The dominant infiltration of pro-inflammatory M1 macrophages (M1) compared to anti-inflammatory M2 macrophages (M2) exerts insulin resistance in peripheral tissues of type 2 diabetes (T2DM). This inflammatory reaction is also associated with the pathogenesis and development of diabetic complications including neuropathy (DPN). It is still unclarified, however, regarding macrophage infiltration in human DPN. The aim of this study is to clarify the significance of macrophage infiltration in sural nerve (SN) in subjects with T2DM. SN of autopsy cases was dissected from 2014 to 2016. Eleven cases (Male 6, Female 5) of non-T2DM (nDM) and 11 cases (Male 3, Female 8) of T2DM (T2D) were subjected to the evaluation. Double immunohistochemistry was performed in cross section of SN for CD68 (Pan-macrophage) and CD206 (M2). M1 was defined as CD68+ and CD206- and M2 was as CD206+, respectively. Epon-embedded semithin section was used for morphometrical assessment of SN fibers. In frozen SN, mRNA expression was evaluated by qPCR. Average age and BMI were comparable between 2 groups. HbA1c was significantly greater in T2D (mean±SE) (7.2±0.5%) than nDM (5.5±0.2%) (p<0.05). Pathological evaluation showed 2.4 times M1 in T2D more than that in nDM (p<0.05). On the other hand, M2 was comparable between 2 groups. Expression of iNOS for M1 in T2D was 1.8 times increased compared to that of nDM (p<0.05), whilst, that of CD163 for M2 was comparable between two groups. Correlation analysis between macrophage infiltration and clinical parameters disclosed that the M1 infiltration proportionally correlated with the value of HbA1c (p<0.05), whereas there was no correlation between M2 infiltration and HbA1c. SN fiber density inversely correlated with M1 population (p<0.05). Collectively, mild, but significant pro-inflammatory condition is associated with SN fiber loss, suggesting the pathogenic role of M1 in DPN.


H. Mizukami: None. S. Osonoi: None. K. Takahashi: None. K. Kudo: None. C. Itabashi: None. S. Yagihashi: None.

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