Type 2 diabetes mellitus (T2D) 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 (HRQL). 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. The Look AHEAD: Action for Health in Diabetes (Look AHEAD) randomized controlled clinical trial (RCT) was designed to assess whether a multi-domain intensive lifestyle intervention (ILI) targeting weight loss (including counseling on caloric restriction, increased physical activity, and improved diet and metabolic risk factor monitoring) versus a control condition (diabetes support and education, DSE) would reduce risks for major cardiovascular disease (CVD) events, and subsequently many other aging-related outcomes. The intervention successfully induced and maintained long-term weight loss and benefits for many age-related health conditions (e.g., chronic kidney disease, depression, mobility, frailty indices, disability-free life years).

While lifestyle interventions are often recommended for adults with T2D and overweight/obesity, whether they meaningfully 1) prevent or mitigate multimorbidity, geriatric syndromes, and physical and cognitive declines, 2) decrease health care utilization and spending, and 3) improve the lives of older adults over an extended follow-up is unknown. A hallmark of aging is the accumulation of age-related chronic diseases or multimorbidity, which is also associated with geriatric syndromes, physical and cognitive function declines, increased health care costs, and poorer HRQL. Weight loss, however, is a marker for impending increases in multimorbidity. While intentional weight loss may ameliorate adverse consequences, unintentional (and for some outcomes, intentional) weight loss is associated with increases in multimorbidity, frailty, dementia, lean mass and bone loss, and fractures. While the Look AHEAD ILI continues a legacy of relative weight losses through subsequent follow-up, many of the health benefits related to ILI have faded and their later life trajectories are uncertain.

Continued follow-up of the Look AHEAD cohort provides an unprecedented opportunity to assess the long-term benefits and potential harms of an ILI that successfully nurtured long-term changes in behavior and improved control of risk factors. Look AHEAD has been gradually repositioned to be a platform for discovery on how behavior and clinical factors modulate aging trajectories in T2D and obesity. The Look AHEAD Aging study focused on aging and sustains a platform for age-related ancillary studies.

The primary objectives of the Look AHEAD Aging study were to identify the long-term effects of a multi-domain intensive lifestyle intervention (ILI) compared to a diabetes support and education control group (DSE) on multimorbidity and geriatric syndromes, physical function, cognitive function, health care utilization and costs, and health-related quality of life.

The secondary objectives of the Look AHEAD Aging study were to evaluate the heterogeneity of outcomes based on associations with nearly two decades of longitudinal trajectories in clinical measures (e.g., HbA1c, blood pressure, depressive symptoms, weight), medication use (e.g., metformin, insulin, statins), and behaviors (e.g., physical activity, weight control practices). Additional secondary objectives were to baseline subgroups including sex, race/ethnicity, age, obesity, and health status; and to maintain the Look AHEAD cohort as a source of discovery by promoting ancillary studies, dissemination, and distribution of well-documented public use data, and through scientific interest groups.

Disability was assessed using the Pepper Assessment Tool for Disability (PAT-D). Disability and severe disability were defined as self-reporting “a lot of difficulty” or “unable” to perform ≥ 1 and ≥ 3 activities, respectively, on PAT-D subscales for mobility, instrumental, and basic activities of daily living (IADLs and BADLs).

• All individuals who participated in the Look AHEAD program and who have given permission for further contact by a central unit (the Wake Forest School of Medicine)
• Adequate hearing ability to complete a telephone interview
• Adequate comprehension of the consent process based on the consent comprehension tool
• Individuals who are Spanish speaking as their first language are eligible

Participants who previously received research classifications of probable dementia in Look AHEAD are not eligible.

Over nine years of follow-up, odds of severe mobility disability were higher for ILI participants aged ≥70 years (OR [95% CI]: 1.50 [1.02-2.20]) but lower for those in ILI <70 years (0.69 [0.48-0.99]) compared to controls (interaction p = .0043). Participants with BMI ≥35 kg/m2 had higher odds of mobility disability (2.06 [1.57-2.70]), severe mobility disability (2.52 [1.79-3.56]), and IADL disability (OR [95% CI]: 2.15 [1.53-3.02]) compared to those with BMI <30 kg/m2. Conclusion: ILI was associated with greater severe mobility disability in participants ≥70. Regardless of age, those with higher BMI had increased late-life mobility and IADL disability.