Haemoglobin A1c variability is independently associated with carotid intima media thickness and plaque in type 2 diabetes: a retrospective, cross-sectional study

Haemoglobin A1c (HbA1c) variability, a metric reflecting long-term glycaemic fluctuation, is associated with macrovascular events in type 2 diabetes. We aimed to investigate the impacts of HbA1c variability on preclinical atherosclerosis in patients without prior cardiovascular disease. We conducted a cross-sectional study on 564 participants with diabetes who underwent general health checkups from 2016-2022. At least three HbA1c measurements were conducted for each patient. Carotid intima-media thickness (CIMT) and plaque were evaluated by B-mode ultrasonography on bilateral carotid common arteries. The standard deviation (SD) and coefficient of variance (CV) of HbA1c were calculated. We found that each doubling in CV-HbA1c and SD-HbA1c was associated with a significant increment in CIMT. The effects were more pronounced in the groups with higher mean-HbA1c (mean-HbA1c ≥6.5%). The odds ratio (95% confidence interval) for the carotid plaque was 2.68 (1.57, 4.56) and 2.88 (1.16, 5.13) in the third tertile of CV-HbA1c and SD-HbA1c respectively after fully adjusting for all the conventional risk factors in the multivariable logistic regression analysis. High mean-HbA1c plus the third tertile of HbA1c variability sharply increased the prevalence of carotid plaques. In conclusion, HbA1c variability was independently associated with CIMT and plaques in populations with diabetes. CV-HbA1c and SD-HbA1c had more effects on subclinical atherosclerosis in patients with poorly-controlled blood glucose levels.