Patricia Feeney

Depression predicts all-cause mortality: Epidemiological evaluation from the ACCORD HRQL substudy

OBJECTIVE Depression affects up to 20–25% of adults with type 2 diabetes and may increase all-cause mortality, but few well-designed studies have examined the effects of depression on the full range of cardiovascular disease outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 2,053 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) Health-Related Quality of Life substudy completed the Patient Health Questionnaire (PHQ)-9 measure of depression symptoms at baseline and 12, 36, and 48 months. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) (95% CI) for the time-varying impact of depression on protocol-defined clinical outcomes with and without adjustment for demographic, trial-related, clinical, and behavioral variables. RESULTS In fully adjusted models, depression was not significantly related to the ACCORD primary composite outcome (cardiovascular death, nonfatal heart attack, or stroke) (HR 1.53 [95% CI 0.85–2.73]) or to the ACCORD microvascular composite outcome (0.93 [0.53–1.62]), but all-cause mortality was significantly increased both in those with PHQ-assessed probable major depression (2.24 [1.24–4.06]) and PHQ score of ≥10 (1.84 [1.17–2.89]). The effect of depression on all-cause mortality was not related to previous cardiovascular events or to assignment to intensive or standard glycemia control. Probable major depression (by PHQ-9) had a borderline impact on the ACCORD macrovascular end point (1.42 [0.99–2.04]). CONCLUSIONS Depression increases the risk of all-cause mortality and may increase the risk of macrovascular events among adults with type 2 diabetes at high risk for cardiovascular events.

Effect of the Look AHEAD Study Intervention on Medication Use and Related Cost to Treat Cardiovascular Disease Risk Factors in individuals With Type 2 Diabetes

OBJECTIVE To examine the effect of a lifestyle intervention to produce weight loss and increased physical fitness on use and cost of medications to treat cardiovascular disease (CVD) risk factors in people with type 2 diabetes. RESEARCH DESIGN AND METHODS Look AHEAD is a multicenter randomized controlled trial of 5,145 overweight or obese individuals with type 2 diabetes, aged 45–76 years. An intensive lifestyle intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education (DSE) condition. Medications prescribed to treat diabetes, hypertension, and hyperlipidemia were compared at baseline and 1 year. Medication costs were conservatively estimated using prices from a national online pharmacy. RESULTS Participants randomized to an ILI had significantly greater improvements in CVD risk parameters and reduced medication use and cost compared with those assigned to DSE. At 1 year, average number of medications prescribed to treat CVD risk factors was 3.1 ± 1.8 for the ILI group and 3.6 ± 1.8 for the DSE group (P < 0.0001), with estimated total monthly medication costs of

Suboptimal control of glycemia, blood pressure, and LDL cholesterol in overweight adults with diabetes : the Look AHEAD Study

143 and

Determinants of Weight Gain in the Action to Control Cardiovascular Risk in Diabetes Trial

173, respectively (P < 0.0001). DSE participants meeting optimal care goals at 1 year were taking an average of 3.8 ± 1.6 medications at an estimated cost of

Effect of intensive glycemic lowering on health-related quality of life in type 2 diabetes: ACCORD trial.

194/month. ILI participants at optimal care required fewer medications (3.2 ± 1.7) at lower cost (

Effect of Intensive Versus Standard Blood Pressure Control on Depression and Health-Related Quality of Life in Type 2 Diabetes: The ACCORD trial

154/month) (P < 0.001). CONCLUSIONS At 1 year, ILI significantly improved CVD risk factors, while at the same time reduced medication use and cost. Continued intervention and follow-up will determine whether these changes are maintained and reduce cardiovascular risk.

Baseline comparison of three health utility measures and the feeling thermometer among participants in the action to control cardiovascular risk in diabetes trial

BACKGROUND The characteristics associated with meeting goals for glycemia, blood pressure (BP), and low-density lipoprotein (LDL) cholesterol for participants with diabetes were examined. METHODS Baseline information on demographics, medical history, and anthropometry, as well as on hemoglobin A1c, BP, and LDL cholesterol levels, was measured in 5145 participants of Look AHEAD, a multicenter randomized trial performed to determine whether long-term weight loss and increased physical fitness reduce cardiovascular disease (CVD) in overweight and obese individuals with type 2 diabetes. Logistic regression was used to analyze these cross-sectional data to ascertain associations between participant characteristics and attainment of risk factor goals [hemoglobin A1c <7.0%, BP <130/80 mmHg, and LDL <100 mg/dl]. RESULTS The study population had a mean age of 58.7 years and a mean body mass index of 36.0 kg/m(2). Of the total number of participants, 59.5% were female, 36.8% were of ethnic/racial minority, and 87.3% were on diabetes medications. Upon enrollment, 45.8% had hemoglobin A1c<7.0%, 51.7% had BP<130/80 mmHg, and 37.2% had LDL<100 mg/dl. All three goals were met by only 10.1%. We found consistent evidence for differences in risk factor control by age, gender, race/ethnicity, degree of obesity, education, income, CVD, source of medical care, and medication use. In multivariable analysis, African-American race, increasing degree of obesity, insulin use, and nonutilization of a lipid-lowering agent were associated with not meeting all risk factor goals. CONCLUSION These data demonstrate that numerous baseline characteristics are associated with suboptimal control of these cardiovascular risk factors among overweight and obese adults with diabetes.

