{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:53:48Z","timestamp":1790952828545,"version":"4.1.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,5,28]],"date-time":"2022-05-28T00:00:00Z","timestamp":1653696000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,28]],"date-time":"2022-05-28T00:00:00Z","timestamp":1653696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordic Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rigshospitalet Research Council"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>As people living with HIV (PLWH) are growing older, there is increased incidence of metabolic diseases, including type 2 diabetes mellitus, for which insulin resistance is a key determinant. In this study, we aimed to investigate risk factors associated with insulin resistance in PLWH.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We included well-treated PLWH without hepatitis co-infection, and with available fasting serum insulin and plasma glucose (n\u2009=\u2009643) from the Copenhagen Comorbidity in HIV Infection Study. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). We investigated the association between risk factors and high HOMA-IR in a logistic regression model adjusted for age, sex, abdominal obesity, smoking status, and origin. When including use of thymidine analogues and\/or didanosine in the model, we also adjusted for time with HIV.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Median (IQR) age of PLWH was 52\u00a0years (46\u201361), and\u00a087% (n\u2009=\u2009557) were male. Median (IQR) HOMA-IR was 1.86 (1.23\u20133.14)\u00a0mmol\/L\u00a0\u00d7\u00a0mU\/L. Risk factors significantly associated with high HOMA-IR included older age, BMI\u2009\u2265\u200925, abdominal obesity, waist circumference, use of thymidine analogues and\/or didanosine, time with HIV, and CD4<jats:sup>+<\/jats:sup> nadir\u2009&lt;\u2009200\u00a0cells\/\u00b5L.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Insulin resistance in PLWH is associated with both use of thymidine analogues and\/or didanosine and prior immunodeficiency suggesting that increased attention on blood glucose in these patients could be beneficial.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12879-022-07485-1","type":"journal-article","created":{"date-parts":[[2022,5,28]],"date-time":"2022-05-28T06:02:43Z","timestamp":1653717763000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Insulin resistance in people living with HIV is associated with exposure to thymidine analogues and\/or didanosine and prior immunodeficiency"],"prefix":"10.1186","volume":"22","author":[{"given":"Julie","family":"H\u00f8gh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malene","family":"Hove-Skovsgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Gelpi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Marie Reimer","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Gerstoft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Benfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Storgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne Dam","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,28]]},"reference":[{"issue":"7","key":"7485_CR1","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/S1473-3099(15)00056-0","volume":"15","author":"M Smit","year":"2015","unstructured":"Smit M, Brinkman K, Geerlings S, Smit C, Thyagarajan K, van Sighem AV, et al. Future challenges for clinical care of an ageing population infected with HIV: a modelling study. Lancet Infect Dis. 2015;15(7):810\u20138.","journal-title":"Lancet Infect Dis"},{"issue":"10","key":"7485_CR2","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1001\/archinte.165.10.1179","volume":"165","author":"TT Brown","year":"2005","unstructured":"Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study [published correction appears in Arch Intern Med. 2005 Nov 28;165(21):2541]. Arch Intern Med. 2005;165(10):1179\u201384.","journal-title":"Arch Intern Med"},{"issue":"1","key":"7485_CR3","doi-asserted-by":"publisher","first-page":"e000304","DOI":"10.1136\/bmjdrc-2016-000304","volume":"5","author":"AC Hernandez-Romieu","year":"2017","unstructured":"Hernandez-Romieu AC, Garg S, Rosenberg ES, Thompson-Paul AM, Skarbinski J. Is diabetes prevalence higher among HIV-infected individuals compared with the general population? Evidence from MMP and NHANES 2009\u20132010. BMJ Open Diabetes Res Care. 2017;5(1):e000304.","journal-title":"BMJ Open Diabetes Res Care"},{"issue":"4","key":"7485_CR4","doi-asserted-by":"publisher","first-page":"e32","DOI":"10.1097\/QAI.0000000000002798","volume":"88","author":"J H\u00f8gh","year":"2021","unstructured":"H\u00f8gh J, Gelpi M, Skovsgaard MH, Afzal S, Nordestgaard BG, Gerstoft J, et al. HIV infection is associated with type 2 diabetes mellitus. J Acquir Immune Defic Syndr. 