The role of a traditional and western diet on glucose homeostasis in Greenlandic Inuit carriers and non-carriers of type 2 diabetes variant in the TBC1D4 gene: A protocol for a randomized clinical trial

Grith Møller, Mads Vendelbo Lind, Aviaja Lyberth Hauptmann, Ninna Senftleber, Charlotte Brandstrup Hansen, Torben Hansen, Marit Eika Jørgensen, Lotte Lauritzen, Grith Møller, Mads Vendelbo Lind, Aviaja Lyberth Hauptmann, Ninna Senftleber, Charlotte Brandstrup Hansen, Torben Hansen, Marit Eika Jørgensen, Lotte Lauritzen

Abstract

Introduction: The lifestyle of Inuit in Greenland and worldwide is undergoing a transition from a fisher-hunter to a westernized society and meanwhile the prevalence of type-2 diabetes (T2D) has increased dramatically. Studies have shown that a common nonsense p.Arg684Ter variant in TBC1D4, which is frequent in Greenland, confers genetic susceptibility towards high risk of T2D. The aim of the study is to investigate whether a traditional marine diet, with high fat and low carbohydrate, will improve glycemic control in Greenland Inuit compared to a western diet. Moreover, we want to examine if the response is more pronounced in carriers of the p.Arg684Ter variant.

Materials and methods: We will conduct a randomized, clinical cross-over trial with two dietary intervention periods of four weeks duration. The diet intervention comprise provision of >20E% and instruction for the remaining part of the diet. We expect to include 30 homozygous carriers and 30 homozygous non-carriers of the p.Arg684Ter variant, aged 18-80 years, across three Greenlandic towns. The primary outcome is plasma (p)-glucose 2 h post an oral glucose tolerance test and we aim to have 80% power, at α = 0.05, to detect a difference of 1.1 mmol/L. We will also include supporting measures of glucose homeostasis, assess other markers of the metabolic syndrome and perform metabolome and microbiome profiling. The statistical analysis will be performed as complete case analyses using linear mixed models.

Ethics and dissemination: The study received approval by the Ethics Committee of Greenland (KVUG 2018-26) and will be disseminated via international peer-reviewed journal articles and conferences.

Trial registration number: Clinicaltrials.gov identifier no. NCT04011904.

Keywords: Diet; E%, energy percentage; Glucose metabolism; Inuit; Lifestyle; OGTT, oral glucose tolerance test; T2D, type 2 diabetes; TBC1D4; Type 2 diabetes.

Conflict of interest statement

MEJ has received funding from AstraZeneca, Sanofi Aventis, Boehringer Ingelheim and AMGEN. MEJ own shares in Novo Nordisk A/S. The other authors have nothing to disclose.

© 2021 Published by Elsevier Inc.

Figures

Fig. 1
Fig. 1
Study outline – The individuals are recruited from the Population Survey in Greenland 1999 and the Inuit Health in Transition studies and after screening they are randomized to start with either the traditional Inuit diet or a westernized diet. The present study consists of two, 4-week periods and sampling will be conducted before and after each intervention period.

