Abstract
Hyperglycemia is associated with an increased risk of microvascular complications in patients with type 2 diabetes. The aim of the present study was to investigate whether the reduction of the levels of HbA1c by tight glycemic control (GC) decreases the rate of microvascular complications and improves the neurological measures in patients with type 2 diabetes. Detailed clinical and neurological examinations including corneal confocal microscopy (CCM) were performed in 141 Japanese patients with type 2 diabetes and 60 age-matched control subjects at baseline and follow-up with GC for 4 years. Patients were stratified according to the mean HbA1c level during follow-up into good (HbA1c < 53.0 mmol/mol, mean; 47.5 mmol/mol), fair (53.0 mmol/mol ≤HbA1c < 58.5 mmol/mol, mean; 55.6 mmol/mol), and poor (HbA1c ≥ 58.5 mmol/mol, mean; 68.9 mmol/mol) GC groups with similar HbA1c levels at baseline (84.5-88.2 mmol/mol). At baseline, CCM revealed significant nerve fiber damage in all patients compared to that in controls. The interval changes in most corneal nerve fiber (CNF) parameters and neurophysiological functions were significantly related with the mean HbA1c levels during follow-up. Interestingly, the baseline HbA1c level did not impact on neurological functions at follow-up. Interval changes in neuropathy outcomes were associated with mean clinical factors during follow-up and hypoglycemic strategies. Good GC improved all nerve functions, including CNF branch density and bead, but not the length and main fiber density. Fair GC deteriorated some nerve functions. Poor GC compromised all neuropathy outcomes. Irrespective of GC levels, retinopathy increased after follow-up period, while nephropathy decreased. This study showed that tight GC was beneficial just for nephropathy among microvascular complications. Despite strict GC, the retinopathy progressed in patients with type 2 diabetes. Glucose control did not improve neurophysiological and corneal nerve measurements unless near-normoglycemia was reached.
Highlights
Hyperglycemia is associated with an increased risk of microvascular complications in patients with type 2 diabetes mellitus (T2DM)
Neurophysiological, and corneal nerve fiber (CNF) Measure Data of Controls and Patients with Type 2 Diabetes and Their Subgroups Based on Baseline HbA1c Levels
The retinopathy was presented in 21.3% of total patients and between 18.2 and 23.4% in subgroups based on Early Treatment Diabetic Retinopathy Study (ETDRS) scale [16]
Summary
Hyperglycemia is associated with an increased risk of microvascular complications in patients with type 2 diabetes mellitus (T2DM). Several large clinical trials concluded that intensive glycemic control (GC) in type 2 diabetes is associated with a reduction in microvascular complications, in particular nephropathy and vascular outcomes [1,2,3]. It has been shown that intensive GC has an equivocal efficacy for diabetic peripheral neuropathy (DPN) in T2DM [4]. The earliest nerve fibers to undergo damage and subsequent repair are small nerve fibers (SNFs) [5, 6]. The functional and morphological measures for SNF neuropathy are essential for estimating the efficacy of intervention for DPN. It has proven to be useful as a diagnostic marker for the detection of diabetic neuropathy [9,10,11] and a range of other peripheral neuropathies [12,13,14]
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