2021;88(4):e32\u20135.","journal-title":"J Acquir Immune Defic Syndr"},{"key":"7485_CR5","doi-asserted-by":"publisher","first-page":"514","DOI":"10.3389\/fendo.2018.00514","volume":"9","author":"MN Pedro","year":"2018","unstructured":"Pedro MN, Rocha GZ, Guadagnini D, Santos A, Magro DO, Assalin HB, et al. Insulin resistance in HIV-patients: causes and consequences. Front Endocrinol. 2018;9:514.","journal-title":"Front Endocrinol"},{"issue":"2","key":"7485_CR6","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1097\/00005082-200201000-00003","volume":"16","author":"B Fletcher","year":"2002","unstructured":"Fletcher B, Gulanick M, Lamendola C. Risk factors for type 2 diabetes mellitus. J Cardiovasc Nurs. 2002;16(2):17\u201323.","journal-title":"J Cardiovasc Nurs"},{"issue":"1","key":"7485_CR7","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S1098-3597(08)60025-3","volume":"9","author":"SA Westphal","year":"2008","unstructured":"Westphal SA. Obesity, abdominal obesity, and insulin resistance. Clin Cornerstone. 2008;9(1):23\u201331.","journal-title":"Clin Cornerstone"},{"issue":"2","key":"7485_CR8","first-page":"383","volume":"82","author":"T R\u00f6nnemaa","year":"1997","unstructured":"R\u00f6nnemaa T, Koskenvuo M, Marniemi J, Koivunen T, Sajantila A, Rissanen A, et al. Glucose metabolism in identical twins discordant for obesity. The critical role of visceral fat 1. J Clin Endocrinol Metab. 1997;82(2):383\u20137.","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"7485_CR9","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.2337\/dc07-2013","volume":"31","author":"S De Wit","year":"2008","unstructured":"De Wit S, Sabin CA, Weber R, Worm SW, Reiss P, Cazanave C, et al. Incidence and risk factors for new-onset diabetes in HIV-infected patients. Diabetes Care. 2008;31(6):1224\u20139.","journal-title":"Diabetes Care"},{"issue":"9","key":"7485_CR10","doi-asserted-by":"publisher","first-page":"e44575","DOI":"10.1371\/journal.pone.0044575","volume":"7","author":"LD Rasmussen","year":"2012","unstructured":"Rasmussen LD, Mathiesen ER, Kronborg G, Pedersen C, Gerstoft J, Obel N. Risk of diabetes mellitus in persons with and without HIV: A Danish nationwide population-based cohort study. PLoS ONE. 2012;7(9):e44575.","journal-title":"PLoS ONE"},{"issue":"4","key":"7485_CR11","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1097\/QAD.0000000000002119","volume":"33","author":"M Gelpi","year":"2019","unstructured":"Gelpi M, Afzal S, Fuchs A, Lundgren J, Knudsen AD, Drivsholm N, et al. Prior exposure to thymidine analogs and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors. AIDS. 2019;33(4):675\u201383.","journal-title":"AIDS"},{"issue":"1","key":"7485_CR12","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1186\/s12879-019-4347-y","volume":"19","author":"M Gelpi","year":"2019","unstructured":"Gelpi M, Knudsen AD, Larsen KB, Mocroft A, Lebech AM, Lindegaard B, et al. Long-lasting alterations in adipose tissue density and adiponectin production in people living with HIV after thymidine analogues exposure. BMC Infect Dis. 2019;19(1):708.","journal-title":"BMC Infect Dis"},{"issue":"1","key":"7485_CR13","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1186\/s12879-016-2026-9","volume":"16","author":"A Ronit","year":"2016","unstructured":"Ronit A, Haissman J, Kirkegaard-Klitbo DM, Kristensen TS, Lebech AM, Benfield T, et al. Copenhagen comorbidity in HIV infection (COCOMO) study: a study protocol for a longitudinal, non-interventional assessment of non-AIDS comorbidity in HIV infection in Denmark. BMC Infect Dis. 2016;16(1):713.","journal-title":"BMC Infect Dis"},{"key":"7485_CR14","volume-title":"Waist circumference and waist-hip ratio\u2014Report of a WHO Expert Consultation","author":"Department of Nutrition for Health and Development - World Health Organization","year":"2008","unstructured":"Department of Nutrition for Health and Development - World Health Organization. Waist circumference and waist-hip ratio\u2014Report of a WHO Expert Consultation. Geneva: World Health Organization; 2008."},{"issue":"5","key":"7485_CR15","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1001\/jama.2013.284427","volume":"311","author":"PA James","year":"2014","unstructured":"James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA J Am Med Assoc. 2014;311(5):507\u201320.","journal-title":"JAMA J Am Med Assoc"},{"issue":"7","key":"7485_CR16","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1007\/BF00280883","volume":"28","author":"DR Matthews","year":"1985","unstructured":"Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412\u20139.","journal-title":"Diabetologia"},{"issue":"1","key":"7485_CR17","doi-asserted-by":"publisher","first-page":"e15","DOI":"10.1152\/ajpendo.00645.2007","volume":"294","author":"R Muniyappa","year":"2008","unstructured":"Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol - Endocrinol Metab. 