Glycated hemoglobin variability, mean HbA1c and heart failure in patients with type 2 diabetes

Background: Heart failure (HF) is a common presentation in patients with type 2 diabetes mellitus (T2DM). Previous studies revealed that HbA1c level is significantly associated with HF. However, little is known about the association between HbA1c variability and HF. We aimed to evaluate the association of HbA1c variability and mean HbA1c with HF in patients with T2DM. Methods: Using Diabetes Share Care Program data, patients with T2DM had mean HbA1c (HbA1c-Mean), HbA1c variability (tertiles of HbA1c-SD and HbA1c-adjSD) within 12-24 months during 2001-2008 were included. The cutoffs of HbA1c-Mean were set at <7%, 7-7.9%, and ≥8%. Hazard ratios (HRs) for HF during 2008-2018 were estimated using Cox proportional hazards models. Results: A total of 3824 patients were included, of whom 315 patients developed HF during the 11.72 years observation period. The associated risk of HF increased with tertiles of HbA1c variability and cutoffs of HbA1c-Mean. In mutually adjusted models, HbA1c-Mean showed a consistent dose-response association with HF, while the association of HbA1c variability with HF disappeared. Among patients with HbA1c-Mean < 7%, the associated risk of HF in patients with HbA1c variability in tertile 3 was comparable to patients with HbA1c-Mean ≥8%. Conclusions: Mean HbA1c was an independent predictor of HF and not explained by HbA1c variability. In addition to absolute HbA1c level, targeting on stability of HbA1c in patients with well glycemic control was also important for the development of HF in patients with T2DM.