Effect of a lifestyle intervention on change in cardiorespiratory fitness in adults with type 2 diabetes: results from the Look AHEAD Study.

OBJECTIVE: To examine the effect of an intensive lifestyle weight loss intervention (ILI) compared to diabetes support and education (DSE) on changes in fitness and physical activity in the Look AHEAD trial. DESIGN: Randomized clinical trial to compare a lifestyle intervention for weight loss with a DSE condition in individuals with type 2 diabetes. SUBJECTS: Data from 4376 overweight or obese adults with type 2 diabetes (age=58.7+/-6.8 years, body mass index (BMI)=35.8+/-5.8 kg/m(2)) who completed 1 year of the Look AHEAD trial and had available fitness data were analyzed. INTERVENTION: Subjects were randomly assigned to DSE or ILI. DSE received standard care plus three education sessions over the 1-year period. ILI included individual and group contact throughout the year, restriction in energy intake and 175 min per week of prescribed physical activity. MEASUREMENTS: Fitness was assessed using a submaximal graded exercise test. Physical activity was assessed by questionnaire in a subset of 2221 subjects. RESULTS: Change in fitness was statistically greater in ILI vs DSE after adjustment for baseline fitness (20.9 vs 5.7%; P<0.0001). Multivariate analysis showed that change in fitness was greater in overweight vs obese Class II and III (P<0.05). Physical activity increased by 892+/-1694 kcal per week in ILI vs 108+/-1254 kcal per week in DSE (P<0.01). Changes in fitness (r=0.41) and physical activity (r=0.42) were significantly correlated with weight loss (P<0.0001). CONCLUSIONS: The ILI was effective in increasing physical activity and improving cardiorespiratory fitness in overweight and obese individuals with type 2 diabetes. This effect may add to weight loss in improving metabolic control in patients in lifestyle intervention programs.

Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study.

OBJECTIVES: To determine whether menopausal hormone therapy (HT) affects regional brain volumes, including hippocampal and frontal regions. METHODS: Brain MRI scans were obtained in a subset of 1,403 women aged 71-89 years who participated in the Women's Health Initiative Memory Study (WHIMS). WHIMS was an ancillary study to the Women's Health Initiative, which consisted of two randomized, placebo-controlled trials: 0.625 mg conjugated equine estrogens (CEE) with or without 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet. Scans were performed, on average, 3.0 years post-trial for the CEE + MPA trial and 1.4 years post-trial for the CEE-Alone trial; average on-trial follow-up intervals were 4.0 years for CEE + MPA and 5.6 years for CEE-Alone. Total brain, ventricular, hippocampal, and frontal lobe volumes, adjusted for age, clinic site, estimated intracranial volume, and dementia risk factors, were the main outcome variables. RESULTS: Compared with placebo, covariate-adjusted mean frontal lobe volume was 2.37 cm(3) lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm(3)) lower (p = 0.05), and differences in total brain volume approached significance (p = 0.07). Results were similar for CEE + MPA and CEE-Alone. HT-associated reductions in hippocampal volumes were greatest in women with the lowest baseline Modified Mini-Mental State Examination scores (scores <90). CONCLUSIONS: Conjugated equine estrogens with or without MPA are associated with greater brain atrophy among women aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy.

Consent for genetics studies among clinical trial participants: findings from Action for Health in Diabetes (Look AHEAD).

BACKGROUND: Increasingly, genetic specimens are collected to expand the value of clinical trials through study of genetic effects on disease incidence, progression or response to interventions. PURPOSE: and methods We describe the experience obtaining IRB-approved DNA consent forms across the 19 institutions in the Action for Health in Diabetes (Look AHEAD), a clinical trial examining the effect of a lifestyle intervention for weight loss on the risk of serious cardiovascular events among individuals with type 2 diabetes. We document the rates participants provided consent for DNA research, identify participant characteristics associated with consent, and discuss implications for genetics research. RESULTS: IRB approval to participate was obtained from 17 of 19 institutions. The overall rate of consent was 89.6% among the 15 institutions that had completed consenting at the time of our analysis, which was higher than reported for other types of cohort studies. Consent rates were associated with factors expected to be associated with weight loss and cardiovascular disease and to affect the distribution of candidate genes. Non-consent occurred more frequently among participants grouped as African-American, Hispanic, female, more highly educated or not dyslipidemic. LIMITATIONS: The generalizabilty of results is limited by the inclusion/exclusion criteria of the trial. CONCLUSIONS: Barriers to obtaining consent to participate in genetic studies may differ from other recruitment settings. Because of the potentially complex associations between personal characteristics related to adherence, outcomes and gene distributions, differential rates of consent may introduce biases in estimates of genetic relationships.