Project description:<p>The Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial was a randomized, multicenter, double 2 x 2 factorial design study involving 10,251 middle-aged and older participants with type-2 diabetes who are at high risk for CVD events because of existing CVD or additional risk factors. The purpose of ACCORD was to determine if intensive glycemic control, intensive lipid management and intensive blood pressure control could prevent major cardiovascular events (myocardial infarction, stroke or cardiovascular death) in adults with type 2 diabetes mellitus. Secondary hypotheses included treatment differences in other cardiovascular outcomes, total mortality, microvascular outcomes, health-related quality of life and cost-effectiveness.</p> <p>The ACCORD trial failed to show a beneficial effect of intensive blood pressure or lipid therapy on the primary outcome, and intensive glycemia management actually increased mortality. The hypothesis underlying this ancillary study is that the failure of ACCORD to achieve its goal of reducing cardiovascular risk in diabetic patients through intensive management of hyperglycemia, dyslipidemia, and hypertension may be the result of variation in drug response due to genetic variation between individual participants. Benefits of intensive therapy may accrue to subsets of subjects with specific genetic variants predisposing to efficacious responses to particular therapeutic regimens, and harms may accrue to those with other variants predisposing to poor efficacy or adverse events. Identifying these variants could lead to a precision medicine approach to treating diabetes where each patient's genetic profile could identify the most efficacious treatment regimen with the lowest likelihood of adverse events. To test this hypothesis, a genome-wide genetic analysis was undertaken, incorporating both common variants distributed across the genome and rare variants targeted to exonic regions. Associations of genetic variants with short term responses to individual medicines as well as long term outcomes were investigated.</p> <p>The dataset is composed of genetic data from the ~6100 participants who agreed to participate in the ACCORD optional genetic studies and who allowed broad investigator access to their samples and the data derived from those samples, and from whom a DNA sample of sufficient quality was obtained. While a total of 8514 participants consented to the optional genetics studies, not all consented to broad investigator access, and those who did not are not included in this dataset, although they were also genotyped. Access to these additional genotypes can only be obtained by direct collaboration with the investigators of this study. Phenotype data used in the association analyses are derived from the ACCORD public release clinical data set, which has been made available through <a href="https://biolincc.nhlbi.nih.gov/studies/accord/">BioLINCC</a>.</p>
Project description:ObjectiveIntensive therapy targeting normal blood glucose increased mortality compared with standard treatment in a randomized clinical trial of 10,251 participants with type 2 diabetes at high-risk for cardiovascular disease (CVD) events. We evaluated whether the presence of cardiac autonomic neuropathy (CAN) at baseline modified the effect of intensive compared with standard glycemia treatment on mortality outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants.Research design and methodsCAN was assessed by measures of heart rate variability (HRV) and QT index (QTI) computed from 10-s resting electrocardiograms in 8,135 ACCORD trial participants with valid measurements (mean age 63.0 years, 40% women). Prespecified CAN definitions included a composite of the lowest quartile of HRV and highest QTI quartile in the presence or absence of peripheral neuropathy. Outcomes were all-cause and CVD mortality. Associations between CAN and mortality were evaluated by proportional hazards analysis, adjusting for treatment group allocation, CVD history, and multiple prespecified baseline covariates.ResultsDuring a mean 3.5 years follow-up, there were 329 deaths from all causes. In fully adjusted analyses, participants with baseline CAN were 1.55-2.14 times as likely to die as participants without CAN, depending on the CAN definition used (P < 0.02 for all). The effect of allocation to the intensive group on all-cause and CVD mortality was similar in participants with or without CAN at baseline (P(interaction) > 0.7).ConclusionsWhereas CAN was associated with increased mortality in this high-risk type 2 diabetes cohort, these analyses indicate that participants with CAN at baseline had similar mortality outcomes from intensive compared with standard glycemia treatment in the ACCORD cohort.
