Abstract
Purpose: Small fiber dysfunction is common in subjects with diabetic polyneuropathy (DPN). It is unsettled, however, whether marginal glucose intolerance is implicated in the onset and progression of small fiber dysfunction. Herein, we explored the relationship between glycated hemoglobin levels (HbA1c) and pain sensation in the Japanese population.Methods: A population-based study of 894 individuals (352 men, 542 women; average age 53.8 ± 0.5 years) and 55 subjects with impaired fasting glucose (IFG) in the 2017 Iwaki project were enrolled in this study. Individuals with diabetes were excluded. Relationships between pain threshold for intraepidermal electrical stimulation (P-IES) and parameters associated with metabolic syndrome were examined.Results: P-IES was elevated with increasing of age in women but not in men. Average P-IES (mA) was increased in IFG subjects (n = 55, 0.20 ± 0.03) compared with normoglycemic/non-IFG individuals (n = 894, 0.15 ± 0.01) (p < 0.01). It was comparable between IFG and a group of normal high HbA1c (5.9–6.4%). Univariate linear regression analyses showed no influence of sex, triglyceride, or cholesterol on the value of P-IES. In contrast, there were significant correlations between P-IES and serum HbA1c level (ß = 0.120, p < 0.001) Adjustments for the multiple clinical measurements confirmed positive correlation of P-IES with HbA1c (ß = 0.077, p = 0.046).Conclusion: Individuals with normal high HbA1c exhibited an elevated P-IES in a healthy Japanese population which may be useful for the screening of subclinical DPN.
Highlights
Diabetic polyneuropathy (DPN) is the most common and earliest diabetic microvascular complication [1]
We explored the possibility of normal high HbA1c levels as P-intraepidermal electrical stimulation (IES) screening indices for small fiber dysfunction
We recruited fasting normoglycemic (Control) individuals and those who impaired fasting glucose (IFG) without a history of diabetes who participated as volunteers in the Iwaki study, a health promotion study of Japanese individuals over 10 years of age
Summary
Diabetic polyneuropathy (DPN) is the most common and earliest diabetic microvascular complication [1]. DPN is a slowly progressive sensory predominant neuropathy characterized by a distal “dying back” type, in which nerve fibers are retrogradely injured from periphery [2]. In this type of neuropathy, small fibers in the distal foot are often first to be affected. Small fiber neuropathy (SFN) is the earliest form of DPN in patients with impaired glucose tolerance (IGT) who experience significant loss or dysfunction of small intraepidermal nerve fibers without large fiber defects [4]. Dysfunction or loss of small fibers is observed in preclinical asymptomatic DPN. Asymptomatic preclinical DPN is difficult to distinguish from SFN without a large fiber evaluation. There is some controversy as to whether prediabetic DPN really exists [6], new diagnostic tools such as corneal confocal microscopy confirm the reduction of small fiber density and length in IGT [7]
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