Increased Genetic Risk for β-Cell Failure Is Associated With β-Cell Function Decline in People With Prediabetes.

Partitioned polygenic scores (pPS) have been developed to capture pathophysiologic processes underlying type 2 diabetes (T2D). We investigated the association of T2D pPS with diabetes-related traits and T2D incidence in the Diabetes Prevention Program. We generated five T2D pPS (β-cell, proinsulin, liver/lipid, obesity, lipodystrophy) in 2,647 participants randomized to intensive lifestyle, metformin, or placebo arms.

Prevalence of Distal Symmetrical Polyneuropathy by Diabetes Prevention Program Treatment Group, Diabetes Status, Duration of Diabetes, and Cumulative Glycemic Exposure.

Objective: To assess associations between distal symmetric polyneuropathy (DSPN) and Diabetes Prevention Program (DPP) treatment groups, diabetes status or duration, and cumulative glycemic exposure approximately 21 years after DPP randomization.

Research Design And Methods: In the DPP, 3,234 adults ≥25 years old at high risk for diabetes were randomized to an intensive lifestyle (ILS), metformin, or placebo intervention to prevent diabetes. After the DPP ended, 2,779 joined the Diabetes Prevention Program Outcomes Study (DPPOS).

Association of Metformin With the Development of Age-Related Macular Degeneration.

Importance: Age-related macular degeneration (AMD) is a leading cause of blindness with no treatment available for early stages. Retrospective studies have shown an association between metformin and reduced risk of AMD.

Objective: To investigate the association between metformin use and age-related macular degeneration (AMD).

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.

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.

Diabetes in ageing: pathways for developing the evidence base for clinical guidance.

Older adults with diabetes are heterogeneous in their medical, functional, and cognitive status, and require careful individualisation of their treatment regimens. However, in the absence of detailed information from clinical trials involving older people with varying characteristics, there is little evidence-based guidance, which is a notable limitation of current approaches to care. It is important to recognise that older people with diabetes might vary in their profiles according to age category, functional health, presence of frailty, and comorbidity profiles.

Precision Medicine in Diabetes: A Consensus Report From the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

The convergence of advances in medical science, human biology, data science, and technology has enabled the generation of new insights into the phenotype known as "diabetes." Increased knowledge of this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence, and how best practice in treatment varies between populations. In parallel, focus has been placed on the development of tools for the application of precision medicine to numerous conditions.

Precision medicine in diabetes: a Consensus Report from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

The convergence of advances in medical science, human biology, data science and technology has enabled the generation of new insights into the phenotype known as 'diabetes'. Increased knowledge of this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence and how best practice in treatment varies between populations. In parallel, focus has been placed on the development of tools for the application of precision medicine to numerous conditions.

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.

Identification of Hip BMD Loss and Fracture Risk Markers Through Population-Based Serum Proteomics.

Serum proteomics analysis may lead to the discovery of novel osteoporosis biomarkers. The Osteoporotic Fractures in Men (MrOS) study comprises men ≥65 years old in the US who have had repeated BMD measures and have been followed for incident fracture. High-throughput quantitative proteomic analysis was performed on baseline fasting serum samples from non-Hispanic white men using a multidimensional approach coupling liquid chromatography, ion-mobility separation, and mass spectrometry (LC-IMS-MS).

Comparing identified and statistically significant lipids and polar metabolites in 15-year old serum and dried blood spot samples for longitudinal studies.

Rationale: The use of dried blood spots (DBS) has many advantages over traditional plasma and serum samples such as the smaller blood volume required, storage at room temperature, and ability to sample in remote locations. However, understanding the robustness of different analytes in DBS samples is essential, especially in older samples collected for longitudinal studies.

Methods: Here we analyzed the stability of polar metabolites and lipids in DBS samples collected in 2000-2001 and stored at room temperature.

Obesity and Falls in a Prospective Study of Older Men: The Osteoporotic Fractures in Men Study.

Objective: The aim of this study is to evaluate fall rates across body mass index (BMI) categories by age group, considering physical performance and comorbidities.

Method: In the Osteoporotic Fractures in Men (MrOS) study, 5,834 men aged ≥65 reported falls every 4 months over 4.8 (±0.

