Visit-to-visit HbA_1c 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 HbA_1c 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 hadatleast five HbA_1c measurements beforethe outcomes were evaluated. We used the previously reported HbA_1c variability score (HVS), calculated as the percentage of the number of changes in HbA_1c ≥0.5% (5.5 mmol/mol) among all HbA_1c 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 HbA_1c, confirmed the robustness of the results.

Conclusions: Our study shows that higher HbA _1c variability is associated with increased risks of all-cause mortality, cardiovascular events, and microvascular complications of diabetes independently of high Hb_1c.