown to prevent diabetes; however, their efficacy in preventing cardiovascular disease associated with the development of diabetes is unclear. We examined whether these interventions reduced the incidence of major cardiovascular events over a 21-year median follow-up of participants in the DPP trial (Diabetes Prevention Program) and DPPOS (Diabetes Prevention Program Outcomes Study).

Methods: During DPP, 3234 participants with impaired glucose tolerance were randomly assigned to metformin 850 mg twice daily, intensive lifestyle or placebo, and followed for 3 years.

Risk of Severe COVID-19 Disease and the Pandemic's Impact on Service Utilization Among a Longitudinal Cohort of Persons with HIV-Washington, DC.

People with HIV (PWH) have a high burden of medical comorbidities, potentially putting them at increased risk for severe COVID-19. Additionally, during the COVID-19 pandemic, HIV care delivery has been restructured and the impact on HIV outcomes is unknown. The objectives of this study were first, to examine the risk of severe COVID-19 among PWH, using a definition incorporating clinical risk factors, and second, to examine the pandemic's impact on HIV care.

Short Communication:Outcomes of Dual Versus Triple Antiretroviral Drug Regimens Among Virally Suppressed Adults in the DC Cohort.

This study explored virological outcomes of two-drug (2DRs) and three-drug (3DRs) antiretroviral regimens in adults with HIV in the DC Cohort. We analyzed 310 treatment-experienced adults with sustained HIV RNA ≤50 copies/mL at baseline, 53 of whom switched to 2DRs and 257 continued 3DRs. Adults on 2DRs and 3DRs had similar demographics (median age 53.

Comparison of ETDRS 7-Field to 4-Widefield Digital Imaging in the Evaluation of Diabetic Retinopathy Severity.

Purpose: To compare Early Treatment Diabetic Retinopathy Study (ETDRS) severity levels between two digital fundus imaging protocols for research studies of diabetic retinopathy: the gold standard 7-field (7F) imaging and the more recent 4-widefield (4W) imaging.

Methods: Two hundred twenty-two participants enrolled in the Diabetes Prevention Program Outcomes Study underwent concurrent 7F and 4W imaging. The ETDRS levels from 220 paired gradable images were determined by masked graders.

Effect of Metformin and Lifestyle Interventions on Mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study.

Objective: To determine whether metformin or lifestyle modification can lower rates of all-cause and cause-specific mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study.

Research Design And Methods: From 1996 to 1999, 3,234 adults at high risk for type 2 diabetes were randomized to an intensive lifestyle intervention, masked metformin, or placebo. Placebo and lifestyle interventions stopped in 2001, and a modified lifestyle program was offered to everyone, but unmasked study metformin continued in those originally randomized.

Long-term effects of lifestyle and metformin interventions in DPP on bone density.

Unlabelled: In the Diabetes Prevention Program Outcome Study (DPPOS), a cohort at high risk of diabetes, randomization to intensive lifestyle intervention or metformin, both associated with weight loss, did not have long-term negative effects on BMD compared with the placebo group. Potential positive effects of metformin on bone warrant further investigation.

Introduction: Randomization to lifestyle intervention (ILS) or metformin in the Diabetes Prevention Program (DPP) resulted in weight loss and reduced progression to diabetes.

COMETS Analytics: An Online Tool for Analyzing and Meta-Analyzing Metabolomics Data in Large Research Consortia.

Consortium-based research is crucial for producing reliable, high-quality findings, but existing tools for consortium studies have important drawbacks with respect to data protection, ease of deployment, and analytical rigor. To address these concerns, we developed COnsortium of METabolomics Studies (COMETS) Analytics to support and streamline consortium-based analyses of metabolomics and other -omics data. The application requires no specialized expertise and can be run locally to guarantee data protection or through a Web-based server for convenience and speed.

Predictive utilities of lipid traits, lipoprotein subfractions and other risk factors for incident diabetes: a machine learning approach in the Diabetes Prevention Program.

Introduction: Although various lipid and non-lipid analytes measured by nuclear magnetic resonance (NMR) spectroscopy have been associated with type 2 diabetes, a structured comparison of the ability of NMR-derived biomarkers and standard lipids to predict individual diabetes risk has not been undertaken in larger studies nor among individuals at high risk of diabetes.

Research Design And Methods: Cumulative discriminative utilities of various groups of biomarkers including NMR lipoproteins, related non-lipid biomarkers, standard lipids, and demographic and glycemic traits were compared for short-term (3.2 years) and long-term (15 years) diabetes development in the Diabetes Prevention Program, a multiethnic, placebo-controlled, randomized controlled trial of individuals with pre-diabetes in the USA (N=2590).

Hepatic Fat in Participants With and Without Incident Diabetes in the Diabetes Prevention Program Outcome Study.

