Normalized HbA1c Levels Facilitate Improved Neuropathy Outcomes in T2D
Previous randomized trials have not been able to establish optimal glycemic control level for improving neuropathy outcomes in T2D.
A study published in Diabetes Care showed that normalized glycated hemoglobin (HbA1c) levels facilitated improvement in neuropathy and nephropathy in type 2 diabetes (T2D) of a short duration.
The study investigated the effect of normalized HbA1c levels without severe hypoglycemia on corneal nerve fiber measures, neurophysiological function, retinopathy, and nephropathy in participants with T2D. The study population consisted of 4 cohorts: patients with T2D with extensive HbA1c control (n = 38), patients with T2D without extensive HbA1c control (n = 38), healthy control participants with normal glucose tolerance (n = 48), and participants with impaired glucose tolerance (n = 34).
Patients with extensive HbA1c control had baseline HbA1c >7.5%, a follow-up of >3 years, and annual mean HbA1c <6.0% for the last 2 years of follow-up. Neurological deficits were assessed by the modified neuropathy disability score and corneal nerve fiber data were analyzed using in vivo corneal confocal microscopy. Estimated glomerular filtration rate and urinary creatinine and albumin levels were recorded every 3 months to assess nephropathy. Participants with diabetes with or without extensive HbA1c control were followed for an average of 4.3 and 4.1 years, respectively.
Comparative analysis of demographic data between participants with T2D with and without extensive HbA1c control showed a decrease in body mass index during follow-up in those with extensive HbA1c control. There was a significant decrease in systolic and diastolic blood pressure exhibited in the 2 study cohorts following glycemic control. Mean HbA1c levels were higher throughout follow-up in the cohort without extensive HbA1c control vs patients who had extensive HbA1c control.
The researchers reported a significant decrease in neuropathy disability score and improved results for all neurophysiological tests in the group with extensive HbA1c control. Improvements in warm perception thresholds, corneal nerve fiber density, corneal nerve fiber length, corneal nerve branch density, sural nerve sensory conduction velocity, and median nerve motor conduction velocity were closely related to mean HbA1c levels throughout follow-up. In addition, normalized HbA1c levels for 2 years were associated with decreased nephropathy and increased retinopathy.
The investigators noted the following study limitations: the lack of annual time points to assess neuropathy changes, questionable reproducibility of oral glucose tolerance test, lack of a prospective follow-up study, and concerns regarding diabetes disease duration and effective intervention strategies.
Taken together, the researchers concluded that “normalized HbA1c levels are more effective than standard care for preventing the development of neuropathy but not retinopathy” in T2D of a short duration.
Ishibashi F, Taniguchi M, Kosaka A, Uetake H, Tavakoli M. Improvement in neuropathy outcomes with normalizing HbA1c in patients with type 2 diabetes [published online November 19, 2018]. Diabetes Care. doi:10.2337/dc18-1560