title: Helminth infections and type 2 diabetes: a cluster-randomized placebo controlled SUGARSPIN trial in Nangapanda, Flores, Indonesia.
abstract: BACKGROUND
  Insulin 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
  To 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.
  
  
  CONCLUSIONS
  The 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.
  
  
  BACKGROUND
  This 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.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. dicky.tahapary@ui.ac.id.|Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands. dicky.tahapary@ui.ac.id.
authors.forename: Dicky L
authors.initials: DL
authors.lastname: Tahapary
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands. k.de_ruiter@lumc.nl.
authors.forename: Karin
authors.initials: K
authors.lastname: de Ruiter
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands. i.martin@lumc.nl.|Department of Mathematics, Parahyangan Catholic University, Bandung, Indonesia. i.martin@lumc.nl.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Martin
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands. e.a.van_lieshout@lumc.nl.
authors.forename: Lisette
authors.initials: L
authors.lastname: van Lieshout
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands. b.g.a.guigas@lumc.nl.|Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands. b.g.a.guigas@lumc.nl.
authors.forename: Bruno
authors.initials: B
authors.lastname: Guigas
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. soewondops@yahoo.com.
authors.forename: Pradana
authors.initials: P
authors.lastname: Soewondo
authors.affiliation: Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. yenny_djuardi@yahoo.com.
authors.forename: Yenny
authors.initials: Y
authors.lastname: Djuardi
authors.affiliation: Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. aprilianto.eddy@gmail.com.
authors.forename: Aprilianto E
authors.initials: AE
authors.lastname: Wiria
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands. o.a.mayboroda@lumc.nl.
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Mayboroda
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands. j.j.houwing@lumc.nl.
authors.forename: Jeanine J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
authors.affiliation: Department of Mathematics, Faculty of Mathematics and Natural Science, Universitas Indonesia, Jakarta, Indonesia. htasman@sci.ui.ac.id.
authors.forename: Hengki
authors.initials: H
authors.lastname: Tasman
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands. e.sartono@lumc.nl.
authors.forename: Erliyani
authors.initials: E
authors.lastname: Sartono
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands. m.yazdanbakhsh@lumc.nl.
authors.forename: Maria
authors.initials: M
authors.lastname: Yazdanbakhsh
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands. jan.smit@radboudumc.nl.|Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands. jan.smit@radboudumc.nl.
authors.forename: Johannes W A
authors.initials: JW
authors.lastname: Smit
authors.affiliation: Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. taniawati@yahoo.com.
authors.forename: Taniawati
authors.initials: T
authors.lastname: Supali
mesh_terms: D000293:Adolescent; D000328:Adult; D015766:Albendazole / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D006373:Helminthiasis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007214:Indonesia; D007333:Insulin Resistance / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000871:Anthelmintics; D001786:Blood Glucose; D010919:Placebos; D015766:Albendazole