Skip to main content
Top
Published in: BMC Infectious Diseases 1/2022

01-12-2022 | Obesity | Research

Insulin resistance in people living with HIV is associated with exposure to thymidine analogues and/or didanosine and prior immunodeficiency

Authors: Julie Høgh, Malene Hove-Skovsgaard, Marco Gelpi, Anne Marie Reimer Jensen, Jan Gerstoft, Thomas Benfield, Heidi Storgaard, Susanne Dam Nielsen

Published in: BMC Infectious Diseases | Issue 1/2022

Login to get access

Abstract

Background

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.

Methods

We included well-treated PLWH without hepatitis co-infection, and with available fasting serum insulin and plasma glucose (n = 643) 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.

Results

Median (IQR) age of PLWH was 52 years (46–61), and 87% (n = 557) were male. Median (IQR) HOMA-IR was 1.86 (1.23–3.14) mmol/L × mU/L. Risk factors significantly associated with high HOMA-IR included older age, BMI ≥ 25, abdominal obesity, waist circumference, use of thymidine analogues and/or didanosine, time with HIV, and CD4+ nadir < 200 cells/µL.

Conclusions

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.
Literature
1.
go back to reference 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):810–8.CrossRef 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):810–8.CrossRef
2.
go back to reference 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):1179–84.CrossRef 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):1179–84.CrossRef
3.
go back to reference 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 2009–2010. BMJ Open Diabetes Res Care. 2017;5(1):e000304.CrossRef 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 2009–2010. BMJ Open Diabetes Res Care. 2017;5(1):e000304.CrossRef
4.
go back to reference Høgh 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):e32–5.CrossRef Høgh 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):e32–5.CrossRef
5.
go back to reference 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.CrossRef 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.CrossRef
6.
go back to reference Fletcher B, Gulanick M, Lamendola C. Risk factors for type 2 diabetes mellitus. J Cardiovasc Nurs. 2002;16(2):17–23.CrossRef Fletcher B, Gulanick M, Lamendola C. Risk factors for type 2 diabetes mellitus. J Cardiovasc Nurs. 2002;16(2):17–23.CrossRef
7.
go back to reference Westphal SA. Obesity, abdominal obesity, and insulin resistance. Clin Cornerstone. 2008;9(1):23–31.CrossRef Westphal SA. Obesity, abdominal obesity, and insulin resistance. Clin Cornerstone. 2008;9(1):23–31.CrossRef
8.
go back to reference Rönnemaa 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):383–7.PubMed Rönnemaa 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):383–7.PubMed
9.
go back to reference 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):1224–9.CrossRef 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):1224–9.CrossRef
10.
go back to reference 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.CrossRef 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.CrossRef
11.
go back to reference 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):675–83.CrossRef 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):675–83.CrossRef
12.
go back to reference 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.CrossRef 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.CrossRef
13.
go back to reference 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.CrossRef 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.CrossRef
14.
go back to reference Department of Nutrition for Health and Development - World Health Organization. Waist circumference and waist-hip ratio—Report of a WHO Expert Consultation. Geneva: World Health Organization; 2008. Department of Nutrition for Health and Development - World Health Organization. Waist circumference and waist-hip ratio—Report of a WHO Expert Consultation. Geneva: World Health Organization; 2008.
15.
go back to reference 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):507–20.CrossRef 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):507–20.CrossRef
16.
go back to reference Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.CrossRef Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.CrossRef
17.
go back to reference 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.CrossRef 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.CrossRef
18.
go back to reference 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):579–86.CrossRef 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):579–86.CrossRef
19.
go back to reference 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.CrossRef 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.CrossRef
20.
go back to reference Murata H, Hruz PW, Mueckler M. Indinavir inhibits the glucose transporter isoform Glut4 at physiologic concentrations. AIDS. 2002;16(6):859–63.CrossRef Murata H, Hruz PW, Mueckler M. Indinavir inhibits the glucose transporter isoform Glut4 at physiologic concentrations. AIDS. 2002;16(6):859–63.CrossRef
21.
go back to reference Murata H, Hruz PW, Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem. 2000;275(27):20251–4.CrossRef Murata H, Hruz PW, Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem. 2000;275(27):20251–4.CrossRef
22.
go back to reference 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.CrossRef 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.CrossRef
23.
go back to reference 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):993–1000.CrossRef 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):993–1000.CrossRef
Metadata
Title
Insulin resistance in people living with HIV is associated with exposure to thymidine analogues and/or didanosine and prior immunodeficiency
Authors
Julie Høgh
Malene Hove-Skovsgaard
Marco Gelpi
Anne Marie Reimer Jensen
Jan Gerstoft
Thomas Benfield
Heidi Storgaard
Susanne Dam Nielsen
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2022
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-022-07485-1

Other articles of this Issue 1/2022

BMC Infectious Diseases 1/2022 Go to the issue