Diminished Circulating Levels of Angiogenic Factors and Rage Ligands in Helminth–Diabetes Comorbidity and Reversal Following Anthelmintic Treatment

Abstract

Background Various epidemiological and experimental studies propose that helminths could play a preventive role against the progression of Type 2 diabetes mellitus (T2DM). T2DM induces microvascular and large vessel complications mediated by elevated levels of angiogenic factors and soluble RAGE ligands. However, the interactions between helminths and host angiogenic factors and RAGE ligands are unexplored. Methods To assess the relationship between a soil-transmitted helminth, Strongyloides stercoralis (Ss) and T2DM, we measured plasma levels of VEGF-A, C, D, Angio-1 and Angio-2 and their receptors VEGF-R1, R2 and R3 as well as sRAGE and their ligands AGE, S100A12 and HMBG-1 in individuals with T2DM with Ss+ or without Ss infection (Ss-). In Ss+ individuals, we also measured the levels of aforementioned factors 6 months following anthelmintic therapy. Results Ss+ individuals exhibited significantly decreased levels of VEGF-A, C, D, Angio-1 and Angio-2 and their soluble receptors VEGF-R1, R2 and R3, that increased following anthelmintic therapy. Likewise, Ss+ individuals exhibited significantly decreased levels of AGE and their ligands sRAGE, S100A12 and HMBG-1 which reversed following anthelmintic therapy. Conclusion Our data suggest that Ss infection could play a beneficial role by limiting or delaying the T2DM related vascular complications.

Association of Strongyloides stercoralis infection and type 2 diabetes mellitus in northeastern Thailand: Impact on diabetic complication-related renal biochemical parameters

“…stercoralis infection ( Fig 3 ). These findings are contrary to previous work conducted in schistosomiasis [ 8 , 19 , 37 ], opisthorchiasis [ 47 ] and soil-transmitted helminths [ 48 ], which have all reported that infection with parasites could lead to changed serum lipid levels (LDL-C and/or HDL levels,) or BMI, which in turn helps to prevent the development of disease complications [ 21 , 49 ]. These differences might be a consequence of differing participant age groups, recently of infection, worm burdens, geographical area, culture, and dietary habits.…”

“…Recent study has indicated that infection with S . stercoralis could play a beneficial role by limiting T2DM-related vascular complications [ 21 ]. However, the mechanism underlying the relationship between helminth infection, particularly S .…”

Impact of Strongyloides stercoralis infection on complement activation in Type 2 diabetes mellitus: Insights from a clinical and anthelmintic intervention study

“…The baseline demographic characteristics and biochemical parameters have been described previously [ 5 – 8 , 13 ] and there were no significant differences in age, sex, BMI or other biochemical parameters between the 2 groups ( Table 1 ).…”

“…All recruited individuals were confirmed negative for other viral infections, as well as active and latent tuberculosis. This is the same cohort of individuals in our previously published reports [ 5 – 8 ].…”

“…We also examined the effect of anthelmintic treatment on these complement proteins and complement regulatory proteins. Emerging epidemiological and experimental studies have shown that helminth infections protect against the development and exacerbation of DM and other metabolic disorders in the host [ 5 – 8 , 14 – 17 ]. Recently, metabolic disorders with coincident helminth infections have gained attention owing to the suggestion that concomitant helminth infections may facilitate a beneficial impact on metabolic impairment [ 18 , 19 ].…”