Design paper
Look 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

https://doi.org/10.1016/S0197-2456(03)00064-3Get rights and content

Abstract

Overweight and obesity are major contributors to both type 2 diabetes and cardiovascular disease (CVD). Moreover, individuals with type 2 diabetes who are overweight or obese are at particularly high risk for CVD morbidity and mortality. Although short-term weight loss has been shown to ameliorate obesity-related metabolic abnormalities and CVD risk factors, the long-term consequences of intentional weight loss in overweight or obese individuals with type 2 diabetes have not been adequately examined. The primary objective of the Look AHEAD clinical trial is to assess the long-term effects (up to 11.5 years) of an intensive weight loss program delivered over 4 years in overweight and obese individuals with type 2 diabetes. Approximately 5000 male and female participants who have type 2 diabetes, are 45–74 years of age, and have a body mass index ⩾25 kg/m2 will be randomized to one of the two groups. The intensive lifestyle intervention is designed to achieve and maintain weight loss through decreased caloric intake and increased physical activity. This program is compared to a control condition given diabetes support and education. The primary study outcome is time to incidence of a major CVD event. The study is designed to provide a 0.90 probability of detecting an 18% difference in major CVD event rates between the two groups. Other outcomes include components of CVD risk, cost and cost-effectiveness, diabetes control and complications, hospitalizations, intervention processes, and quality of life.

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

References (39)

  • Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, Phase II

    Arch Intern Med

    (1997)
  • K.F. Eriksson et al.

    Prevention of type 2 (non-insulin-dependent) diabetes mellitus by diet and physical exercise. The 6-year Malmo feasibility study

    Diabetologia

    (1991)
  • M. Higgins et al.

    Benefits and adverse effects of weight loss: observations from the Framingham Study

    Ann Intern Med

    (1993)
  • E.R. Pamuk et al.

    Weight loss and subsequent death in a cohort of US adults

    Ann Intern Med

    (1993)
  • R. Andres et al.

    Long-term effects of change in body weight on all-cause mortality: a review

    Ann Intern Med

    (1993)
  • S.N. Blair et al.

    Body weight change, all-cause mortality, and cause-specific mortality in the Multiple Risk Factor Intervention Trial

    Ann Intern Med

    (1993)
  • D.F. Williamson

    Weight loss and mortality in persons with type-2 diabetes mellitus: a review of the epidemiological evidence

    Exp Clin Endocrinol Diabetes

    (1998)
  • B.A. Franklin

    ACSM's guidelines for exercise testing and prescription

    (2000)
  • R.W. Pascale et al.

    Effects of a behavioral weight loss program stressing calorie restriction versus calorie plus fat restriction in obese individuals with NIDDM or a family history of diabetes

    Diabetes Care

    (1995)
  • Cited by (628)

    • Lifestyle-Based Obesity Care

      2023, Gastroenterology Clinics of North America
    View all citing articles on Scopus
    View full text