Purpose of Review
This review seeks to address the epidemiology and pathophysiological basis of the interaction between HIV infection and diabetes and the implication for treatment. Its importance stems from the current context of the growing burden of both conditions and the possible mechanisms of interactions that may exist but not yet sufficiently examined.
HIV infection is associated with increased risk of insulin resistance, and ART is associated with metabolic derangement and the occurrence of type 2 diabetes. The increasing survival among people with HIV infection in developing countries is paralleled by a growing burden of chronic non-communicable diseases (NCDs) especially cardiovascular diseases and diabetes mellitus. The prevalence of diabetes mellitus is higher in HIV-positive persons compared to the general population, and especially those with associated hepatitis C virus (HCV) co-infection. Antiretroviral therapy (ART) during chronic HIV infection is the most incriminated risk factor for the development of diabetes mellitus through diverse mechanisms depending on the ART leading to insulin resistance and increased inflammatory status.
A staggering 629 million of people 20–79 years are projected to have diabetes by 2045 while the world will soon enter the fourth decade of the HIV infection. Classical risk factors for diabetes such as physical inactivity and unhealthy diet may not solely explain the current trends, suggesting the role of novel risk factors including infections/inflammation. HIV and its treatment have been identified as potential contributors. Co-infections frequently observed during HIV infection also significantly influence both the epidemiological and pathophysiological of the link between HIV and diabetes. Although the relative contribution of each risk factor has not yet been quantified, several lines of evidence suggest that ART is a major contributor to hyperglycemia in HIV infection. ARTs have also led to an increase in metabolic dysfunction, including insulin resistance syndromes, dyslipidemia, and lipodystrophy. The association between ARTs and the risk of developing diabetes therefore calls for a careful choice of medication and evaluation of the risk of developing diabetes.
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DeFronzo RA, Ferrannini E, Alberti KGMM, Zimmet P. International textbook of diabetes mellitus, 4th ed. Chichester, West Sussex ; Hoboken, NJ: John Wiley & Sons Inc; 2015.
International Diabetes Federation. IDF diabetes atlas. 8th edn. Brussels, Belgium: International Diabetes Federation; 2017.
Joint United Nations Programme on HIV/AIDS (UNAIDS). 2017. http://www.unaids.org/en/resources/documents/2017/2017_data_book.
•• Atun R, Davies JI, Gale EAM, Bärnighausen T, Beran D, Kengne AP, et al. Diabetes in sub-Saharan Africa: from clinical care to health policy. Lancet Diabetes Endocrinol. 2017;5(8):622–67. This study showcases broadly the epidemiological profile of diabetes in sub-Saharan Africa and the contribution of HIV and ART towards the surge of diabetes prevalence in SSA.
• Pepin ME, Padgett LE, McDowell RE, Burg AR, Brahma MK, Holleman C, et al. Antiretroviral therapy potentiates high-fat diet induced obesity and glucose intolerance. Mol Metab. 2018;12:48–61. This study proposes a possible mechanism for the development of obesity and glucose intolerance (major risk factor for diabetes) during Protease Inhibitor-based HIV regimen.
White DL, Ratziu V, El-Serag HB. Hepatitis C infection and risk of diabetes: a systematic review and meta-analysis. J Hepatol. 2008;49(5):831–44.
Dooley KE, Chaisson RE. Tuberculosis and diabetes mellitus: convergence of two epidemics. Lancet Infect Dis. 2009;9(12):737–46.
El-Sadr WM, Mullin CM, Carr A, Gibert C, Rappoport C, Visnegarwala F, et al. Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral-naive cohort. HIV Med. 2005;6(2):114–21.
Kilby JM, Tabereaux PB. Severe hyperglycemia in an HIV clinic: preexisting versus drug-associated diabetes mellitus. J Acquir Immune Defic Syndr Hum Retrovirol. 1998;17(1):46–50.
Visnegarwala F, Krause KL, Musher DM. Severe diabetes associated with protease inhibitor therapy. Ann Intern Med. 1997;127(10):947.
Eastone JA, Decker CF. New-onset diabetes mellitus associated with use of protease inhibitor. Ann Intern Med. 1997;127(10):948.
