Gene alterations in TERT promoter, TP53, CTNNB1, and HBV integration were closely associated with HCC development, and mutations in TERT promoter are related to poor prognosis. These results are useful for understanding the underlying mechanism of hepatocarcinogenesis, diagnosis, and predicting outcomes of patients with HCC.

Aims/IntroductionTo measure the elasticity of the tibial nerve using sonoelastography, and to associate it with diabetic neuropathy severity, the cross‐sectional area of the tibial nerve and neurophysiological findings in type 2 diabetic patients.Materials and MethodsThe elasticity of the tibial nerve was measured as the tibial nerve:acoustic coupler strain ratio using high‐resolution ultrasonography in 198 type 2 diabetic patients stratified into subgroups by neuropathy severity, and 29 control participants whose age and sex did not differ from the diabetic subgroups.ResultsThe elasticity of the tibial nerve in patients without neuropathy (P < 0.001) was reduced compared with controls (0.76 ± 0.023), further decreasing (0.655 ± 0.014 to 0.414 ± 0.018) after developing neuropathy. The cut‐off value of elasticity of the tibial nerve that suggested the presence of neuropathy was 0.558. The area under the curve (0.829) was greater than that for the cross‐sectional area (0.612). The cross‐sectional area of the tibial nerve in diabetic patients without neuropathy (6.11 ± 0.13 mm2) was larger than that in controls (4.84 ± 0.16 mm2), and increased relative to neuropathy severity (P < 0.0001). The elasticity of the tibial nerve was negatively associated with neuropathy severity (P < 0.0001), cross‐sectional area (P = 0.002) and 2000 Hz current perception threshold (P = 0.011), and positively associated with nerve conduction velocities (P < 0.0001).ConclusionsDetermining the elasticity of the tibial nerve in type 2 diabetic patients could reveal early biomechanical changes that were likely caused by thickened fibrous sheaths of peripheral nerves, and might be a novel tool for characterizing diabetic neuropathy.

This study aims to establish the corneal nerve fiber (CNF) morphological alterations in a large cohort of type 2 diabetic patients and to investigate the association between the bead size, a novel parameter representing composite of accumulated mitochondria, glycogen particles, and vesicles in CNF, and the neurophysiological dysfunctions of the peripheral nerves. 162 type 2 diabetic patients and 45 healthy control subjects were studied in detail with a battery of clinical and neurological examinations and corneal confocal microscopy. Compared with controls, patients had abnormal CNF parameters. In particular the patients had reduced density and length of CNF and beading frequency and increased bead size. Alterations in CNF parameters were significant even in patients without neuropathy. The HbA1c levels were tightly associated with the bead size, which was inversely related to the motor and sensory nerve conduction velocity (NCV) and to the distal latency period of the median nerve positively. The CNF density and length positively correlated with the NCV and amplitude. The hyperglycemia-induced expansion of beads in CNF might be a predictor of slow NCV in peripheral nerves in type 2 diabetic patients.

OBJECTIVETo 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. RESEARCH DESIGN AND METHODSDetailed 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. RESULTSIn 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. CONCLUSIONSNormalizing HbA 1c in type 2 diabetes of short duration improves microvascular complications including neuropathy and nephropathy more effectively than standard GC but not retinopathy.Intensive glycemic control (GC) has shown an equivocal efficacy regarding diabetic peripheral neuropathy (DPN) in type 2 diabetes (1), mainly due to nonoptimized HbA 1c levels. Randomized trials (2,3) have not been able to establish the optimum GC level for improving neuropathy outcomes in type 2 diabetes. In type 1

Aims/IntroductionTo evaluate the morphological changes of the median and posterior tibial nerve using high-resolution ultrasonography, and the corneal C fiber pathology by corneal confocal microscopy in type 2 diabetic patients.Materials and MethodsThe cross-sectional area, hypoechoic area and maximum thickness of the nerve fascicle of both nerves were measured by high-resolution ultrasonography in 200 type 2 diabetic patients, stratified by the severity of diabetic neuropathy, and in 40 age- and sex-matched controls. These parameters were associated with corneal C fiber pathology visualized by corneal confocal microscopy, neurophysiological tests and severity of diabetic neuropathy.ResultsThe cross-sectional area, hypoechoic area and maximum thickness of the nerve fascicle of both nerves in patients without diabetic neuropathy were larger than those in control subjects (P < 0.05 to P < 0.001), and further increased relative to the severity of neuropathy (P < 0.0001). All morphological changes of both nerves were negatively associated with motor and sensory nerve conduction velocity (P = 0.01 to P < 0.0001), and directly associated with 2,000-Hz current perception threshold (P = 0.009 to P < 0.001). The significant corneal C fiber pathology occurred before developing the neuropathy, and deteriorated only in patients with the most severe neuropathy. The association between the morphological changes of both nerves and corneal C fiber pathology was poor.ConclusionsThe morphological changes in peripheral nerves of type 2 diabetic patients were found before the onset of neuropathy, and were closely correlated with the severity of diabetic neuropathy, but not with corneal C fiber pathology.