Visit-to-visit HbA1c variability, risk of all-cause mortality and diabetes-related vascular complications among adult individuals with type 2 diabetes mellitus.

BACKGROUND: We examined the association between visit-to-visit HbA1c variability and risk of mortality, acute myocardial infarction (AMI), stroke, lower extremity amputation (LEA), neuropathy, and nephropathy. METHODS: We conducted a retrospective cohort study of adults with type 2 diabetes managed at specialist outpatient clinics between 2009 and 2017. HbA1c variability was assessed using intra-individual visit-to-visit coefficient of variation (COV), variation independent of mean (VIM), and HbA1c Variability Score (HVS). Diabetes-related outcomes were identified using diagnosis and service codes. Cox proportional hazards and weighted Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The cohort comprised 18 293 patients (mean age: 63.8 ± 13.1 years; 55.1% male). Compared to those in the lowest quartiles of HbA1c variability, patients in the highest quartile had higher HRs for mortality (COV: HR = 2.03, 95% CI: 1.43-2.88; VIM: HR = 2.70, 95% CI: 1.61-4.53; HVS: HR = 2.32, 95% CI: 1.49-3.62), and nephropathy (COV: HR = 1.34, 95% CI: 1.14-1.56; VIM: HR = 1.31, 95% CI: 1.14-1.52; HVS: HR = 1.20, 95% CI: 1.04-1.39), with statistically significant tests for linear trend. No significant associations were observed between HbA1c variability and AMI (HR = 0.88, 95% CI: 0.51-1.52), stroke (HR = 1.19, 95% CI: 0.92-1.56), neuropathy (HR = 1.01, 95% CI: 0.80-1.28), or LEA (HR = 1.00, 95% CI: 0.65-1.55). CONCLUSION: Higher HbA1c variability was associated with significantly increased risk of mortality and nephropathy, but not significantly associated with the risk of AMI, stroke, neuropathy, or LEA.