Dubé MP, Johnson DL, Currier JS, Leedom JM. Protease inhibitor-associated hyperglycaemia. Lancet Lond Engl. 1997;350(9079):713–4.
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. Arch Intern Med. 2005;165(10):1179–84.
Petoumenos K, Worm SW, Fontas E, Weber R, De Wit S, Bruyand M, et al. Predicting the short-term risk of diabetes in HIV-positive patients: the data collection on adverse events of anti-HIV drugs (D:a:D) study. J Int AIDS Soc. 2012;15(2):17426.
Ledergerber B, Furrer H, Rickenbach M, Lehmann R, Elzi L, Hirschel B, et al. Factors associated with the incidence of type 2 diabetes mellitus in HIV-infected participants in the Swiss HIV cohort study. Clin Infect Dis. 2007;45(1):111–9.
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.
Samad F, Harris M, Puskas CM, Ye M, Chia J, Chacko S, et al. Incidence of diabetes mellitus and factors associated with its development in HIV-positive patients over the age of 50. BMJ Open Diabetes Res Care. 2017;5(1):e000457.
• 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. This study demonstrates that the risk of developing diabetes in an HIV-infected population is higher than that of the general population.
Ghislain M, Bastard J-P, Meyer L, Capeau J, Fellahi S, Gérard L, et al. Late antiretroviral therapy (ART) initiation is associated with long-term persistence of systemic inflammation and metabolic abnormalities. PLoS One. 2015;10(12):e0144317.
Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV outpatient study investigators. N Engl J Med. 1998;338(13):853–60.
Larsson A, Larsson SE. The effects of ethylene-1-hydroxy-1, 1-diphosphonate on cellular transformation and organic matrix of the epiphyseal growth plate of the rat--a light microscopic and ultrastructural study. Acta Pathol Microbiol Scand A. 1978;86(3):211–23.
Samaras K. The burden of diabetes and hyperlipidemia in treated HIV infection and approaches for cardiometabolic care. Curr HIV/AIDS Rep. 2012;9(3):206–17.
Woerle HJ, Mariuz PR, Meyer C, Reichman RC, Popa EM, Dostou JM, et al. Mechanisms for the deterioration in glucose tolerance associated with HIV protease inhibitor regimens. Diabetes. 2003;52(4):918–25.
Kalra S, Kalra B, Agrawal N, Unnikrishnan A. Understanding diabetes in patients with HIV/AIDS. Diabetol Metab Syndr. 2011;3:2.
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: the data collection on adverse events of anti-HIV drugs (D:a:D) study. Diabetes Care. 2008;31(6):1224–9.
Erlandson KM, Kitch D, Tierney C, Sax PE, Daar ES, Melbourne KM, et al. Impact of randomized antiretroviral therapy initiation on glucose metabolism. AIDS Lond Engl. 2014;28(10):1451–61.
Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS Lond Engl. 1998;12(7):F51–8.
Vigouroux C, Maachi M, Nguyên T-H, Coussieu C, Gharakhanian S, Funahashi T, et al. Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy. AIDS Lond Engl. 2003;17(10):1503–11.
Samaras K. Prevalence and pathogenesis of diabetes mellitus in HIV-1 infection treated with combined antiretroviral therapy. J Acquir Immune Defic Syndr. 2009;50(5):499–505.
Carr A. HIV protease inhibitor-related lipodystrophy syndrome. Clin Infect Dis. 2000;30(Suppl 2):S135–42.
Zannou DM, Denoeud L, Lacombe K, Amoussou-Guenou D, Bashi J, Akakpo J, et al. Incidence of lipodystrophy and metabolic disorders in patients starting non-nucleoside reverse transcriptase inhibitors in Benin. Antivir Ther. 2009;14(3):371–80.
Dagogo-Jack S. HIV therapy and diabetes risk. Diabetes Care. 2008;31(6):1267–8.
Mehta SH, Brancati FL, Sulkowski MS, Strathdee SA, Szklo M, Thomas DL. Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Ann Intern Med. 2000;133(8):592–9.
