General Description
Short-term studies have shown numerous benefits of weight loss in overweight or obese patients, including improvements in glycemic control, risk factors for cardiovascular disease, quality of life, and other obesity-related coexisting illnesses. The Look AHEAD study was designed to test whether weight loss similarly improved cardiovascular morbidity and mortality in patients with type 2 diabetes. The study is a multicenter, randomized clinical trial that examines the long-term effects of an intensive lifestyle intervention program designed to achieve and maintain weight loss by decreased caloric intake and increased physical activity.
Eligible patients with type 2 diabetes and a body-mass index (BMI) of 25.0 or more were enrolled and randomly assigned either to participate in an intensive lifestyle intervention (intervention group) or to receive diabetes support and education (control group). The intensive lifestyle intervention, which included both group and individual counseling sessions, was aimed at achieving and maintaining weight loss of at least 7% by focusing on reduced caloric intake and increased physical activity. The diabetes support and education program featured sessions focusing on diet, exercise, and social support. Both the intervention and control programs occurred with decreasing frequency as the trial progressed. The primary outcome measure is the first occurrence of a composite cardiovascular outcome, which consists of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for angina. Participants will be followed for a planned period of 13.5 years.
An ancillary study, Look AHEAD Brain, was conducted to assess whether participation in the 10-year lifestyle intervention, as part of Look AHEAD, had an impact on white matter hyperintensity and loss of brain tissue among individuals with type 2 diabetes. A subset of Look AHEAD study participants underwent standardized brain magnetic resonance imaging in conjunction with tests assessing cognitive function 10-12 years post-randomization.
The Look AHEAD intensive lifestyle intervention ended in September, 2012. Participants continued to be followed to determine the long-term effects of the intervention on health outcomes.
The Look AHEAD Continuation Study (Look AHEAD-C) builds on the Look AHEAD study to determine the long-term impact of an intensive lifestyle intervention on 1) physical function and mobility disability, and 2) cognitive function and cognitive impairment. Collection of cognitive function measures began in Year 8 of the study and continued through Year 13.
The current data package contains data through the end of the post intervention program.
Objectives
The primary objective of the Look AHEAD study was to test whether an intensive lifestyle intervention program designed to achieve and maintain weight loss by decreased caloric intake and increased physical activity improves the long-term cardiovascular morbidity and mortality of overweight patients with type 2 diabetes.
Secondary objectives associated with the Look AHEAD Brain ancillary study were focused on understanding the impact of lifestyle interventions on brain matter among individuals with type 2 diabetes.
Objectives associated with the Look AHEAD-C study included understanding the impact of lifestyle interventions on physical and cognitive function among individuals with type 2 diabetes.
Outcome Measure
The primary outcome measure is the first occurrence of a composite cardiovascular outcome, which consists of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke, and hospitalization for angina. Participants will be followed for a planned period of 13.5 years.
There are three composite secondary outcome measures, which include: (1) death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; (2) death from any cause, myocardial infarction, stroke, or hospitalization for angina; and (3) death from any cause, myocardial infarction, stroke, hospitalization for angina, coronary-artery bypass grafting, percutaneous coronary intervention, hospitalization for heart failure, or peripheral vascular disease.
Key additional outcomes include cognitive and physical function, metabolic biomarkers, medication usage, healthcare utilization, and brain structure volumes.
Criteria
Participants between 45 and 75 years of age who met the following criteria were eligible for the study:
- Self-reported type 2 diabetes, as verified by the use of glucose-lowering medication, a physician's report, or glucose levels
- A body-mass index ≥ 25.0 ( ≥ 27.0 in patients taking insulin)
- A glycated hemoglobin level ≤ 11%
- A systolic blood pressure < 160 mm Hg; a diastolic blood pressure < 100 mm Hg
- A triglyceride level < 600 mg/deciliter
- The ability to complete a valid maximal exercise test, suggesting it was safe to exercise
- An established relationship with a primary care provider
Exclusion criteria are documented in the study protocol.
Outcome
Initial results showed that the intensive lifestyle intervention, as compared with diabetes support and education, did not reduce the risk of cardiovascular morbidity and mortality among overweight or obese patients with type 2 diabetes. While no significant differences in the primary outcome were found between the two groups, patients in the intervention group did show clinically meaningful improvements in glycated hemoglobin levels, which were greatest during the first year but were at least partly sustained throughout follow-up. This positive effect may explain why patients in the intervention group were less likely to be treated with insulin during this period. Furthermore, patients in the intervention group were more likely to have a partial remission of diabetes during the first 4 years of the trial than were those in the control group. Participants continue to be followed to determine the long-term effects of the intervention on a variety of health outcomes.
Look AHEAD Brain ancillary study found that both the total brain and hippocampus volumes were similar between intervention groups. Over the course of follow-up, it was determined that assignment to lifestyle intervention had no significant impact on cognitive function compared to the non-lifestyle intervention group. There were significant differences found in both the mean white matter hyperintensity volume and mean ventricle volume in which the lifestyle intervention group resulted in lower volumes in both.
Look AHEAD-C study found that a lifestyle intervention for overweight adults with type 2 diabetes was not associated with cognitive benefit or a lower risk of cognitive impairment when compared to a non-lifestyle intervention.