Serum 25-hydroxyvitamin D level and incident type 2 diabetes in older men, the Osteoporotic Fractures in Men (MrOS) study.

The association between vitamin D status and diabetes risk is inconsistent among observational studies, and most of the available studies have been with women. In the present study we investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and incident type 2 diabetes (T2D) in older men (≥65years old) who participated in the multisite Osteoporotic Fractures in Men (MrOS) study enrolled from March 2000 to April 2002. Baseline 25(OH)D levels were available in 1939 subjects without prevalent T2D.

Free 25-Hydroxyvitamin D: Impact of Vitamin D Binding Protein Assays on Racial-Genotypic Associations.

Context: Total 25-hydroxyvitamin D (25OHD) is a marker of vitamin D status and is lower in African Americans than in whites. Whether this difference holds for free 25OHOD (f25OHD) is unclear, considering reported genetic-racial differences in vitamin D binding protein (DBP) used to calculate f25OHD.

Objectives: Our objective was to assess racial-geographic differences in f25OHD and to understand inconsistencies in racial associations with DBP and calculated f25OHD.

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk.

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass.

Evaluation of the Usefulness of Consensus Definitions of Sarcopenia in Older Men: Results from the Observational Osteoporotic Fractures in Men Cohort Study.

Objective: To evaluate the associations between definitions of sarcopenia and clinical outcomes and the ability of the definitions to discriminate those with a high likelihood of having these outcomes from those with a low likelihood.

Design: Osteoporotic Fractures in Men Study.

Setting: Six clinical centers.

Gait Speed Predicts Incident Disability: A Pooled Analysis.

Background: Functional independence with aging is an important goal for individuals and society. Simple prognostic indicators can inform health promotion and care planning, but evidence is limited by heterogeneity in measures of function.

Methods: We performed a pooled analysis of data from seven studies of 27,220 community-dwelling older adults aged 65 or older with baseline gait speed, followed for disability and mortality.

Greater Skeletal Muscle Fat Infiltration Is Associated With Higher All-Cause and Cardiovascular Mortality in Older Men.

Background: Skeletal muscle fat infiltration (myosteatosis) increases with aging, and has been associated with poor metabolic and musculoskeletal health, independent of overall adiposity. Studies examining the relationship of myosteatosis and mortality among older individuals recruited without regard to their health status are sparse.

Methods: We evaluated the association of peripheral computed tomography measured calf myosteatosis (intermuscular fat and muscle density as a measure of intramuscular fat) with mortality in 1,063 community-dwelling older men.

Associations of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D With Bone Mineral Density, Bone Mineral Density Change, and Incident Nonvertebral Fracture.

Relationships between 1,25-dihydroxyvitamin D (1,25(OH)2 D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)2 D with bone mineral density (BMD), BMD change, and incident non-vertebral fractures in a cohort of older men and compared them with those of 25-hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.

Statins and physical activity in older men: the osteoporotic fractures in men study.

Importance: Muscle pain, fatigue, and weakness are common adverse effects of statin medications and may decrease physical activity in older men.

Objective: To determine whether statin use is associated with physical activity, longitudinally and cross-sectionally.

Design, Setting, And Participants: Men participating in the Osteoporotic Fractures in Men Study (N = 5994), a multicenter prospective cohort study of community-living men 65 years and older, enrolled between March 2000 and April 2002.

Higher 25(OH)D2 is associated with lower 25(OH)D3 and 1,25(OH)2D3.

Context: Despite common use of supplemental vitamin D2 in clinical practice, the associations of serum vitamin D2 concentrations with other vitamin D metabolites and total vitamin D are unclear.

Objective: The aim of the study was to measure vitamin D2 and D3 levels and examine their associations with each other and with total vitamin D.

Design: We performed a cross-sectional analysis of 679 randomly selected participants from the Osteoporotic Fractures in Men Study.

Changes in physical performance in older women according to presence and treatment of diabetes mellitus.

Objectives: To determine whether older women with diabetes mellitus have a greater longitudinal decline in physical performance than those without and whether any decline differs according to insulin sensitizer use.

Design: Prospective cohort study.

Setting: Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela, Pennsylvania.