322-OR: Proinflammatory Macrophage Infiltration in Sural Nerve Is Associated with Reduction of Myelinated Nerve Fiber Density but Not IENFD in Human Diabetic Subjects

Abstract

Background: The etiology of diabetic polyneuropathy (DPN) is multifactorial, and other than hyperglycemia, circulatory disturbance such as hypertension can be involved. Pro-inflammatory macrophages (M1) infiltration in the peripheral nerve is known to be the pathogenesis of DPN. However, it is still unclear how the inflammation and circulatory disturbance are involved in the pathological changes of human DPN. Methods: Autopsied cases at Hirosaki University Hospital were evaluated: 7 nondiabetic cases (nDM), 11 nondiabetic cases with hypertension (nDM+HT), 6 diabetes cases (DM), 9 cases with hypertension and diabetes (DM+HT). Intraepidermal nerve fiber density (IENFD) was examined by immunofluorescent staining with the skin tissue 10 cm above external condyle. Dissected sural nerves were pathologically examined. Macrophage infiltration into the endoneurium of sural nerves was evaluated by double immunostaining using anti-CD68 and anti-CD163 antibodies. Results: HbA1c level was significantly higher in DM and DM+HT than in nDM (p<0.01, respectively). IENFD was significantly decreased in DM compared to nDM (p<0.05) and further decreased in DM+HT (p<0.05 vs DM). The infiltration of M1 was significantly increased in DM (p<0.05). M1 infiltration was comparable between DM and DM+HT. Regression analysis showed that the M1/anti-inflammatory macrophages (M2) ratio was not significantly correlated with IENFD (r=0.3, p=0.09). Morphometric measurements of the sural nerve using semithin sections revealed that myelinated nerve fiber density (MNFD) was significantly decreased in DM compared with nDM (p<0.05). MNFD was comparable between DM and DM+HT. MNFD was inversely correlated with M1/M2 ratio (r=0.37, p<0.05). Conclusions: Our results suggest that the factors other than sural nerve inflammation, such as hypertension, are possibly more involved in the loss of IENFD in DPN. Disclosure H. Mizukami: None. S. Osonoi: None. Y. Takeuchi: None. T. Sasaki: None.