Visit-to-visit HbA1c variability is associated with cardiovascular disease and microvascular complications in patients with newly diagnosed type 2 diabetes

Sheyu Li, Imola Nemeth, Louise Donnelly, Simona Hapca, Kaixin Zhou, Ewan Pearson (Lead / Corresponding author)

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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 (SCIDC), who were observable from the diagnosis of diabetes and had at least five HbA1c measurements before the outcomes being evaluated. We used the previously reported HbA1c variability score (HVS) calculated as the percentage of the number of changes in HbA1c over 0.5% (5.5 mmol/mol) among all HbA1c measurement within an individual. The association between HVS and ten outcomes was assessed using Cox proportional-hazards models.

Results: We included 13,111 to 19,883 patients in the analyses of each outcome. The patients with HVS over 60% were associated with elevated risks of all outcomes compared with the lowest quintile (for example, hazard ratios and 95% confidence intervals [HVS >80 to ≤100 vs. HVS ≥0 to ≤20]: 2.38 [1.61~3.53] for major adverse cardiovascular events [MACE]; 2.4 [1.72~3.33] for all-cause mortality; 2.4 [1.13~5.11] for atherosclerotic cardiovascular [ASCV] 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; 3.49 [2.47~4.95] for the newonset chronic kidney disease). Four sensitivity analyses, including adjustment for timeweighted 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 complication of diabetes independently of high HbA1c.
Original languageEnglish
Pages (from-to)426-432
Number of pages7
JournalDiabetes Care
Issue number11
Early online date14 Nov 2019
Publication statusPublished - 20 Jan 2020



  • HbA1c variability
  • cardiovascular event
  • all-cause mortality
  • heart failure
  • diabetic retinopathy
  • diabetic peripheral neuropathy
  • diabetic foot ulcer
  • chronic kidney disease

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