Long-term Impact of a 10-Year Intensive Lifestyle Intervention on a Deficit Accumulation Frailty Index: Action for Health in Diabetes Trial.

BACKGROUND: Multidomain lifestyle interventions may slow aging as captured by deficit accumulation frailty indices; however, it is unknown whether benefits extend beyond intervention delivery. METHODS: We developed a deficit accumulation frailty index (FI-E) to span the 10 years that the Action for Health in Diabetes (Look AHEAD) randomized controlled clinical trial delivered interventions (a multidomain lifestyle intervention focused on caloric restriction, increased physical activity, and diet compared to a control condition) and to extend across an additional 8 years post-delivery. The study cohort included 5 145 individuals, aged 45-76 years at enrollment, who had type 2 diabetes and either obesity or overweight. RESULTS: Overall, FI-E scores were relatively lower among lifestyle participants throughout follow-up, averaging 0.0130 [95% confidence interval: 0.0104, 0.0156] (p < .001) less across the 18 years. During Years 1-8, the mean relative difference between control and lifestyle participants' FI-E scores was 0.0139 [0.0115, 0.0163], approximately 10% of the baseline level. During Years 9-18, this average difference was 0.0107 [0.0066, 0.0148]. Benefits were comparable for individuals grouped by baseline age and body mass index and sex but were not evident for those entering the trial with a history of cardiovascular disease. CONCLUSIONS: Multidomain lifestyle intervention may slow biological aging long term, as captured by an FI-E. Clinical Trials Registration Number: NCT00017953.

Rationale, design, and cohort characteristics of the Action for Health in Diabetes Aging study.

INTRODUCTION: Diabetes and overweight/obesity are described as accelerating aging processes, yet many individuals with these conditions maintain high levels of cognitive and physical function and independence late into life. The Look AHEAD Aging study is designed to identify 20-year trajectories of behaviors, risk factors, and medical history associated with resilience against geriatric syndromes and aging-related cognitive and physical functional deficits among individuals with these conditions. METHODS: Look AHEAD Aging extends follow-up of the cohort of the former 10-year Look AHEAD trial. The original cohort (N = 5145) was enrolled in 2001 to 2004 when participants were aged 45 to 76 years and randomly assigned to a multidomain intensive lifestyle intervention (ILI) or a diabetes support and education (DSE) condition. The trial interventions ceased in 2012. Clinic-based follow-up continued through 2020. In 2021, the cohort was invited to enroll in Look AHEAD Aging, an additional 4-year telephone-based follow-up (every 6 months) enhanced with Medicare linkage. Standardized protocols assess multimorbidity, physical and cognitive function, health care utilization, and health-related quality of life. RESULTS: Of the original N = 5145 Look AHEAD participants, N = 1552 active survivors agreed to participate in Look AHEAD Aging. At consent, the cohort's mean age was 76 (range 63 to 94) years and participants had been followed for a mean of 20 years. Of the original Look AHEAD enrollees, those who were younger, female, or with no history of cardiovascular disease were more likely to be represented in the Look AHEAD Aging cohort. Intervention groups were comparable with respect to age, diabetes duration, body mass index, insulin use, hypertension, cardiovascular disease, and cognitive function. ILI participants had significantly lower deficit accumulation index scores. DISCUSSION: By continuing the long-term follow-up of an extensively characterized cohort of older individuals with type 2 diabetes, Look AHEAD Aging is well positioned to identify factors associated with resilience against aging-related conditions.