Type 2 diabetes mellitus is common among older individuals in the United States, with 26.7 million cases
projected by 2050, an almost 4.5-fold increase from 2005, and the vast majority of these individuals have
overweight or obesity. Type 2 diabetes and overweight/obesity are often described as accelerators of biological
aging due to associations with decreased lifespan, increased disability risk, and reduced health-related quality
of life. Yet, not all individuals with these conditions face the same prognosis in later life, and some continue to
maintain relatively high levels of function and independence. This suggests that strategies could be identified
to promote healthier later-life experiences. It is natural to consider that behavioral intervention to promote and
maintain weight loss may mitigate against the consequences of aging.
We propose to conduct the Look AHEAD Extension-2 (LA-E2) in response to RFA-AG-21-028 Limited
Competition for the Continuation of the Look AHEAD Study, which emphasizes “assessing important health-
related outcomes over time” in a cohort that has been extensively characterized over 18 years, with an
emphasis on “outcomes that are relevant to healthy aging and resilience; major health events; healthcare
utilization; and relevant behavioral and other factors that predict, mediate, or otherwise inform the long-term
health effects of a multi-domain lifestyle intervention designed to produce and maintain weight loss in aging
adults with type 2 diabetes mellitus.” We plan to enroll approximately 2600 Look AHEAD participants who had
been randomly assigned to 10 years of either Intensive Lifestyle Intervention that successfully induced and
maintained weight loss or a comparator condition of Diabetes Support and Education. These individuals will be
followed for 4 additional years, using telephone interviews and Medicare linkage, to assess the legacy of this
intervention on important later-life outcomes.
The RFA targets five domains of outcomes: 1) Multimorbidity, 2) Physical function, 3) Cognitive function, 4)
Health care utilization and costs, and 5) Health related quality of life and health status. These goals and
outcomes frame our primary aims. We also have important secondary aims, as specified in the RFA, “to study
the heterogeneity of diabetes and chronic disease development in this well-characterized, diverse study
population.” We will describe how later-life outcomes are associated with clinical measures, medication use,
and behaviors and how intervention effects vary among individuals depending on their gender, race/ethnicity,
age, obesity, and health status. We will also maintain the Look AHEAD cohort as a source of discovery by
promoting ancillary studies, dissemination, and the distribution of well-documented public use data, and
through scientific interest groups.
Our overarching goal is to provide information that is vital for improving the care of older individuals with type
2 diabetes mellitus and overweight or obesity.