Abstract
Normal-high HbA1c levels are a risk factor for attenuated pain sensation in normoglycemic subjects. It is unclear, however, what mechanisms underlie the pathogenesis of attenuated pain sensation in such a population. We, therefore, explored the relationship between oxidative stress (OS) and pain sensation in a rural Japanese population. A population-based study of 894 individuals (average age 53.8 ± 0.5 years) and 55 subjects with impaired fasting glucose (IFG) were enrolled in this study. Individuals with diabetes were excluded. Relationships between pain threshold induced by intraepidermal electrical stimulation (PINT) and clinico-hematological parameters associated with OS were evaluated. Univariate linear regression analyses revealed age, BMI, HbA1c, the OS biomarker urine 8-hydroxy-2′-deoxyguanosine (8-OHdG), systolic blood pressure, and decreased Achilles tendon reflex on the PINT scores. Adjustments for age, gender, and multiple clinical measures confirmed a positive correlation between PINT scores and urine 8-OHdG (β = 0.09, p < 0.01). Urine 8-OHdG correlated positively with higher HbA1c levels and age in the normoglycemic population. Unlike in the normoglycemic population, both inflammation and OS were correlated with elevated PINT scores in IFG subjects. OS may be a major contributing factor to elevated PINT scores in a healthy Japanese population.
Highlights
Overproduction of reactive oxygen species (ROS) in conjunction with the deterioration of antioxidant defenses causes an increased burden of oxidative stress (OS), leading to damages to membrane lipids, proteins, and DNA [1]
We evaluated the correlation of elevated pain threshold induced by intraepidermal electrical stimulation (PINT) scores with clinico-hematological factors relating to diabetic polyneuropathy (DPN), including OS and inflammation, in a rural Japanese population
894 normoglycemic subjects (352 men, 542 women) aged 53.8 ± 0.5 years were evaluated among 1073 volunteers (n = 1073) of the 2017 Iwaki study
Summary
Overproduction of reactive oxygen species (ROS) in conjunction with the deterioration of antioxidant defenses causes an increased burden of oxidative stress (OS), leading to damages to membrane lipids, proteins, and DNA [1]. In DPN, ROS production in the peripheral nerves is induced by multiple mechanisms [3,4] Intrinsic factors, such as excess glucose and high fatty-acid flux, can markedly increase ROS and disrupt oxidative phosphorylation in the mitochondria. This process is hypothesized to be mediated by many complex mechanisms, including increased flux through the polyol pathway and the hexosamine biosynthetic pathway, protein kinase C (PKC) activation, and increased production of advanced glycation end products (AGEs). We previously reported that the pathological factors for DPN were correlated differently with the elevation of PINT scores, depending on the stage of diabetes [21]. We explored factors responsible for eliciting OS in the same population
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