Design paperLook AHEAD (Action for Health in Diabetes): design and methods for a clinical trial of weight loss for the prevention of cardiovascular disease in type 2 diabetes
Introduction
The current epidemic of type 2 diabetes in the United States is largely attributable to the increased incidence of obesity [1]. Type 2 diabetes is associated with a two- to fourfold increased risk for cardiovascular disease (CVD), and overweight or obese individuals with type 2 diabetes are at particularly high risk for CVD morbidity and mortality [2], [3], [4].
Although short-term weight loss has been demonstrated to ameliorate obesity-related metabolic abnormalities and CVD risk factors, no prospective randomized studies have examined the long-term consequences of intentional weight loss in overweight or obese populations [5]. Recently, several large randomized multicenter trials have demonstrated significant decreases in weight and increases in activity level for as long as 3 years, indicating feasibility to assess the long-term effects of interventions designed to promote and sustain weight loss [6], [7], [8], [9], [10], [11]. Although previous studies have demonstrated reduction in risk of developing type 2 diabetes or hypertension with weight loss through lifestyle change, none have demonstrated that such interventions will reduce CVD morbidity or mortality [6], [7], [8], [9]. This demonstration is an important goal, because some observational studies suggest that weight loss is associated with increased mortality [12], [13], [14], [15], [16].
Section snippets
Research goals
The primary hypothesis of Look AHEAD (Action for Health in Diabetes) is that an intensive lifestyle intervention to reduce weight and increase physical activity will reduce cardiovascular morbidity and mortality. It will compare, in overweight volunteers with type 2 diabetes, the long-term (up to 11.5 years) effects of two study conditions: an intensive lifestyle intervention designed to achieve and maintain weight loss by decreased caloric intake and increased physical activity versus a
Overview
Participants will be recruited over 2.5 years, beginning in 2001. Planned follow-up is until 2012, resulting in an average of 10.25 years of participant follow-up. The intensive intervention occurs during the first 4 years. Thereafter, participants are offered maintenance counseling and followed for study outcomes.
Eligibility criteria
Approximately 5000 volunteers with type 2 diabetes who meet inclusion and exclusion criteria summarized in Table 1 are to be recruited. Individuals ⩾75 years of age are excluded due
Discussion
Since Look AHEAD is an efficacy study designed to evaluate the health impact of interventions designed to produce and maintain weight loss, a decision was made to compare a control condition of diabetes support and education with a maximal weight loss program (rather than comparing several different approaches to weight loss). Prior research suggests that there is a dose-response relationship between the magnitude of weight loss and the observed change in cardiovascular risk factors, including
Conclusions
Look AHEAD addresses a major public health problem in the United States, cardiovascular morbidity and mortality in persons with type 2 diabetes. It is well known that obesity predisposes to diabetes and promotes CVD both in persons with and those without diabetes. This randomized clinical trial will determine whether an intensive weight loss intervention program, superimposed on standard medical management of diabetes and treatment of CVD risk factors, will reduce the incidence of CVD in type 2
Acknowledgements
This study is supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing
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