Does the Impact of Intensive Lifestyle Intervention on Cardiovascular Disease Risk Vary According to Frailty as Measured via Deficit Accumulation?

BACKGROUND: Individuals are often counseled to use behavioral weight loss strategies to reduce risk for cardiovascular disease (CVD). We examined whether any benefits for CVD risk from weight loss intervention extend uniformly to individuals across a range of underlying health states. METHODS: The time until first occurrence of a composite of fatal and nonfatal myocardial infarction and stroke, hospitalized angina, or CVD death was analyzed from 8 to 11 years of follow-up of 4,859 adults who were overweight or obese, aged 45-76 years with Type 2 diabetes. Individuals had been randomly assigned to either an intensive lifestyle intervention (ILI) or diabetes support and education (DSE). Participants were grouped by intervention assignment and a frailty index (FI) based on deficit accumulation, ordered from fewer (first tertile) to more (third tertile) deficits. RESULTS: Baseline FI scores were unrelated to intervention-induced weight losses and increased physical activity. The relative effectiveness of ILI on CVD incidence was inversely related to baseline FI in a graded fashion (p = .01), with relative benefit (hazard ratio = 0.73 [95% CI 0.55,0.98]) for individuals in the first FI tertile to no benefit (hazard ratio = 1.15 [0.94,1.42]) among those in the third FI tertile. This graded relationship was not seen for individuals ordered by age tertile (p = .52), and was stronger among participants aged 45-59 years (three-way interaction p = .04). CONCLUSIONS: In overweight/obese adults with diabetes, multidomain lifestyle interventions may be most effective in reducing CVD if administered before individuals have accrued many age-related health deficits. However, these exploratory analyses require confirmation by other studies. CLINICAL TRIAL REGISTRATION: NCT00017953.

Impact of Multidomain Lifestyle Intervention on Frailty Through the Lens of Deficit Accumulation in Adults with Type 2 Diabetes Mellitus.

BACKGROUND: Type 2 diabetes and obesity increase the accumulation of health deficits and may accelerate biological aging. Multidomain lifestyle interventions may mitigate against this. METHODS: Within a large, randomized clinical trial of intensive lifestyle intervention including caloric restriction, increased physical activity, dietary counseling, and risk factor monitoring compared with diabetes support and education, we examined the accumulation of health deficits across 8 years. We used two complementary frailty indices (FIs) based on deficit accumulation, one modeled on work in the Systolic Blood Pressure Intervention Trial and the other including additional deficits related to obesity and type 2 diabetes mellitus. Differences between intervention groups and their consistency among subgroups were assessed with re-randomization tests. RESULTS: Data from 4,859 adults (45-76 years at baseline, 59% female) were analyzed. Random assignment to intensive lifestyle intervention was associated with lower FI scores throughout follow-up as captured by areas under curves traced by longitudinal means (p ≤ .001), over which time mean (SE) differences between intervention groups averaged 5.8% (0.9%) and 5.4% (0.9%) for the two indices. At year 8, the percentage of participants classified as frail (FI > 0.21) was lower among intensive lifestyle intervention (39.8% and 54.5%) compared with diabetes support and education (42.7% and 60.9%) for both FIs (both p < .001). Intervention benefits were relatively greater for participants who were older, not obese, and without history of cardiovascular disease at baseline. CONCLUSIONS: Eight years of multidomain lifestyle intervention create a buffer against the accumulation of age-related health deficits in overweight or obese adults with type 2 diabetes.ClinicalTrials.gov Identifier: NCT00017953.