2008;294(1):e15-26.","journal-title":"Am J Physiol - Endocrinol Metab"},{"issue":"4","key":"7485_CR18","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1093\/cid\/ciy146","volume":"67","author":"M Gelpi","year":"2018","unstructured":"Gelpi M, Afzal S, Lundgren J, Ronit A, Roen A, Mocroft A, et al. Higher risk of abdominal obesity, elevated low-density lipoprotein cholesterol, and hypertriglyceridemia, but not of hypertension, in people living with human immunodeficiency virus (HIV): results from the Copenhagen comorbidity in HIV infection study. Clin Infect Dis. 2018;67(4):579\u201386.","journal-title":"Clin Infect Dis"},{"key":"7485_CR19","doi-asserted-by":"publisher","first-page":"108050","DOI":"10.1016\/j.diabres.2020.108050","volume":"161","author":"WC Wu","year":"2020","unstructured":"Wu WC, Wei JN, Chen SC, Fan KC, Lin CH, Yang CY, et al. Progression of insulin resistance: a link between risk factors and the incidence of diabetes. Diabetes Res Clin Pract. 2020;161:108050.","journal-title":"Diabetes Res Clin Pract"},{"issue":"6","key":"7485_CR20","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1097\/00002030-200204120-00005","volume":"16","author":"H Murata","year":"2002","unstructured":"Murata H, Hruz PW, Mueckler M. Indinavir inhibits the glucose transporter isoform Glut4 at physiologic concentrations. AIDS. 2002;16(6):859\u201363.","journal-title":"AIDS"},{"issue":"27","key":"7485_CR21","doi-asserted-by":"publisher","first-page":"20251","DOI":"10.1074\/jbc.C000228200","volume":"275","author":"H Murata","year":"2000","unstructured":"Murata H, Hruz PW, Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem. 2000;275(27):20251\u20134.","journal-title":"J Biol Chem"},{"issue":"1","key":"7485_CR22","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12879-016-2099-5","volume":"17","author":"V Spagnuolo","year":"2017","unstructured":"Spagnuolo V, Galli L, Poli A, Salpietro S, Gianotti N, Piatti P, et al. Associations of statins and antiretroviral drugs with the onset of type 2 diabetes among HIV-1-infected patients. BMC Infect Dis. 2017;17(1):43.","journal-title":"BMC Infect Dis"},{"issue":"6","key":"7485_CR23","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1016\/j.amjcard.2015.12.037","volume":"117","author":"MI Brener","year":"2016","unstructured":"Brener MI, Post WS, Haberlen SA, Zhang L, Palella FJ, Jacobson LP, et al. Comparison of insulin resistance to coronary atherosclerosis in human immunodeficiency virus infected and uninfected men (from the Multicenter AIDS Cohort Study). Am J Cardiol. 2016;117(6):993\u20131000.","journal-title":"Am J Cardiol"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-022-07485-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12879-022-07485-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-022-07485-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,28]],"date-time":"2022-05-28T18:02:55Z","timestamp":1653760975000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-022-07485-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,28]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["7485"],"URL":"https:\/\/doi.org\/10.1186\/s12879-022-07485-1","relation":{},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,28]]},"assertion":[{"value":"25 January 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval was obtained by the Regional Ethics Committee of Copenhagen (H-8-2014-004). The study was performed in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"J.H reports grant from Novo Nordisk Foundation and Righospitalet Research Council. M.H.S, M.G, A.M.R.J and J.G reports no conflicts of interest. T.B reports grants from Novo Nordisk Foundation, grants from Simonsen Foundation, grants and personal fees from GSK, grants and personal fees from Pfizer, personal fees from Boehringer Ingelheim, grants and personal fees from Gilead, personal fees from MSD, personal fees from Astra Zeneca, personal fees from Janssen, grants from Lundbeck Foundation, grants from Kai Hansen Foundation, personal fees from Pentabase ApS, grants from Erik and Susanna Olesen\u2019s Charitable Fund, outside the submitted work. H.S reports Steno Collaborative Grant, Novo Nordisk Foundation and advisory board activity for Novo Nordisk. S.D.N. has received unrestricted research grants from Novo Nordisk Foundation, Lundbeck Foundation, Rigshospitalet Research Council. Travelling grants from Gilead. Advisory board activity for Gilead and MSD, all unrelated to this manuscript. All other authors report no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"503"}}