Effect of experimental hookworm infection on insulin resistance in people at risk of type 2 diabetes.
| Title: | Effect of experimental hookworm infection on insulin resistance in people at risk of type 2 diabetes. |
|---|---|
| Authors: | Pierce DR; Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.; McDonald M; Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.; Merone L; College of Health Sciences, James Cook University, Cairns, QLD, Australia.; Becker L; Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.; Thompson F; Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.; University of South Australia, Adelaide, SA, Australia.; Lewis C; College of Health Sciences, James Cook University, Cairns, QLD, Australia.; Ryan RYM; Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.; Hii SF; Melbourne Veterinary School, Faculty of Science, University of Melbourne, Parkville, VIC, Australia.; Zendejas-Heredia PA; Melbourne Veterinary School, Faculty of Science, University of Melbourne, Parkville, VIC, Australia.; Traub RJ; Melbourne Veterinary School, Faculty of Science, University of Melbourne, Parkville, VIC, Australia.; Field MA; Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.; College of Public Health, Medical & Vet Sciences, James Cook University, Cairns, QLD, Australia.; Immunogenomics Laboratory, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; Rahman T; The Department of Gastroenterology and Hepatology, The Prince Charles Hospital, Brisbane, QLD, Australia.; Croese J; Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.; Loukas A; Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.; McDermott R; Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.; University of South Australia, Adelaide, SA, Australia.; Giacomin PR; Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia. paul.giacomin@jcu.edu.au. |
| Source: | Nature communications [Nat Commun] 2023 Jul 26; Vol. 14 (1), pp. 4503. Date of Electronic Publication: 2023 Jul 26. |
| Publication Type: | Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| MeSH Terms: | Hookworm Infections*/complications ; Hookworm Infections*/drug therapy ; Hookworm Infections*/epidemiology ; Diabetes Mellitus, Type 2* ; Insulin Resistance*; Animals ; Female ; Male ; Fasting ; Necator americanus ; Humans ; Adult |
| Abstract: | The reduced prevalence of insulin resistance and type 2 diabetes in countries with endemic parasitic worm infections suggests a protective role for worms against metabolic disorders, however clinical evidence has been non-existent. This 2-year randomised, double-blinded clinical trial in Australia of hookworm infection in 40 male and female adults at risk of type 2 diabetes assessed the safety and potential metabolic benefits of treatment with either 20 (n = 14) or 40 (n = 13) Necator americanus larvae (L3) or Placebo (n = 13) (Registration ACTRN12617000818336). Primary outcome was safety defined by adverse events and completion rate. Homoeostatic model assessment of insulin resistance, fasting blood glucose and body mass were key secondary outcomes. Adverse events were more frequent in hookworm-treated participants, where 44% experienced expected gastrointestinal symptoms, but completion rates were comparable to Placebo. Fasting glucose and insulin resistance were lowered in both hookworm-treated groups at 1 year, and body mass was reduced after L3-20 treatment at 2 years. This study suggests hookworm infection is safe in people at risk of type 2 diabetes and associated with improved insulin resistance, warranting further exploration of the benefits of hookworms on metabolic health.; (© 2023. The Author(s).) |
| References: | Science. 2002 Apr 19;296(5567):490-4. (PMID: 11964470); Clin Transl Gastroenterol. 2020 Dec;11(12):e00274. (PMID: 33512796); BMC Med Res Methodol. 2017 Dec 6;17(1):162. (PMID: 29207961); Am J Trop Med Hyg. 2018 Nov;99(5):1186-1193. (PMID: 30226132); Lancet Infect Dis. 2021 Dec;21(12):1725-1736. (PMID: 34419209); Mucosal Immunol. 2022 Jun;15(6):1224-1233. (PMID: 35732819); Clin Infect Dis. 2020 Jul 27;71(3):601-613. (PMID: 31504336); Diabetes Res Clin Pract. 2016 Oct;120:209-20. (PMID: 27596058); Science. 2011 Apr 8;332(6026):243-7. (PMID: 21436399); PLoS One. 2013;8(1):e54855. (PMID: 23365679); Parasitol Int. 2020 Apr;75:102000. (PMID: 31669292); J Clin Invest. 2005 May;115(5):1111-9. (PMID: 15864338); J Clin Endocrinol Metab. 2013 Feb;98(2):E283-7. (PMID: 23275524); J Vet Med Sci. 2017 Jan 10;78(12):1855-1864. (PMID: 27665994); PLoS One. 2015 Jun 10;10(6):e0127746. (PMID: 26061042); BMJ. 2019 Apr 9;365:l1476. (PMID: 30967483); Nature. 2006 Dec 14;444(7121):860-7. (PMID: 17167474); J Allergy Clin Immunol. 2015 Feb;135(2):508-16. (PMID: 25248819); JAMA Neurol. 2020 Sep 1;77(9):1089-1098. (PMID: 32539079); Parasit Vectors. 2022 Jul 8;15(1):242. (PMID: 35804460); J Egypt Soc Parasitol. 2017 Apr;47(1):137-143. (PMID: 30157342); PLoS Pathog. 2020 May 14;16(5):e1008508. (PMID: 32407385); Clin Infect Dis. 2019 Aug 1;69(4):697-704. (PMID: 30407548); BMC Infect Dis. 2015 Mar 18;15:133. (PMID: 25888525); Clin Infect Dis. 2017 Sep 1;65(5):764-771. (PMID: 28472383); Infect Immun. 2013 Jun;81(6):1905-14. (PMID: 23509143); J Clin Invest. 2003 Dec;112(12):1821-30. (PMID: 14679177); Nat Commun. 2022 Aug 15;13(1):4770. (PMID: 35970829); Acta Trop. 2018 Apr;180:33-41. (PMID: 29309743); PLoS Negl Trop Dis. 2021 May 26;15(5):e0009395. (PMID: 34038411); Parasite Immunol. 2017 May;39(5):. (PMID: 27925245); FASEB J. 2015 Jul;29(7):3027-39. (PMID: 25852044); BMC Endocr Disord. 2019 Dec 11;19(1):136. (PMID: 31829172); Nature. 2012 Oct 4;490(7418):55-60. (PMID: 23023125); Diabetes Care. 2004 Jun;27(6):1487-95. (PMID: 15161807); Clin Transl Immunology. 2019 Nov 07;8(11):e01089. (PMID: 31719981); Nat Med. 2020 Mar;26(3):326-332. (PMID: 32066978); Parasite Immunol. 2015 Jul;37(7):333-9. (PMID: 25809087); J Infect Dis. 2014 Nov 1;210(9):1431-4. (PMID: 24795483); Front Endocrinol (Lausanne). 2021 Aug 12;12:728396. (PMID: 34456879); Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1039-49. (PMID: 18356555); PLoS One. 2012;7(8):e43134. (PMID: 22905215); Microbiol Insights. 2019 May 22;12:1178636119849934. (PMID: 31205419) |
| Molecular Sequence: | ANZCTR ACTRN12617000818336 |
| Entry Date(s): | Date Created: 20230726 Date Completed: 20230728 Latest Revision: 20250211 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10372076 |
| DOI: | 10.1038/s41467-023-40263-4 |
| PMID: | 37495576 |
| Database: | MEDLINE |
Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't