Improvement in Neuropathy Outcomes With Normalizing HbA_1c in Patients With Type 2 Diabetes.

Abstract

To investigate the impact of normalizing HbA_1c by extensive HbA_1c control (EHC) on neuropathy outcome measures (NOMs), nephropathy, and retinopathy in type 2 diabetes. Detailed clinical and neurological examinations were performed in two cohorts of 38 patients with uncontrolled type 2 diabetes (HbA_1c 9.6% [81.4 mmol/mol]) at baseline and after glycemic control (GC) with or without EHC by diet restriction and hypoglycemic agents over 4 years along with 48 control subjects with normal glucose tolerance (NGT) and 34 subjects with impaired glucose tolerance (IGT) only at baseline. EHC patients, control subjects, and subjects with IGT underwent oral glucose tolerance tests. Glycemic variability (GV) was evaluated by SD and coefficient of variation of monthly measured HbA_1c levels and casual plasma glucose. In the EHC cohort, HbA_1c levels over 4.3 years and the last 2 years improved to 6.1% (43.2 mmol/mol) and 5.8% (39.9 mmol/mol) with 7.3 kg body wt reduction, and 50% and 28.9% of patients returned to IGT and NGT, respectively, at end point. Baseline neurophysiological and corneal nerve fiber (CNF) measures were impaired in patients. Normalized HbA_1c with EHC improved neurophysiological and CNF measures to be similar for those for IGT, while GC without EHC (mean HbA_1c level 7.0% [53.5 mmol/mol]) improved only vibration perception. The mean normalized HbA_1c levels by EHC determined NOM improvements. The high GV and baseline HbA_1c levels compromised NOMs. Albumin excretion rate significantly decreased, while retinopathy severity and frequency insignificantly worsened on EHC. Normalizing HbA_1c in type 2 diabetes of short duration improves microvascular complications including neuropathy and nephropathy more effectively than standard GC but not retinopathy.