Haptoglobin phenotype and intensive glycemic control for coronary artery disease risk reduction in people with type two diabetes: The Veterans Affairs Diabetes Trial.

Background: Intensive glycemic control reduced the risk of coronary artery disease (CAD) events among White ACCORD study participants with the haptoglobin (Hp)2-2 phenotype, and not among participants without the Hp2-2 phenotype. It is unknown whether these results persist in a population with more severe diabetes.

Methods: Haptoglobin phenotype was measured in 1746 (97 %) samples from the Veterans Affairs Diabetes Trial (VADT) randomized controlled trial.

Plasma Serotonin 2A Receptor Autoantibodies Predict Rapid, Substantial Decline in Neurocognitive Performance in Older Adult Veterans with TBI.

Aim: Traumatic brain injury (TBI) was associated with increased plasma serotonin 2A receptor (5-HT2AR) autoantibodies in adults who experienced neurodegenerative complications. We tested whether the baseline presence of plasma serotonin 2A receptor (5-HT2AR) autoantibodies was a significant predictor of the two-year rate of cognitive decline in middle-aged and older adult TBI.

Methods: Plasma from thirty-five middle-aged and older adult veterans (mean 65 years old) who had suffered traumatic brain injury was subjected to protein-A affinity chromatography.

Association of low fasting C-peptide levels with cardiovascular risk, visit-to-visit glucose variation and severe hypoglycemia in the Veterans Affairs Diabetes Trial (VADT).

Aims: Low C-peptide levels, indicating beta-cell dysfunction, are associated with increased within-day glucose variation and hypoglycemia. In advanced type 2 diabetes, severe hypoglycemia and increased glucose variation predict cardiovascular (CVD) risk. The present study examined the association between C-peptide levels and CVD risk and whether it can be explained by visit-to-visit glucose variation and severe hypoglycemia.

Generalizability of heterogeneous treatment effects based on causal forests applied to two randomized clinical trials of intensive glycemic control.

Purpose Machine learning is an attractive tool for identifying heterogeneous treatment effects (HTE) of interventions but generalizability of machine learning derived HTE remains unclear. We examined generalizability of HTE detected using causal forests in two similarly designed randomized trials in type II diabetes patients. Methods We evaluated published HTE of intensive versus standard glycemic control on all-cause mortality from the Action to Control Cardiovascular Risk in Diabetes study (ACCORD) in a second trial, the Veterans Affairs Diabetes Trial (VADT).

Fasting Glucose Variation Predicts Microvascular Risk in ACCORD and VADT.

Aims: The association of glycemic variability with microvascular disease complications in type 2 diabetes (T2D) has been under-studied and remains unclear. We investigated this relationship using both Action to Control Cardiovascular Risk in Diabetes (ACCORD) and the Veteran Affairs Diabetes Trial (VADT).

Methods: In ACCORD, fasting plasma glucose (FPG) was measured 1 to 3 times/year for up to 84 months in 10 251 individuals.

Type 2 Diabetes Predicts Increased Risk of Neurodegenerative Complications in Veterans Suffering Traumatic Brain Injury.

Aims: Obese type 2 diabetes and traumatic brain injury are associated with persistent peripheral and neuro-inflammation, respectively. We tested whether adult type 2 diabetes increased the hazard rate for neurodegeneration complications following traumatic brain injury.

Methods: Retrospective chart review of patients treated at the Veterans Affairs New Jersey Healthcare System between 2016-2019 and having a diagnosis of prior traumatic brain injury was performed in adult veterans, age 50 years or older.

Intensive Glucose Control in Patients with Type 2 Diabetes - 15-Year Follow-up.

Background: We previously reported that a median of 5.6 years of intensive as compared with standard glucose lowering in 1791 military veterans with type 2 diabetes resulted in a risk of major cardiovascular events that was significantly lower (by 17%) after a total of 10 years of combined intervention and observational follow-up. We now report the full 15-year follow-up.

Glycaemic variation is a predictor of all-cause mortality in the Veteran Affairs Diabetes Trial.

Diabetes is associated with substantially increased mortality. Classic risk factors explain a portion of the excess of mortality in type 2 diabetes. The aim of this study was to examine whether visit-to-visit variation in fasting glucose and haemoglobin A1c values in the Veteran Affairs Diabetes Trial were associated with all-cause mortality in patients with type 2 diabetes in addition to other comorbidity conditions, hypoglycaemic events and adverse lifestyle behaviours.

