Association between glucose variation and lower extremity amputation incidence in individuals with type 2 diabetes: a nationwide retrospective cohort study

Aims/hypothesis Elevated glucose level is one of the risk factors for lower extremity amputation (LEA), but whether glycaemic variability confers independent risks of LEA remains to be elucidated. This study aimed to investigate the association between visit-to-visit glycaemic variability and minor and major LEA risks during 8 years of follow-up in type 2 diabetic individuals aged 50 years and older. Methods This retrospective cohort study included 27,574 ethnic Chinese type 2 diabetic individuals aged >= 50 years from the National Diabetes Care Management Program in Taiwan. Glycaemic variability measures were presented as the CVs of fasting plasma glucose (FPG-CV) and of HbA(1c) (A(1c)-CV). The effect of glycaemic variability on the incidence of LEA events was analysed using Cox proportional hazards models. Results After a median follow-up of 8.9 years, 541 incident cases of LEA with a crude incidence density rate of 2.4 per 1000 person-years were observed. After multivariate adjustment, FPG-CV and A(1c)-CV were found to be significantly associated with minor LEA, with corresponding HRs of 1.53 (95% CI 1.15, 2.04) and 1.34 (95% CI 1.02, 1.77) for the third tertiles of FPG-CV and A(1c)-CV, respectively. In addition, these associations were stronger amongst older adults with longer diabetes duration (>= 3 years) than amongst those with shorter duration (<3 years) (p(interaction) < 0.01). Conclusions/interpretation Our study suggests that visit-to-visit variations in HbA(1c) and FPG are important predictors of minor LEA amongst older adults with type 2 diabetes, particularly for those with more than 3 years of diabetes duration.