The role of pro-inflammatoy cytokines and autoimmune antibodies in diabetic peripheral neuropathy

Introduction – The pathogenetic vision of diabetes mellitus has changed in the last few years, with inflammatory and autoimmunity pathways playing roles in the development and progression of diabetic complications. This study was conducted to investigate whether inflammation and/or autoimmunity are associated with the pathogenesis of human diabetic peripheral neuropathy. Methods – A cross-sectional analysis was initially conducted to explore the population of patients with diabetes mellitus in the Kingdom of Bahrain. The demographics of patients diagnosed with diabetes mellitus in the Royal Medical Services-Bahrain Defence Force Hospital were randomly collected from 500 record cards. Case-control analysis included three groups: 30 patients with diabetic peripheral neuropathy, 30 patients with diabetes mellitus without neuropathy, and 30 healthy controls. Blood analysis was conducted to compare the levels of pro-inflammatory markers and autoimmune markers between the three groups. Secondary analysis investigated the correlations between the level of markers and sample demographics and neurological manifestations. Due to the limited time and financial resources available, this research was considered as a pilot/exploratory study encouraging further investigations to take place in the near future. Results – From the 500 sample initially selected, 48% were male (n=242) and 52% (n= 258) were female. The mean age was 55 ± 14 years and the mean BMI was 35 ± 9 kg/m². Type I DM was present in 8% (n=38) only as opposed to 92% (n=462) who had type II DM. From the sample randomly selected, 76% of the patients had other medical complications, the commonest being peripheral neuropathy; 26% (n=186) followed by vascular insufficiency; 20% (n=141). Case control analysis demonstrated very highly significant differences between the three groups in the levels of IL-6, IL-8 and IL-1β (p<0.001), highly significant differences in the levels of TNF-α, IFN-ɤ (p<0.01), and a significant difference in the levels of CRP (p<0.05). Highly significant differences between the percentages of positive and negative autoimmune antibodies (ANA) between the three groups were observed. The odds of positive values of ANAs in the neuropathy group were 50 times higher when compared to control groups. Secondary analysis detected a number of significant relationships between the levels of pro-inflammatory markers and sample demographics. Highly significant correlations were found to be associated with neurological characteristics in the neuropathy group at the levels of CRP, IL-8, and IL-1β. Conclusion – The present study demonstrated that human peripheral diabetic neuropathy is associated with increased biochemical markers of inflammation and autoimmunity. Furthermore, painful neuropathy may be associated with further increase in inflammation. These results indicate that inflammation and autoimmunity may be important contributors in the development of peripheral neuropathy in diabetes mellitus. The new pathogenic factors may lead to the consideration of new management plans involving new therapeutic approaches and disease markers.