Glycemic Variation and Cardiovascular Risk in the Veterans Affairs Diabetes Trial.

Objective: There is uncertainty about the importance of glycemic variability in cardiovascular complications in patients with type 2 diabetes. Using the Veterans Affairs Diabetes Trial (VADT), we investigated the association between variation in fasting glucose and glycated hemoglobin (HbA) over time and the incidence of cardiovascular disease (CVD) and assessed whether this is influenced by intensive or standard glycemic control.

Research Design And Methods: During the VADT, fasting glucose and HbA were measured every 3 months for up to 84 months in 1,791 individuals.

Advanced Glycation End Products, Oxidation Products, and Incident Cardiovascular Events in Patients With Type 2 Diabetes.

Objective: The goal of this study was to determine whether plasma levels of advanced glycation end products (AGE) and oxidation products (OP) predict the incidence of cardiovascular disease (CVD) in type 2 diabetes.

Research Design And Methods: Five specific AGE (methylglyoxal hydroimidazolone, carboxymethyl lysine, carboxyethyl lysine, 3-deoxyglucosone hydroimidazolone, and glyoxal hydroimidazolone) and two OP (2-aminoadipic acid and methionine sulfoxide [MetSO]) were measured at baseline in two intensive glucose-lowering studies: ) a subcohort of the Veterans Affairs Diabetes Trial (VADT) ( = 445) and ) a nested case-control subgroup from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study ( = 271).

Results: Increased levels of several AGE and OP were associated with older age, decreased kidney function, previous CVD, and longer diabetes duration, but not with hemoglobin A.

Long-term follow-up of intensive glycaemic control on renal outcomes in the Veterans Affairs Diabetes Trial (VADT).

Aims/hypothesis: We conducted an analysis of data collected during the Veterans Affairs Diabetes Trial (VADT) and the follow-up study (VADT-F) to determine whether intensive (INT) compared with standard (STD) glycaemic control during the VADT resulted in better long-term kidney outcomes.

Methods: VADT randomly assigned 1791 veterans from 20 Veterans Affairs (VA) medical centres who had type 2 diabetes mellitus and a mean HbA of 9.4 ± 2% (79.

Advanced Glycation End Products, Oxidation Products, and the Extent of Atherosclerosis During the VA Diabetes Trial and Follow-up Study.

Objective: To determine whether plasma levels of advanced glycation end products and oxidation products play a role in the development of atherosclerosis in patients with type 2 diabetes (T2D) over nearly 10 years of the VA Diabetes Trial and Follow-up Study.

Research Design And Methods: Baseline plasma levels of methylglyoxal hydroimidazolone, Nε-carboxymethyl lysine, Nε-carboxyethyl lysine (CEL), 3-deoxyglucosone hydroimidazolone and glyoxal hydroimidazolone (G-H1), 2-aminoadipic acid (2-AAA), and methionine sulfoxide were measured in a total of 411 participants, who underwent ultrasound assessment of carotid intima-media thickness (CIMT), and computed tomography scanning of coronary artery calcification (CAC) and abdominal aortic artery calcification (AAC) after an average of 10 years of follow-up.

Results: In risk factor-adjusted multivariable regression models, G-H1 was associated with the extent of CIMT and CAC.

Predictors of Cognitive Decline in Older Adult Type 2 Diabetes from the Veterans Affairs Diabetes Trial.

Aims: Cognitive decline disproportionately affects older adult type 2 diabetes. We tested whether randomized intensive (INT) glucose-lowering reduces the rate(s) of cognitive decline in adults with advanced type 2 diabetes (mean: age, 60 years; diabetes duration, 11 years) from the Veterans Affairs Diabetes Trial.

Methods: A battery of neuropsychological tests [digit span, digit symbol substitution (DSym), and Trails-making Test-Part B (TMT-B)] was administered at baseline in ~1700 participants and repeated at year 5.

Association of Blood Glucose Control and Lipids With Diabetic Retinopathy in the Veterans Affairs Diabetes Trial (VADT).

Objective: This study examined whether lipids modify the relationship between intensive glucose control (INT) and diabetic retinopathy (DR).

