Mortality Outcomes in a Large Population with and without Covert Cerebrovascular Disease.

Covert cerebrovascular disease (CCD) is frequently reported on neuroimaging and associates with increased dementia and stroke risk. We aimed to determine how incidentally-discovered CCD during clinical neuroimaging in a large population associates with mortality. We screened CT and MRI reports of adults aged ≥50 in the Kaiser Permanente Southern California health system who underwent neuroimaging for a non-stroke clinical indication from 2009-2019.

Effect of vitamin D on regression to normal glucose regulation and individual glycemic measures: A secondary analysis among participants adherent to the trial protocol in the randomized clinical trial vitamin D and type 2 diabetes (D2d) study.

Aims: To examine the effect of vitamin D on regression to normal glucose regulation (NGR) and individual glycemic measures in the D2d study.

Methods: In per-protocol analyses, we examined time to new-onset diabetes; time to new-onset NGR defined as first occurrence of: 2-or-3 glycemic criteria in the normal range (NGR-1) or fasting plasma glucose (FPG) and 2-hour post-load-glucose (2hPG) in the normal range (NGR-2); proportion meeting NGR at the last study visit; and change in FPG, 2hPG, and HbA1c.

Results: Among 2423 participants, hazard ratio [HR] for diabetes was 0.

Indices of hepatic steatosis and fibrosis in prediabetes and association with diabetes development in the vitamin D and type 2 diabetes study.

Aims: Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity that leads to poor outcomes in people at high risk for development of type 2 diabetes (T2D). Vitamin D is a possible mediator. In the vitamin D and type 2 diabetes study (D2d), we investigated the relationship of baseline indices of NAFLD with incident T2D and whether the effect of vitamin D on diabetes was modified by NAFLD.

Effect of intratrial mean 25(OH)D concentration on diabetes risk, by race and weight: an ancillary analysis in the D2d study.

Background: Higher serum 25-hydroxyvitamin D [25(OH)D] is associated with lower type 2 diabetes risk. 25(OH)D varies due to skin pigmentation and weight.

Objectives: This analysis aims to determine whether the effect of vitamin D differs among people of color and those with overweight/obesity (who have higher diabetes risk) compared with individuals who are White or have normal weight.

Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials.

Background: The role of vitamin D in people who are at risk for type 2 diabetes remains unclear.

Purpose: To evaluate whether administration of vitamin D decreases risk for diabetes among people with prediabetes.

Data Sources: PubMed, Embase, and ClinicalTrials.

Development of Parkinson Disease and Its Relationship with Incidentally Discovered White Matter Disease and Covert Brain Infarction in a Real-World Cohort.

Objective: This study aimed to examine the relationship between covert cerebrovascular disease, comprised of covert brain infarction and white matter disease, discovered incidentally in routine care, and subsequent Parkinson disease.

Methods: Patients were ≥50 years and received neuroimaging for non-stroke indications in the Kaiser Permanente Southern California system from 2009 to 2019. Natural language processing identified incidentally discovered covert brain infarction and white matter disease and classified white matter disease severity.

The effect of vitamin D supplementation on cardiovascular risk in patients with prediabetes: A secondary analysis of the D2d study.

Aims: Low blood 25(OH)D level is associated with increased cardiovascular disease (CVD) risk. Additionally, individuals with prediabetes are at higher risk for CVD than individuals with normoglycemia. We investigated the effects of vitamin D supplementation on CVD outcomes in the vitamin D and type 2 diabetes (D2d) study, a large trial among adults with prediabetes.

Safety and tolerability of high-dose daily vitamin D supplementation in the vitamin D and type 2 diabetes (D2d) study-a randomized trial in persons with prediabetes.

Background/objectives: Routine use of vitamin D supplements has increased substantially in the United States. However, the safety and tolerability of long-term use of high-dose vitamin D are not known. We assessed the safety and tolerability of high-dose, daily vitamin D in the vitamin D and type 2 diabetes (D2d) study.

Effect of Vitamin D Supplementation on Kidney Function in Adults with Prediabetes: A Secondary Analysis of a Randomized Trial.

Background And Objectives: Low serum 25-hydroxyvitamin D (25[OH]D) concentration has been associated with higher levels of proteinuria and lower levels of eGFR in observational studies. In the Vitamin D and Type 2 Diabetes (D2d) study, we investigated the effect of vitamin D supplementation on kidney outcomes in a population with prediabetes.

Design, Setting, Participants, & Measurements: Overweight/obese adults with high risk for type 2 diabetes (defined by meeting two of three glycemic criteria for prediabetes) were randomized to vitamin D 4000 IU per day versus placebo.

Vitamin D Supplementation for Prevention of Cancer: The D2d Cancer Outcomes (D2dCA) Ancillary Study.

Context: Observational studies suggest that low vitamin D status may be a risk factor for cancer.

Objective: In a population with prediabetes and overweight/obesity that is at higher risk of cancer than the general population, we sought to determine if vitamin D supplementation lowers the risk of cancer and precancers.

Methods: The Vitamin D and type 2 diabetes (D2d) cancer outcomes study (D2dCA) is an ancillary study to the D2d study, which was conducted at 22 academic medical centers in the United States.

Intratrial Exposure to Vitamin D and New-Onset Diabetes Among Adults With Prediabetes: A Secondary Analysis From the Vitamin D and Type 2 Diabetes (D2d) Study.

Objective: Postrandomization biases may influence the estimate of efficacy of supplemental vitamin D in diabetes prevention trials. In the Vitamin D and Type 2 Diabetes (D2d) study, repeated measures of serum 25-hydroxyvitamin D [25(OH)D] level provided an opportunity to test whether intratrial vitamin D exposure affected diabetes risk and whether the effect was modified by trial assignment (vitamin D vs. placebo).

Vitamin D Supplementation and Prevention of Type 2 Diabetes.

Background: Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown.

Methods: We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.

Establishing an electronic health record-supported approach for outreach to and recruitment of persons at high risk of type 2 diabetes in clinical trials: The vitamin D and type 2 diabetes (D2d) study experience.

Aims: To establish recruitment approaches that leverage electronic health records in multicenter prediabetes/diabetes clinical trials and compare recruitment outcomes between electronic health record-supported and conventional recruitment methods.

Methods: Observational analysis of recruitment approaches in the vitamin D and type 2 diabetes (D2d) study, a multicenter trial in participants with prediabetes. Outcomes were adoption of electronic health record-supported recruitment approaches by sites, number of participants screened, recruitment performance (proportion screened who were randomized), and characteristics of participants from electronic health record-supported versus non-electronic health record methods.

One-year outcomes of out-of-hospital administration of intravenous glucose, insulin, and potassium (GIK) in patients with suspected acute coronary syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care] Trial).

The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefits. Here we report 1-year outcomes. Prespecified 1-year end points of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF).

A community consultation survey to evaluate support for and success of the IMMEDIATE trial.

Background: The IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care) Trial, a randomized controlled double-blind clinical effectiveness trial of glucose-insulin-potassium (GIK) administered in ambulances in the out-of-hospital setting, used the Exception from Informed Consent Requirements (EFIC) for Emergency Research under Title 21 of the Code of Federal Regulations. EFIC requirements include community consultation that typically involves using a variety of communication methods and venues to inform the public of the research and to receive their feedback. Although not the primary purpose of the community consultation process, a common concern to research sponsors, staff, and institutional review boards (IRBs) is whether there will be a sufficient number of participants to justify mounting a study in their community.