Decreased prevalence of lymphatic filariasis among diabetic subjects associated with a diminished pro-inflammatory cytokine response (CURES 83)

Abstract

Epidemiological studies have shown an inverse correlation between the incidence of lymphatic filariasis (LF) and the incidence of allergies and autoimmunity. However, the interrelationship between LF and type-2 diabetes is not known and hence, a cross sectional study to assess the baseline prevalence and the correlates of sero-positivity of LF among diabetic subjects was carried out (n = 1416) as part of the CURES study. There was a significant decrease in the prevalence of LF among diabetic subjects (both newly diagnosed [5.7%] and those under treatment [4.3%]) compared to pre-diabetic subjects [9.1%] (p = 0.0095) and non-diabetic subjects [10.4%] (p = 0.0463). A significant decrease in filarial antigen load (p = 0.04) was also seen among diabetic subjects. Serum cytokine levels of the pro-inflammatory cytokines-IL-6 and GM-CSF-were significantly lower in diabetic subjects who were LF positive, compared to those who were LF negative. There were, however, no significant differences in the levels of anti-inflammatory cytokines-IL-10, IL-13 and TGF-beta-between the two groups. Although a direct causal link has yet to be shown, there appears to be a striking inverse relationship between the prevalence of LF and diabetes, which is reflected by a diminished pro-inflammatory cytokine response in Asian Indians with diabetes and concomitant LF.

Figure 1. Reduced prevalence of Lymphatic Filariasis (LF) among diabetic individuals.

Prevalence of filarial infection in diabetic (DM-ND-Newly diagnosed and KDM-Known diabetic) and non-diabetic (NGT-Normal glucose tolerance and IGT-Impaired glucose tolerance) subjects was estimated (Panel a). The percentage of LF positive individuals in each group is shown. Statistical difference in the prevalence was determined by chi-square analysis. Filarial antigen levels in diabetic (DM-ND-Newly diagnosed and KDM-Known diabetic) and non-diabetic (NGT-Normal glucose tolerance and IGT-Impaired glucose tolerance) subjects with active filarial infection (Panel b). Statistical differences in the antigenic load were determined by Mann-Whitney U test.

Figure 2. Anti-filarial antibody levels in diabetic (DM-ND-Newly diagnosed and KDM-Known diabetic) and non-diabetic (NGT-Normal glucose tolerance and IGT-Impaired glucose tolerance) subjects with active filarial infection.

Box and whisker plots of the log transformed levels of IgG (Panel a) and IgG4 (Panel b) are shown for each of the four groups. NS = Not significant. Statistical differences in the antibody titer were determined by Mann-Whitney U test.

Figure 3. Pro- and anti - inflammatory serum cytokine levels in control (DM⁻LF⁻), diabetes alone (DM⁺LF⁻) and diabetes and LF (DM⁺LF⁺) subjects.

Serum levels of TNF-α (Panel a), IL-6 (Panel b), GM-CSF (Panel c), IFN-γ (Panel d), IL-13 (Panel e), TGF-β (Panel f) and IL-10 (Panel g) are shown. Each dot represents an individual patient, with the geometric mean represented by the horizontal bars. p values were calculated by multinomial logistic regression analysis.