Variability in HbA1c is associated with a higher risk of cardiovascular disease and microvascular complications in patients with type 2 diabetes. The present study evaluated the severity of somatic nerve dysfunction at different stages of chronic glycemic impairment, and its correlation with different cardio-metabolic parameters. The study was conducted on 223 patients with type 2 diabetes. We calculated the intrapersonal mean, standard deviation (SD), and coefficient of variation of HbA1c for each patient using all measurements obtained for 3 years prior to the study. Patients were divided into quartiles according to the SD of HbA1c, and we constructed composite scores of nerve conduction as the severity of peripheral neuropathy. Linear regression analysis was performed to evaluate the influence of independent variables on mean composite scores. Those with higher SD-HbA1c had a higher body mass index, mean and index HbA1c, triglyceride and uric acid level, urinary albumin excretion and albumin-creatinine ratio, proportion of insulin therapy, and prevalence of hypertension as the underlying diseases, but lower estimate glomerular filtration rate (eGFR). In addition, those with higher SD-HbA1c showed lower amplitudes and reduced motor nerve conduction velocity in tested nerves, and lower sensory nerve conduction velocity in the sural nerve. Furthermore, those with higher SD-HbA1c had higher composite scores of low extremities. Multiple linear regression analysis revealed that diabetes duration, SD-HbA1c, and eGFR were independently associated with mean composite scores. Based on our results, HbA1c variability plus chronic glycemic impairment is strongly associated with the severity of peripheral neuropathy in patients with type 2 diabetes. Aggressively control blood glucose to an acceptable range and avoid blood glucose fluctuations by individualized treatment to prevent further nerve damage.

Background Variability in the glycated hemoglobin (HbA1c) level is associated with a higher risk of microvascular complications in patients with type 2 diabetes. We tested the hypothesis that HbA1c variability is not only strongly associated with the presence but also the degree of severity of cardiovascular autonomic neuropathy (CAN) in patients with long diabetes durations (more than 10 years). Methods For each patient, the intrapersonal mean, standard deviation (SD), and coefficient of variation (CV) for HbA1c were calculated using all measurements obtained 3 years before the study. We constructed the composite autonomic scoring scale (CASS) as a measure of the severity of cardiovascular autonomic functions. Stepwise logistic regression and linear regression analyses were performed to evaluate the presence of CAN and the influence of independent variables on the mean CASS, respectively. Results Those with CAN had a higher mean age, a higher low-density lipoprotein cholesterol (LDL-C), HbA1c-SD, HbA1c-CV, mean HbA1c, and index HbA1c, higher prevalence of retinopathy as the underlying disease, and lower high-density lipoprotein (HDL) levels. Stepwise logistic regression showed that HbA1c-SD and retinopathy were risk factors that were independently associated with the presence of CAN. Mean HbA1c, HbA1c-CV, HbA1c-SD, and index HbA1c were positively correlated with mean CASS, and a multiple linear regression analysis revealed that HbA1c-SD was independently associated with the mean CASS. Conclusion HbA1c variability is strongly associated with not only the presence but also the degree of severity of CAN. A longitudinal study is required to confirm whether controlling blood glucose level is effective in reducing CAN progression.