References

    1. Moltke I., Fumagalli M., Korneliussen T.S., Crawford J.E., Bjerregaard P., Jørgensen M.E., Grarup N., Gulløv H.C., Linneberg A., Pedersen O., Hansen T., Nielsen R., Albrechtsen A. Uncovering the genetic history of the present-day Greenlandic population. Am. J. Hum. Genet. 2015;96:54–69. doi: 10.1016/j.ajhg.2014.11.012.
    1. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee Canadian diabetes association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada: type 2 diabetes in aboriginal peoples. Can. J. Diabetes. 2013;37(suppl) S1–S212.
    1. Jeppesen C., Jørgensen M.E., Bjerregaard P. Assessment of consumption of marine food in Greenland by a food frequency questionnaire and biomarkers. Int. J. Circumpolar Health. 2012;71:18361. doi: 10.3402/ijch.v71i0.18361.
    1. Jorgensen M.E., Bjeregaard P., Borch-Johnsen K., Backer V., Becker U., Jorgensen T., Mulvad G. Diabetes and impaired glucose tolerance among the inuit population of Greenland. Diabetes Care. 2002;25:1766–1771. doi: 10.2337/diacare.25.10.1766.
    1. Moltke I., Grarup N., Jørgensen M.E., Bjerregaard P., Treebak J.T., Fumagalli M., Korneliussen T.S., Andersen M.A., Nielsen T.S., Krarup N.T., Gjesing A.P., Zierath J.R., Linneberg A., Wu X., Sun G., Jin X., Al-Aama J., Wang J., Borch-Johnsen K., Pedersen O., Nielsen R., Albrechtsen A., Hansen T. A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes. Nature. 2014;512:190–193. doi: 10.1038/nature13425.
    1. Hegele R.A., Young T.K., Connelly P.W. Are Canadian Inuit at increased genetic risk for coronary heart disease? J. Mol. Med. 1997;75:364–370. doi: 10.1007/s001090050122.
    1. Jørgensen M.E., Borch-Johnsen K., Witte D.R., Bjerregaard P. Diabetes in Greenland and its relationship with urbanization. Diabet. Med. 2012;29:755–760. doi: 10.1111/j.1464-5491.2011.03527.x.
    1. Yusuf S., Reddy S., Ôunpuu S., Anand S. Global burden of cardiovascular diseases. Part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation. 2001;104:2746–2753. doi: 10.1161/hc4601.099487.
    1. Jørgensen M.E., Bjerregaard P., Kjærgaard J.J., Borch-Johnsen K. High prevalence of markers of coronary heart disease among Greenland Inuit. Atherosclerosis. 2008;196:772–778. doi: 10.1016/j.atherosclerosis.2007.01.008.
    1. Jeppesen C., Bjerregaard P., Jørgensen M.E. Dietary patterns in Greenland and their relationship with type 2 diabetes mellitus and glucose intolerance. Publ. Health Nutr. 2014;17:462–470. doi: 10.1017/S136898001300013X.
    1. Andersen M.K., Hansen T. Genetics of metabolic traits in Greenlanders: lessons from an isolated population. J. Intern. Med. 2018;284:464–477. doi: 10.1111/joim.12814.
    1. Bjerregaard P., Mulvad G. The best of two worlds: how the Greenland board of nutrition has handled conflicting evidence about diet and health. Int. J. Circumpolar Health. 2012;71:1–5. doi: 10.3402/ijch.v71i0.18588.
    1. Bjerregaard P., Jeppesen C. Inuit dietary patterns in modern Greenland. Int. J. Circumpolar Health. 2010;69:13–24. doi: 10.3402/ijch.v69i1.17387.
    1. Deutch B., Dyerberg J., Pedersen H.S., Aschlund E., Hansen J.C. Traditional and modern Greenlandic food - dietary composition, nutrients and contaminants. Sci. Total Environ. 2007;384:106–119. doi: 10.1016/j.scitotenv.2007.05.042.
    1. P Bjerregaard S.A.&V.B., Curtis T., Borch-Johnsen K., Mulvad G., Becker U. Inuit health in Greenland: a population survey of life style and disease in Greenland and among Inuit living in Denmark. Int. J. Circumpolar Health. 2003 doi: 10.3402/ijch.v62i0.18212.
    1. , (n.d.).
    1. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus. Diabetes Res. Clin. Pract. 2011;93:299–309. doi: 10.1016/j.diabres.2011.03.012.
    1. Hauptmann A.L., Paulová P., Castro-Mejía J.L., Hansen L.H., Sicheritz-Pontén T., Mulvad G., Nielsen D.S. The microbial composition of dried fish prepared according to Greenlandic Inuit traditions and industrial counterparts. Food Microbiol. 2020;85:103305. doi: 10.1016/j.fm.2019.103305.
    1. Metherel A.H., Stark K.D. The stability of blood fatty acids during storage and potential mechanisms of degradation: a review. Prostaglandins Leukot. Essent. Fatty Acids. 2016;104:33–43. doi: 10.1016/j.plefa.2015.12.003.
    1. Sano H., Kane S., Sano E., Mı^inea C.P., Asara J.M., Lane W.S., Garner C.W., Lienhard G.E. Insulin-stimulated phosphorylation of a rab GTPase-activating protein regulates GLUT4 translocation. J. Biol. Chem. 2003;278:14599–14602. doi: 10.1074/jbc.C300063200.
    1. Claw K.G., Anderson M.Z., Begay R.L., Tsosie K.S., Fox K., Garrison N.A., Bader A.C.C., Bardill J., Bolnick D.A.A., Brooks J., Cordova A., Malhi R.S., Nakatsuka N., Neller A., Raff J.A.A., Singson J., TallBear K., Vargas T., Yracheta J.M. A framework for enhancing ethical genomic research with Indigenous communities. Nat. Commun. 2018;9 doi: 10.1038/s41467-018-05188-3.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera