To examine the association between frailty and incident type 2 diabetes mellitus (T2DM), considering the joint effect of multimorbidity and genetic risk.

The study included 429,022 individuals in the UK Biobank. We used Cox regression with hazard ratio (HR) and 95 % confidence interval (CI) to 1) evaluate the associations of frailty with incident T2DM, 2) explore whether frailty and multimorbidity would have a joint effect, and 3) assess whether the associations were modified by genetic risk.

Compared with non-frail individuals, prefrail and frail individuals were at higher risk of T2DM: HR[95 %CI] = 1.42 [1.38;1.47] for prefrailty and 1.81[1.70;1.92] for frailty. Five frailty components were associated with increased risk of T2DM: HR[95 %CI] = 1.21[1.17;1.26] for weight loss, 1.35[1.30;1.40] for exhaustion, 1.31[1.26;1.37] for low physical activity, 1.27[1.20;1.33] for low grip strength, and 1.47[1.41;1.52] for slow gait speed. The increased risks were more pronounced among frail individuals with more than three morbidities: HR[95 %CI] = 4.10[3.76;4.46]. Frail individuals at high genetic risk had a four and a half-fold greater risk of T2DM compared with non-frail individuals at low genetic risk: HR[95 %CI] = 4.54[4.14;4.97].

Frailty was associated with increased risk of T2DM, especially in individuals with higher number of morbidities and high genetic risk. Frailty may be an independent risk factor for T2DM and targeted strategies to prevent and manage frailty would contribute to reducing the risk of T2DM.