Helminth infections and type 2 diabetes: a cluster-randomized placebo controlled SUGARSPIN trial in Nangapanda, Flores, Indonesia

Abstract

BackgroundInsulin resistance is a strong predictor of the development of type 2 diabetes mellitus. Chronic helminth infections might protect against insulin resistance via a caloric restriction state and indirectly via T-helper-2 polarization of the immune system. Therefore the elimination of helminths might remove this beneficial effect on insulin resistance.Methods/DesignTo determine whether soil-transmitted helminth infections are associated with a better whole-body insulin sensitivity and whether this protection is reversible by anthelmintic treatment, a household-based cluster-randomized, double blind, placebo-controlled trial was conducted in the area of Nangapanda on Flores Island, Indonesia, an area endemic for soil-transmitted helminth infections. The trial incorporates three monthly treatment with albendazole or matching placebo for one year, whereby each treatment round consists of three consecutive days of supervised drug intake. The presence of soil-transmitted helminths will be evaluated in faeces using microscopy and/or PCR. The primary outcome of the study will be changes in insulin resistance as assessed by HOMA-IR, while the secondary outcomes will be changes in body mass index, waist circumference, fasting blood glucose, 2 h-glucose levels after oral glucose tolerance test, HbA1c, serum lipid levels, immunological parameters, and efficacy of anthelmintic treatment.DiscussionThe study will provide data on the effect of helminth infections on insulin resistance. It will assess the relationship between helminth infection status and immune responses as well as metabolic parameters, allowing the establishment of a link between inflammation and whole-body metabolic homeostasis. In addition, it will give information on anthelmintic treatment efficacy and effectiveness.Trial registrationThis study has been approved by the ethical committee of Faculty of Medicine Universitas Indonesia (ref: 549/H2.F1/ETIK/2013), and has been filed by the ethics committee of Leiden University Medical Center, clinical trial number: ISRCTN75636394. The study is reported in accordance with the CONSORT guidelines for cluster-randomised trials.

Improved diagnosis of Trichuris trichiura by using a bead-beating procedure on ethanol preserved stool samples prior to DNA isolation and the performance of multiplex real-time PCR for intestinal parasites

“…Because of the these practical limitations of ethanol preservation, direct freezing of stool samples has been applied in a recently performed survey on Flores Island, Indonesia, studying the effect of three monthly household treatments with albendazole (Tahapary et al 2015). Based on microscopy only, the prevalence of T. trichiura was found to be 21·5% at baseline, and with a median egg count of 100 epg, intensity of infection was already low before the intervention started.…”

Cardiovascular disease and type 2 diabetes in evolutionary perspective: A critical role for helminths?

“…Golden hamsters injected with S. mansoni -derived soluble egg antigen showed reduced blood cholesterol, and atherosclerotic plaque size and progression, partly by reducing the number of inflammatory monocytes, and reducing recruitment and accumulation of myeloid cells in the plaques [121]. An ongoing clinical trial in Indonesia (SUGARSPIN) is employing randomized double-blind, placebo-controlled experiments to better test causal relationships between helminths, insulin sensitivity and metabolic variables [187]. The mouse experiment introducing the anti-inflammatory glycoprotein ES-62 secreted by a filarial nematode that inhibited inflammation and protected against arthritis, asthma, and atherosclerosis highlights another avenue of potential intervention using helminth protein products [109].…”

Type 2 responses at the interface between immunity and fat metabolism

“…Extant approaches to this goal are many and varied, but examples that have shown promise in preclinical studies (and in early clinical studies, in some cases) include the administration of helminths or helminth-derived products [51,52], which potently stimulate type 2 immunity; direct restoration of Treg populations, either by T cell ablation and repopulation or IL-2-mediated Treg promotion [53]; and restoration of healthy gut flora through either ablation and reconstitution or supplementation and competition [54], both of which are associated with promotion of systemic type 2 immune tone [55]. …”