Metabolic Consequences of Concomitant Strongyloides stercoralis Infection in Patients With Type 2 Diabetes Mellitus

Abstract

Background Human and animal studies have demonstrated that helminth infections are associated with a decreased prevalence of type 2 diabetes mellitus (T2DM). However, very little is known about their biochemical and immunological interactions. Methods To assess the relationship between a soil-transmitted helminth, Strongyloides stercoralis (Ss), and T2DM, we examined analytes associated with glycemic control, metabolic processes, and T-cell–driven inflammation at the time of Ss diagnosis and 6 months after definitive anthelmintic treatment. We measured plasma levels of hemoglobin A1c, glucose, insulin, glucagon, adipocytokines, and T-helper (TH) 1-, 2-, and 17- associated cytokines in patients with T2DM with (INF group) or without (UN group) Ss infection. In INF individuals, we again assessed the levels of these analytes 6 months following anthelmintic treatment. Results Compared to UN individuals, INF individuals exhibited significantly diminished levels of insulin and glucagon that increased significantly following therapy. Similarly, INF individuals exhibited significantly diminished levels of adiponectin and adipsin that reversed following therapy. INF individuals also exhibited significantly decreased levels of the TH1- and TH17- associated cytokines in comparison to UN individuals; again, anthelmintic therapy augmented these levels. As expected, INF individuals had elevated levels of TH2-associated and regulatory cytokines that normalized following definitive therapy. Multivariate analysis revealed that these changes were independent of age, sex, body mass index, and liver and renal function. Conclusions Strongyloides stercoralis infection is associated with a significant modulation of glycemic, hormonal, and cytokine parameters in T2DM and its reversal following anthelmintic therapy. Hence, Ss infection has a protective effect on diabetes-related parameters.

Helminth infection modulates systemic pro-inflammatory cytokines and chemokines implicated in type 2 diabetes mellitus pathogenesis

“…The baseline demographic characteristics and biochemical parameters of Ss+ and Ss-individuals are shown in Table 1. As shown and as described previously [13], there were no significant differences in age, sex, BMI or other biochemical parameters between the two groups.…”

“…All the study participants were assessed as part of a natural history study protocol (12-I-073) approved by Institutional Review Boards of the National Institute of Allergy and Infectious Diseases (USA) and the National Institute for Research in Tuberculosis (India), and informed written consent was obtained from all participants. This was the same study population that was previously used for assessment of metabolic parameters [13].…”

“…The cross-talk between innate and adaptive immune cell subsets on the one hand and the metabolic cells on the other leads to a complex network governing metabolic functions both at a systemic and tissue specific level [20,21]. Interestingly, regulatory pathways induced by chronic helminth infections have been associated with reduced insulin resistance and a lower prevalence of metabolic syndrome and T2DM [4,5,7,8,13,22], suggesting that helminth-mediated immunomodulation affords a protective effect against metabolic diseases [23]. Elevated levels of pro-inflammatory cytokines have been described in both cross-sectional and prospective studies in T2DM [24][25][26].…”

“…While an inverse association has been reported between infection with Schistosoma japonicum and Ss and the prevalence of metabolic syndrome and T2DM, anthelmintic therapy was shown to impair metabolic homeostasis as characterized by increased homeostatic model assessment for insulin resistance (HOMA-IR) and haemoglobin A1c [4,13,22]. Our study again offers a plausible biological mechanism for this effect by demonstrating that anthelmintic treatment restores (at least partially) the elevated levels of pro-inflammatory cytokines and was performed to show the distribution of data from the combination of two groups Ss+ (blue circles) and Ss-(red circles)(A); and Post-T Ss+ (blue circles) and Ss-(red circles) (B).…”

The interplay of type 2 immunity, helminth infection and the microbiota in regulating metabolism

“…More importantly, they could show a significant deterioration of these parameters after anthelmintic therapies. 58 Two others studies in Indonesia and Uganda demonstrated similar outcomes after treatment against STHs and S. mansoni, respectively. 59,60 Finally, a cross-sectional analyses of several studies linking helminth infection and metabolic syndrome confirmed the trend towards a decreased prevalence of metabolic syndrome in people with past or present helminth infection.…”