Project description:BackgroundWe investigated the associations between glycated hemoglobin (HbA1c) trajectories and cardiovascular outcomes using data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study.MethodsWe used HbA1c values within the first 2 years of treatment for modeling with a latent class growth model. Groups of HbA1c trajectories were modeled separately in the standard (group 1-group 4) and intensive (group 5-group 8) treatment arms. The primary outcome in the ACCORD study was a composite of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes. Effects of HbA1c trajectories on cardiovascular outcomes were analyzed using a Cox-proportional hazard model.ResultsBaseline HbA1c levels for the eight trajectories (group 1-group 8) were 7.8 ± 0.8, 8.2 ± 0.9, 9.3 ± 1.1, 9.6 ± 1.2, 7.8 ± 0.7, 10.1 ± 0.8, 8.3 ± 0.7, and 9.5 ± 1.1%, respectively. The respective values after 2 years of treatment were 7.0 ± 0.6, 7.7 ± 0.7, 8.5 ± 0.9, 10.3 ± 1.3, 6.2 ± 0.4, 6.5 ± 0.6, 7.2 ± 0.6, and 8.5 ± 1.1%. After a median follow-up of 4.8 years, group 5 and group 6 had similar outcomes compared with group 1 (reference group). In contrast, group 3, group 4, and group 8 had higher risks of the primary composite outcome compared with group 1.ConclusionHbA1c trajectory was associated with cardiovascular outcomes in type 2 diabetes patients with high cardiovascular risk.
Project description:AimsTo evaluate visual acuity (VA) outcomes of cataract surgery, and factors associated with good visual outcomes, among a population with diabetes.MethodsParticipants with type 2 diabetes enrolled in The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and ACCORD-eye substudy. 1136 eyes of 784 ACCORD participants receiving cataract surgery during follow-up (2001-2014) were included. Of these, 362 eyes had fundus photographs gradable for diabetic retinopathy. The main outcome measure was the achievement of postoperative VA of 20/40 or better.ResultsIn the sample of 1136 eyes, 762 eyes (67.1%) achieved good visual outcome of 20/40 or better. Factors predictive of good visual outcome were higher level of educational attainment (college vs some high school, OR 2.35 (95% CI 1.44 to 3.82)), bilateral cataract surgery (OR 1.55 (1.14 to 2.10)) and preoperative VA (20/20 or better vs worse than 20/200, OR 10.59 (4.07 to 27.54)). Factors not significantly associated (p>0.05) included age, sex, race, smoking, diabetes duration, blood pressure, lipid levels and haemoglobin A1C (HbA1C). In the subsample of 362 eyes, absence of diabetic retinopathy was associated with good visual outcome (OR 1.73 (1.02 to 2.94)).ConclusionAmong individuals with diabetes, two-thirds of eyes achieved good visual outcome after cataract surgery. Notable factors associated with visual outcome included preoperative VA and diabetic retinopathy, but not HbA1C, underscoring that while certain ocular measures may help evaluate visual potential, systemic parameters may not be as valuable. Sociodemographic factors might also be important considerations. Although the current visual prognosis after cataract surgery is usually favourable, certain factors still limit the visual potential in those with diabetes.
Project description:BackgroundGreater lipid variability may cause adverse health events among diabetic patients. We aimed to examine the effect of lipid variability on the risk of diabetic microvascular outcomes among type 2 diabetes mellitus patients.MethodsWe assessed the association between visit-to-visit variability (measured by variability independent of mean) in high-density lipoprotein (HDL) cholesterol, low-density lipoprotein-cholesterol (LDL), triglyceride, and remnant cholesterol (RC) measurements among participants involved in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and the risk of incident microvascular outcomes, including nephropathy, neuropathy, and retinopathy. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for potential confounders.ResultsThere were 2400, 2470, and 2468 cases of nephropathy, neuropathy, and retinopathy during a follow-up period of 22 600, 21 542, and 26 701 person-years, respectively. Higher levels of HDL, triglyceride, and RC variability were associated with an increased risk of incident nephropathy and neuropathy. Compared with the lowest quartile, the fully adjusted HRs (95% CI) for the highest quartile of HDL, triglyceride, and RC variability for nephropathy risk were 1.57 (1.22, 2.01), 1.50 (1.18, 1.92), and 1.40 (1.09, 1.80), respectively; and for neuropathy, the corresponding risks were 1.36 (1.05, 1.75), 1.47 (1.14, 1.91), and 1.35 (1.04, 1.74), respectively. Null association was observed between LDL variability and all microvascular complications. Additionally, all associations of variability in the other lipids with retinopathy risk were null.ConclusionAmong individuals with type 2 diabetes mellitus, HDL, triglyceride, and RC variability were associated with increased risks of nephropathy and neuropathy but not retinopathy.Trial registrationClinicalTrials.gov., no. NCT00000620.