Context: There is little information about fatty liver in prediabetes as it transitions to early diabetes.

Objective: This study is aimed at evaluating the prevalence and determinants of fatty liver in the Diabetes Prevention Program (DPP).

Methods: We measured liver fat as liver attenuation (LA) in Hounsfield units (HU) in 1876 participants at ~14 years following randomization into the DPP, which tested the effects of lifestyle or metformin interventions versus standard care to prevent diabetes.

Per- and polyfluoroalkyl substance plasma concentrations and metabolomic markers of type 2 diabetes in the Diabetes Prevention Program trial.

Background: Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals, some of which have been linked to type 2 diabetes. We tested whether PFAS concentrations were cross-sectionally associated with metabolites previously shown to predict incident type 2 diabetes using the Diabetes Prevention Program (DPP), a trial of individuals at high risk of type 2 diabetes.

Methods: We evaluated 691 participants enrolled in the DPP with baseline measures of 10 PFAS (including total perfluorooctanesulfonic acid (PFOS), total perfluorooctanoic acid (PFOA), and Sb-PFOA [branched isomers of PFOA]) and 77 metabolites.

Infertility, Gravidity, and Risk Of Diabetes among High-Risk Women in the Diabetes Prevention Program Outcomes Study.

Objective: The extent to which infertility and pregnancy independently increase risk of diabetes and subclinical atherosclerosis is not known.

Research Design And Methods: We conducted a secondary analysis of Diabetes Prevention Program (DPP) and the DPP Outcomes Study over a 15-year period. We included women who answered questions about gravidity and infertility at baseline (n = 2085).

Metabolite Profiles of Incident Diabetes and Heterogeneity of Treatment Effect in the Diabetes Prevention Program.

Novel biomarkers of type 2 diabetes (T2D) and response to preventative treatment in individuals with similar clinical risk may highlight metabolic pathways that are important in disease development. We profiled 331 metabolites in 2,015 baseline plasma samples from the Diabetes Prevention Program (DPP). Cox models were used to determine associations between metabolites and incident T2D, as well as whether associations differed by treatment group (i.

Metabolomics Analytics Workflow for Epidemiological Research: Perspectives from the Consortium of Metabolomics Studies (COMETS).

The application of metabolomics technology to epidemiological studies is emerging as a new approach to elucidate disease etiology and for biomarker discovery. However, analysis of metabolomics data is complex and there is an urgent need for the standardization of analysis workflow and reporting of study findings. To inform the development of such guidelines, we conducted a survey of 47 cohort representatives from the Consortium of Metabolomics Studies (COMETS) to gain insights into the current strategies and procedures used for analyzing metabolomics data in epidemiological studies worldwide.

Does diabetes prevention translate into reduced long-term vascular complications of diabetes?

The global epidemic of type 2 diabetes has prompted numerous studies and public health efforts to reduce its development. A variety of interventions, including lifestyle modifications and pharmacological agents directed at ameliorating the major risk factors for type 2 diabetes, are of proven efficacy in reducing the development of type 2 diabetes in people with impaired glucose tolerance. While prevention of the hyperglycaemia characteristic of diabetes is arguably an important, clinically relevant outcome, a more compelling outcome with greater clinical significance is the prevention or reduction of the relatively diabetes-specific microvascular and less-specific cardiovascular disease (CVD) complications associated with diabetes.

The Consortium of Metabolomics Studies (COMETS): Metabolomics in 47 Prospective Cohort Studies.

The Consortium of Metabolomics Studies (COMETS) was established in 2014 to facilitate large-scale collaborative research on the human metabolome and its relationship with disease etiology, diagnosis, and prognosis. COMETS comprises 47 cohorts from Asia, Europe, North America, and South America that together include more than 136,000 participants with blood metabolomics data on samples collected from 1985 to 2017. Metabolomics data were provided by 17 different platforms, with the most frequently used labs being Metabolon, Inc.

Sex Hormones and Measures of Kidney Function in the Diabetes Prevention Program Outcomes Study.

Context: Despite sex differences in chronic kidney disease (CKD) onset and progression, it is unclear whether endogenous sex hormones are associated with kidney function in persons without CKD.

Design And Methods: We conducted a secondary analysis of the Diabetes Prevention Program (DPP) and its follow-up observational study, the DPP Outcomes Study, over 11 years. Participants included overweight and glucose-intolerant men (n = 889) and pre- and postmenopausal women (n = 1281) not using exogenous sex hormones and whose urine albumin-to-creatinine ratio (ACR) was <30 mg/g and normal estimated glomerular filtration ratio (eGFR) was ≥60 mL/min/1.

Non-traditional biomarkers and incident diabetes in the Diabetes Prevention Program: comparative effects of lifestyle and metformin interventions.

Aims/hypothesis: 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.