Frailty and risk of microvascular disease in adults with prediabetes

Background and aims: To assess the relationship between frailty phenotypes and the risk of MVD among prediabetics in two prospective cohorts. Methods: The study included 66,068 and 226 participants with prediabetes from the UK Biobank (UKB) and Chinese Ocular Imaging Project (COIP) in Guangzhou, China, respectively. Frailty was evaluated using the Fried phenotype, which includes weight loss, fatigue, low grip strength, low physical activity, and slow walking pace. The outcome was incident microvascular diseases, including diabetic retinopathy, nephropathy, and neuropathy in UKB, and decline rate of retinal capillary density in COIP. Cox models were used to calculate hazard ratios (HRs) and 95 % confidential intervals (CIs), and mixed linear model was used to determine the beta and 95 % CIs. Results: At baseline, 27,491 (41.6 %) and 3332 (5.0 %) prediabetics were classified as pre-frail and frail, respectively in UKB. During a median follow-up of 8.9 years, 3784 cases of incident microvascular diseases were identified. Pre-frailty and frailty were significantly associated with a higher risk of microvascular diseases (HR 1.21 [1.12, 1.30] for pre-frailty; HR 1.60 [1.42, 1.81] for frailty). Compared to no frailty, the adjusted HRs for frailty were 1.42 (0.73, 2.76) for retinopathy, 1.49 (1.31, 1.70) for nephropathy, and 2.37 (1.69, 3.33) for neuropathy. Fatigue and walking pace were the strongest mediators of frailty and microvascular diseases. In the COIP, the lowest handgrip strength group exhibited 62%-63 % faster annually decline in retinal capillary density compared with the highest group (all P<0.05). Conclusions: Each frailty point is important for prediabetics because both pre-frailty and frailty phenotypes are strongly associated with an increased risk of microvascular diseases and its subtypes. Lower handgrip strength presents with faster decline in retinal capillary density.