Glycaemia and correlates of patient-reported outcomes in ACCORD trial participants.

OBJECTIVE Identify determinants of weight gain in people with type 2 diabetes mellitus (T2DM) allocated to intensive versus standard glycemic control in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. RESEARCH DESIGN AND METHODS We studied determinants of weight gain over 2 years in 8,929 participants (4,425 intensive arm and 4,504 standard arm) with T2DM in the ACCORD trial. We used general linear models to examine the association between each baseline characteristic and weight change at the 2-year visit. We fit a linear regression of change in weight and A1C and used general linear models to examine the association between each medication at baseline and weight change at the 2-year visit, stratified by glycemia allocation. RESULTS There was significantly more weight gain in the intensive glycemia arm of the trial compared with the standard arm (3.0 ± 7.0 vs. 0.3 ± 6.3 kg). On multivariate analysis, younger age, male sex, Asian race, no smoking history, high A1C, baseline BMI of 25–35, high waist circumference, baseline insulin use, and baseline metformin use were independently associated with weight gain over 2 years. Reduction of A1C from baseline was consistently associated with weight gain only when baseline A1C was elevated. Medication usage accounted for <15% of the variability of weight change, with initiation of thiazolidinedione (TZD) use the most prominent factor. Intensive participants who never took insulin or a TZD had an average weight loss of 2.9 kg during the first 2 years of the trial. In contrast, intensive participants who had never previously used insulin or TZD but began this combination after enrolling in the ACCORD trial had a weight gain of 4.6–5.3 kg at 2 years. CONCLUSIONS Weight gain in ACCORD was greater with intensive than with standard treatment and generally associated with reduction of A1C from elevated baseline values. Initiation of TZD and/or insulin therapy was the most important medication-related factor associated with weight gain.

Constructing common cohorts from trials with overlapping eligibility criteria: Implications for comparing effect sizes between trials

OBJECTIVE To compare the effect of intensive versus standard glycemic control strategies on health-related quality of life (HRQL) in a substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. RESEARCH DESIGN AND METHODS A randomly selected subsample of 2,053 ACCORD participants enrolled in the HRQL substudy was assessed at baseline and 12-, 36-, and 48-month visits. HRQL assessment included general health status (the 36-Item Short Form Health Survey [SF-36]), diabetes symptoms (the Diabetes Symptom Distress Checklist), depression (Patient Health Questionnaire [PHQ]-9), and treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire [DTSQ]). Repeated-measures ANOVA models were used to estimate change in HRQL outcomes by treatment group over 48 months adjusting for model covariates. The effects of early discontinuation of the ACCORD intensive glycemic control arm on study results were explored. RESULTS A total of 1,956 (95%) completed the self-report HRQL instrument(s) at baseline. The intensive arm had a larger decrease in SF-36 physical health component score than the standard arm (−1.6 vs. −1.1, P = 0.0345). Treatment satisfaction (DTSQ) showed larger improvement with intensive than standard (P = 0.0004). There were no differences in mean scores of the Diabetes Symptom Checklist and PHQ-9. Effects of participant transition following discontinuation of the intensive arm on HRQL were not significant. CONCLUSIONS The ACCORD trial strategy of intensive glycemic control did not lead to benefits in HRQL and was associated with modest improvement in diabetes treatment satisfaction. Thus patient acceptability was apparently not compromised with intensive and complex interventions such as those used in ACCORD.

PDB65 COMPARISON OF FOUR HEALTH STATE PREFERENCE MEASURES AMONG PATIENTS ENROLLED IN THE ACTION TO CONTROL CARDIOVASCULAR RISK IN DIABETES TRIAL

OBJECTIVE We tested the hypothesis that intensive (systolic blood pressure [SBP] <120 mmHg) rather than standard (SBP 130–139 mmHg) blood pressure (BP) control improves health-related quality of life (HRQL) in those with type 2 diabetes. RESEARCH DESIGN AND METHODS Subjects were 1,028 ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial HRQL substudy participants who completed baseline and one or more 12-, 36-, or 48-month HRQL evaluations. Multivariable linear regression assessed impact of BP treatment assignment on change in HRQL. RESULTS Over 4.0 years of follow-up, no significant differences occurred in five of six HRQL measures. Those assigned to intensive (vs. standard) BP control had statistically significant worsening of the Medical Outcomes Study 36-item short-form health survey (SF36) physical component scores (−0.8 vs. −0.2; P = 0.02), but magnitude of change was not clinically significant. Findings persisted across all prespecified subgroups. CONCLUSIONS Intensive BP control in the ACCORD trial did not have a clinically significant impact, either positive or negative, on depression or patient-reported HRQL.