Williams RH, Larsen PR, éditeurs. Williams textbook of endocrinology. 10th ed. Philadelphia, Pa: Saunders; 2003. 1927 p.
Abrass CK. Fc-receptor-mediated phagocytosis: abnormalities associated with diabetes mellitus. Clin Immunol Immunopathol. 1991;58(1):1–17.
Nichols GP. Diabetes among young tuberculous patients; a review of the association of the two diseases. Am Rev Tuberc. 1957;76(6):1016–30.
Zack MB, Fulkerson LL, Stein E. Glucose intolerance in pulmonary tuberculosis. Am Rev Respir Dis. 1973;108(5):1164–9.
Oluboyo PO, Erasmus RT. The significance of glucose intolerance in pulmonary tuberculosis. Tubercle. 1990;71(2):135–8.
Başoğlu OK, Bacakoğlu F, Cok G, Sayiner A, Ateş M. The oral glucose tolerance test in patients with respiratory infections. Monaldi Arch Chest Dis. 1999;54(4):307–10.
Takarabe D, Rokukawa Y, Takahashi Y, Goto A, Takaichi M, Okamoto M, et al. Autoimmune diabetes in HIV-infected patients on highly active antiretroviral therapy. J Clin Endocrinol Metab. 2010;95(8):4056–60.
Smith JC, Evans LM, Wilkinson I, Goodfellow J, Cockcroft JR, Scanlon MF, et al. Effects of GH replacement on endothelial function and large-artery stiffness in GH-deficient adults: a randomized, double-blind, placebo-controlled study. Clin Endocrinol (Oxf). 56(4):493–501.
Lamanna C, Monami M, Marchionni N, Mannucci E. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2011;13(3):221–8.
Dolutegravir | FDA Label - Tablet (film coated) | AIDSinfo [Internet]. [cited 2018 Jul 31]. Available from: https://aidsinfo.nih.gov/drugs/509/dolutegravir/167/professional.
Monroe AK, Glesby MJ, Brown TT. Diagnosing and managing diabetes in HIV-infected patients: current concepts. Clin Infect Dis. 2015;60(3):453–62.
Mannucci E, Monami M, Lamanna C, Gensini GF, Marchionni N. Pioglitazone and cardiovascular risk. A comprehensive meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2008;10(12):1221–38.
Deeg MA, Buse JB, Goldberg RB, Kendall DM, Zagar AJ, Jacober SJ, et al. Pioglitazone and rosiglitazone have different effects on serum lipoprotein particle concentrations and sizes in patients with type 2 diabetes and dyslipidemia. Diabetes Care. 2007;30(10):2458–64.
Lewis JD, Ferrara A, Peng T, Hedderson M, Bilker WB, Quesenberry CP, et al. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care. 2011;34(4):916–22.
Schernthaner G, Currie CJ, Schernthaner G-H. Do we still need pioglitazone for the treatment of type 2 diabetes? A risk-benefit critique in 2013. Diabetes Care. 2013;36(Suppl 2):S155–61.
Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet Lond Engl. 2006;368(9548):1696–705.
Goodwin SR, Reeds DN, Royal M, Struthers H, Laciny E, Yarasheski KE. Dipeptidyl peptidase IV inhibition does not adversely affect immune or virological status in HIV infected men and women: a pilot safety study. J Clin Endocrinol Metab. 2013;98(2):743–51.
ONGLYZA® (saxagliptin) | Adult Type 2 Diabetes Medication [Internet]. [cited 2018 Jul 31]. Available from: https://www.onglyza.com/.
Neal B, Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Stein P, et al. Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS)--a randomized placebo-controlled trial. Am Heart J. 2013;166(2):217–223.e11.
INVOKANA® (canagliflozin) Dosing & Prescribing Information [Internet]. [cited 2018 Jul 31]. Available from: https://www.invokanahcp.com/dosing.
Murphy CS, McKay GA. HIV and diabetes. Diabetes Manag. 2013;3(6):495–503.
Conflict of Interest
Emile Camille Noubissi, Jean-Claude Katte, and Eugene Sobngwi declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
This article is part of the Topical Collection on Other Forms of Diabetes and Its Complications