Visit-to-Visit HbA1c Variability Is Associated With Cardiovascular Disease and Microvascular Complications in Patients With Newly Diagnosed Type 2 Diabetes

OBJECTIVE To investigate the association between visit-to-visit HbA1c variability and cardiovascular events and microvascular complications in patients with newly diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS This retrospective cohort study analyzed patients from Tayside and Fife in the Scottish Care Information–Diabetes Collaboration (SCI-DC) who were observable from the diagnosis of diabetes and had at least five HbA1c measurements before the outcomes were evaluated. We used the previously reported HbA1c variability score (HVS), calculated as the percentage of the number of changes in HbA1c >0.5% (5.5 mmol/mol) among all HbA1c measurements within an individual. The association between HVS and 10 outcomes was assessed using Cox proportional hazards models. RESULTS We included 13,111–19,883 patients in the analyses of each outcome. The patients with HVS >60% were associated with elevated risks of all outcomes compared with the lowest quintile (for example, HVS >80 to ≤100 vs. HVS ≥0 to ≤20, hazard ratio 2.38 [95% CI 1.61–3.53] for major adverse cardiovascular events, 2.4 [1.72–3.33] for all-cause mortality, 2.4 [1.13–5.11] for atherosclerotic cardiovascular death, 2.63 [1.81–3.84] for coronary artery disease, 2.04 [1.12–3.73] for ischemic stroke, 3.23 [1.76–5.93] for heart failure, 7.4 [3.84–14.27] for diabetic retinopathy, 3.07 [2.23–4.22] for diabetic peripheral neuropathy, 5.24 [2.61–10.49] for diabetic foot ulcer, and 3.49 [2.47–4.95] for new-onset chronic kidney disease). Four sensitivity analyses, including adjustment for time-weighted average HbA1c, confirmed the robustness of the results. CONCLUSIONS Our study shows that higher HbA1c variability is associated with increased risks of all-cause mortality, cardiovascular events, and microvascular complications of diabetes independently of high HbA1c.