Long-term effects and effect heterogeneity of lifestyle and metformin interventions on type 2 diabetes incidence over 21 years in the US Diabetes Prevention Program randomised clinical trial.

Background: In the US Diabetes Prevention Program (DPP), a 3-year randomised clinical trial in 3234 adults with prediabetes, type 2 diabetes incidence was reduced by 58% with intensive lifestyle intervention (ILS) and by 31% with metformin, compared with placebo. We sought to assess the long-term effects and potential heterogeneity of treatment effects over approximately 21 years of follow-up.

Methods: The DPP trial was continued with protocol modifications as the DPP Outcomes Study (DPPOS).

The Diabetes Prevention Program and Its Outcomes Study: NIDDK's Journey Into the Prevention of Type 2 Diabetes and Its Public Health Impact.

The current-day epidemic of type 2 diabetes, largely driven by increased adiposity and reduced physical activity in the setting of genetic susceptibility, is a major public health challenge. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) presciently proposed the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial, designed by investigators in conjunction with NIDDK staff and initiated in 1996. The primary goal of DPP was to determine whether an intensive lifestyle intervention (ILS) or metformin in comparison with placebo would reduce the development of diabetes in a high-risk population with prediabetes.

The NIDDK Takes on the Complications of Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study.

In the Diabetes Control and Complications Trial (DCCT) (1983-1993), intensive therapy aimed at near-normal glycemia was compared with conventional therapy in 1,441 adolescent and adult participants with type 1 diabetes (T1D) over a mean follow-up of 6.5 years. The primary DCCT results, reported in 1993, demonstrated the benefits of intensive therapy (mean HbA1c ∼7%) compared with conventional therapy (HbA1c ∼9%) in reducing the risk of development and progression of microvascular complications by 35%-76%.

Multivitamins After Myocardial Infarction in Patients With Diabetes: A Randomized Clinical Trial.

Importance: In 2013, the Trial to Assess Chelation Therapy (TACT) reported that in 1708 patients with stable coronary disease and prior myocardial infarction (MI), oral multivitamins and multiminerals (OMVMs), in a factorial design with edetate disodium (EDTA) chelation therapy, did not reduce cardiovascular events relative to placebo OMVMs, but active EDTA combined with active OMVMs was superior to placebo OMVM/placebo EDTA.

Objective: To compare OMVM vs placebo in terms of efficacy for reducing major adverse cardiovascular events in patients with diabetes and prior MI.

Design, Setting, And Participants: The TACT2 randomized, multicenter double-masked 2 × 2 factorial clinical trial took place across 88 sites in the US and Canada.

Relationship Between Average Glucose Levels and HbA1c Differs Across Racial Groups: A Substudy of the GRADE Randomized Trial.

Objective: To determine whether the relationship between average glucose (AG) levels and hemoglobin A1c (HbA1c) differs across racial/ethnic groups.

Research Design And Methods: We performed a prospective substudy of GRADE, a comparative effectiveness randomized trial conducted in 36 centers in the U.S.

Within and post-trial effects of an intensive lifestyle intervention on kidney disease in adults with overweight or obesity and type 2 diabetes mellitus: a secondary analysis of the Look AHEAD clinical trial.

Introduction: The Look AHEAD randomized clinical trial reported that an 8-year intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) in adults aged 45-76 years with type 2 diabetes and overweight/obesity delayed kidney disease progression. Here, we report long-term post-intervention follow-up for the trial's secondary outcome of kidney disease.

Research Design And Methods: We examined effects of ILI (n=2570) versus DSE (n=2575) on decline in estimated glomerular filtration rate (eGFR) to <45 mL/min/1.

Concussion burden and later-life cardiovascular risk factors in former professional American-style football players.

Objective: Mid-life cardiovascular risk factors are associated with later cognitive decline. Whether repetitive head injury among professional athletes impacts cardiovascular risk is unknown. We investigated associations between concussion burden and postcareer hypertension, high cholesterol, and diabetes among former professional American-style football (ASF) players.

Baseline characteristics including blood and urine metal levels in the Trial to Assess Chelation Therapy 2 (TACT2).

Background: The reduction in cardiovascular disease (CVD) events with edetate disodium (EDTA) in the Trial to Assess Chelation Therapy (TACT) suggested that chelation of toxic metals might provide novel opportunities to reduce CVD in patients with diabetes. Lead and cadmium are vasculotoxic metals chelated by EDTA. We present baseline characteristics for participants in TACT2, a randomized, double-masked, placebo-controlled trial designed as a replication of the TACT trial limited to patients with diabetes.

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.

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus.

Background: Numerous laboratory tests are used in the diagnosis and management of diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially.

Approach: An expert committee compiled evidence-based recommendations for laboratory analysis in screening, diagnosis, or monitoring of diabetes.

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus.

Background: Numerous laboratory tests are used in the diagnosis and management of diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially.

Approach: An expert committee compiled evidence-based recommendations for laboratory analysis in screening, diagnosis, or monitoring of diabetes.

Executive Summary: Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus.

Background: Numerous laboratory tests are used in the diagnosis and management of patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially. An expert committee compiled evidence-based recommendations for laboratory analysis in patients with diabetes.

Optimal Frequency of Urinary Albumin Screening in Type 1 Diabetes.

Objective: Kidney disease screening recommendations include annual urine testing for albuminuria after 5 years' duration of type 1 diabetes. We aimed to determine a simple, risk factor-based screening schedule that optimizes early detection and testing frequency.

Research Design And Methods: Urinary albumin excretion measurements from 1,343 participants in the Diabetes Control and Complications Trial and its long-term follow-up were used to create piecewise-exponential incidence models assuming 6-month constant hazards.

Glycemia Reduction in Type 2 Diabetes - Microvascular and Cardiovascular Outcomes.

Background: Data are lacking on the comparative effectiveness of commonly used glucose-lowering medications, when added to metformin, with respect to microvascular and cardiovascular disease outcomes in persons with type 2 diabetes.

Methods: We assessed the comparative effectiveness of four commonly used glucose-lowering medications, added to metformin, in achieving and maintaining a glycated hemoglobin level of less than 7.0% in participants with type 2 diabetes.

Cardiometabolic Risk Factors and Incident Cardiovascular Disease Events in Women vs Men With Type 1 Diabetes.

Importance: The lower risk of cardiovascular disease (CVD) among women compared with men in the general population may be diminished among those with diabetes.

Objective: To evaluate cardiometabolic risk factors and their management in association with CVD events in women vs men with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.

Design, Setting, And Participants: This cohort study used data obtained during the combined DCCT (randomized clinical trial, conducted 1983-1993) and EDIC (observational study, conducted 1994 to present) studies through April 30, 2018 (mean [SD] follow-up, 28.

Association of Estimated Time-in-Range Capillary Glucose Levels Versus HbA1c With Progression of Microvascular Complications in the Diabetes Control and Complications Trial.

Objective: Estimated time in range (eTIR) obtained from DCCT glucose profiles (pre- and postprandial and bedtime) was recently reported to be associated with microvascular outcomes and was recommended as a clinical trial outcome, but without consideration of HbA1c.

Research Design And Methods: The associations of eTIR with diabetic retinopathy and microalbuminuria were assessed without and with adjustment for HbA1c and baseline covariates.

Results: Adjusted for HbA1c and covariates, eTIR was marginally significantly associated with retinopathy in the full cohort (hazard ratio [HR] 1.