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Background Individuals with diabetes have a high frailty burden and increased risk of heart failure (HF). In this study, we evaluated the association of baseline and longitudinal changes in frailty with risk of HF and its subtypes: HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). Methods Participants (age: 45–76 years) of the Look AHEAD trial without prevalent HF were included. The frailty index (FI) was used to assess frailty burden using a 35-variable deficit model. The association between baseline and longitudinal changes (1- and 4-year follow-up) in FI with risk of overall HF, HFpEF (ejection fraction [EF] ≥ 50%), and HFrEF (EF < 50%) independent of other risk factors and cardiorespiratory fitness was assessed using adjusted Cox models. Results The study included 5 100 participants with type 2 diabetes mellitus, of which 257 developed HF. In adjusted analysis, higher frailty burden was significantly associated with a greater risk of overall HF. Among HF subtypes, higher baseline FI was significantly associated with risk of HFpEF (hazard ratio [HR] [95% CI] per 1-SD higher FI: 1.37 [1.15–1.63]) but not HFrEF (HR [95% CI]: 1.19 [0.96–1.46]) after adjustment for potential confounders, including traditional HF risk factors. Among participants with repeat measures of FI at 1- and 4-year follow-up, an increase in frailty burden was associated with a higher risk of HFpEF (HR [95% CI] per 1-SD increase in FI at 4 years: 1.78 [1.35–2.34]) but not HFrEF after adjustment for other confounders. Conclusions Among individuals with type 2 diabetes mellitus, higher baseline frailty and worsening frailty burden over time were independently associated with higher risk of HF, particularly HFpEF after adjustment for other confounders.

Type 2 diabetes mellitus (T2DM) has been linked to accelerated biological aging and the accumulation of health deficits. It is unknown whether glycemic control can slow the progression of aging, as expressed by deficit accumulation frailty indices (FIs). We examined the cross-sectional and longitudinal associations that glycemic control, diabetes medication use, and weight change (predictors) had with a FI calculated as the percent of 36 deficits in behavioral, functional, and clinical characteristics (outcome). We drew data from 4177 participants across 8 years of follow-up in the Look AHEAD clinical trial of a multidomain intensive lifestyle intervention in individuals aged 45-76 years with T2DM and overweight or obesity. At baseline, the means(SD) FI(as a percent) for participants grouped as HbA1c< 7%, 7-7.9%, and >8% were: 19.93(6.45), 20.82(6.89), and 21.53(7.27), p< 0.001. Compared with HbA1c>8%, HbA1c< 7% at baseline was associated with 23% less mean 8-year FI progression: 2.42(7.35) vs 3.14(8.02), p< 0.001). Maintaining average HbA1c< 7% vs >8% during follow-up was associated with 47% less 8-year FI progression: 2.05(7.35) vs 3.14(8.02), p< 0.001. With adjustment for HbA1c, sustained weight loss >5% compared with weight gain >5% was associated with an 81% reduction in 8-year FI progression: 1.18(7.25) vs 3.89(8.09), p< 0.001. Use of metformin across >50% of annual visits was associated with a 30% reduction in 8-year progression of FI as compared with less use or no use: 2.25(7.27) vs 3.22(7.90), p=0.002. We conclude that better control of HbA1c, and sustained weight loss (>5%) and metformin use, may slow the accelerated aging associated with T2DM.

OBJECTIVE Patients with type 2 diabetes are encouraged to lose weight, but excessive weight loss in older adults may be a marker of poor health and subsequent mortality. We examined weight change during the postintervention period of Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) with diabetes support and education (DSE) (control) in overweight/obese individuals with type 2 diabetes and sought to identify predictors of excessive postintervention weight loss and its association with mortality. RESEARCH DESIGN AND METHODS These secondary analyses compared postintervention weight change (year 8 to final visit; median 16 years) in ILI and DSE in 3,999 Look AHEAD participants. Using empirically derived trajectory categories, we compared four subgroups: weight gainers (n = 307), weight stable (n = 1,561), steady losers (n = 1,731), and steep losers (n = 380), on postintervention mortality, demographic variables, and health status at randomization and year 8. RESULTS Postintervention weight change averaged −3.7 ± 9.5%, with greater weight loss in the DSE than the ILI group. The steep weight loss trajectory subgroup lost on average 17.7 ± 6.6%; 30% of steep losers died during postintervention follow-up versus 10–18% in other trajectories (P < 0001). The following variables distinguished steep losers from weight stable: baseline, older, longer diabetes duration, higher BMI, and greater multimorbidity; intervention, randomization to control group and less weight loss in years 1–8; and year 8, higher prevalence of frailty, multimorbidity, and depressive symptoms and lower use of weight control strategies. CONCLUSIONS Steep weight loss postintervention was associated with increased risk of mortality. Older individuals with longer duration of diabetes and multimorbidity should be monitored for excessive unintentional weight loss.