Research Design And Methods: The incidence and progression of DR were assessed in 858 of 1,791 participants with 7-field stereoscopic fundus photographs at baseline and 5 years later.

Results: Odds of DR progression were lower by ∼40% in those with baseline total cholesterol (TC) ≥200 mg/dL (P = 0.

A Link Between Hypoglycemia and Progression of Atherosclerosis in the Veterans Affairs Diabetes Trial (VADT).

Objective: To determine whether a link exists between serious hypoglycemia and progression of atherosclerosis in a substudy of the Veterans Affairs Diabetes Trial (VADT) and to examine whether glycemic control during the VADT modified the association between serious hypoglycemia and coronary artery calcium (CAC) progression.

Research Design And Methods: Serious hypoglycemia was defined as severe episodes with loss of consciousness or requiring assistance or documented glucose <50 mg/dL. Progression of CAC was determined in 197 participants with baseline and follow-up computed tomography scans.

Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes.

Background: The Veterans Affairs Diabetes Trial previously showed that intensive glucose lowering, as compared with standard therapy, did not significantly reduce the rate of major cardiovascular events among 1791 military veterans (median follow-up, 5.6 years). We report the extended follow-up of the study participants.

The effect of intensive glucose lowering therapy among major racial/ethnic groups in the Veterans Affairs Diabetes Trial.

Objective: To examine the effect of intensive glycemic control on cardiovascular disease events (CVD) among the major race/ethnic groups in a post-hoc analysis of the VADT.

Materials And Methods: Participants included 1111 non-Hispanic Whites, 307 Hispanics and 306 non-Hispanic Blacks randomized to intensive or standard glucose treatment in VADT. Multivariable Cox proportional hazards models were constructed to assess the effect of intensive glucose treatment on CVD events among race/ethnic groups.

Blood pressure and pulse pressure effects on renal outcomes in the Veterans Affairs Diabetes Trial (VADT).

Objective: Blood pressure (BP) control for renal protection is essential for patients with type 2 diabetes. Our objective in this analysis of Veterans Affairs Diabetes Trial (VADT) data was to learn whether on-study systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) affected renal outcomes measured as albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR).

Research Design And Methods: The VADT was a prospective, randomized study of 1,791 veterans with type 2 diabetes to determine whether intensive glucose control prevented major cardiovascular events.

Association of blood glucose control and pancreatic reserve with diabetic retinopathy in the Veterans Affairs Diabetes Trial (VADT).

Aims/hypothesis: The aim of this study was to test the hypothesis that intensive glycaemic control (INT) and higher plasma C-peptide levels in patients with poorly controlled diabetes would be associated with better eye outcomes.

Methods: The incidence and progression of diabetic retinopathy (DR) was assessed by grading seven-field stereoscopic fundus photographs at baseline and 5 years later in 858 of 1,791 participants in the Veterans Affairs Diabetes Trial (VADT).

Results: After adjustment for all covariates, risk of progression (but not incidence) of DR increased by 30% for each 1% increase in baseline HbA1c (OR 1.

Association of PAI-1 and fibrinogen with diabetic retinopathy in the Veterans Affairs Diabetes Trial (VADT).

Objective: To test the hypothesis that high levels of plasminogen-activating inhibitor (PAI)-1 and fibrinogen at baseline were associated with the onset or progression of diabetic retinopathy (DR) during the Veterans Affairs Diabetes Trial (VADT).

Research Design And Methods: The VADT was an open-label, prospective, randomized controlled trial to test the effect of standard glycemic control (STD) compared with intensive control (INT) on cardiovascular events in patients with advanced type 2 diabetes mellitus (T2DM). Diabetic retinopathy (DR) outcomes were also collected.

The effect of intensive glucose lowering on lipoprotein particle profiles and inflammatory markers in the Veterans Affairs Diabetes Trial (VADT).

Objective: Intensive glucose-lowering therapy (INT) did not reduce macrovascular events in the recent randomized trials, possibly because it did not improve or worsen other traditional or novel cardiovascular risk factors.

Research Design And Methods: Standard plasma lipids, cholesterol content of lipoprotein subfractions, and plasma inflammatory and prothrombotic markers were determined in a subgroup of the Veterans Affairs Diabetes Trial (VADT) participants (n = 266) at baseline and after 9 months of INT or standard therapy.

Results: INT lowered glycated hemoglobin (by a median of 2% vs.