Skip to main content

Diabetes in People with HIV

Abstract

Purpose of Review

To discuss the diagnosis, treatment, and complications of diabetes in people with HIV (PWH) and to review HIV-related factors that may contribute to the development of diabetes or alter decisions in the care and treatment of PWH with diabetes.

Recent Findings

For those patients with atherosclerotic cardiovascular disease, heart failure, and/or chronic kidney disease, GLP-1 receptor agonists and SGLT-2 inhibitors should be considered for use. Evidence for this recommendation is, however, based on studies that were not conducted in populations consisting solely of PWH.

Summary

Diabetes is a significant comorbidity in PWH and adds to their already heightened risk of cardiovascular disease. HIV-specific factors, including interactions of antiretroviral therapy with medications that either treat diabetes and/or prevent cardiovascular disease, should be evaluated.

This is a preview of subscription content, access via your institution.

References

  1. Buchacz K, Baker RK, Palella FJ, et al. Disparities in prevalence of key chronic diseases by gender and race/ethnicity among antiretroviral-treated HIV-infected adults in the US. Antivir Ther. 2013;18(1):65–75.

    PubMed  Google Scholar 

  2. Warriner AH, Burkholder GA, Overton ET. HIV-related metabolic comorbidities in the current ART era. Infect Dis Clin N Am. 2014;28(3):457-+.

    Google Scholar 

  3. Noubissi EC, Katte JC, Sobngwi E. Diabetes and HIV. Curr Diabetes Rep. 2018;18(11).

  4. Patel P, Rose CE, Collins PY, Nuche-Berenguer B, Sahasrabuddhe VV, Peprah E, et al. Noncommunicable diseases among HIV-infected persons in low-income and middle-income countries: a systematic review and meta-analysis. Aids. 2018;32:S5–S20.

    PubMed  PubMed Central  Google Scholar 

  5. Brown TT, Cole SR, Li XH, 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.

    PubMed  Google Scholar 

  6. Galli L, Salpietro S, Pellicciotta G, Galliani A, Piatti P, Hasson H, et al. Risk of type 2 diabetes among HIV-infected and healthy subjects in Italy. European journal of epidemiology. 2012;27(8):657–65.

    PubMed  Google Scholar 

  7. Prioreschi A, Munthali RJ, Soepnel L, Goldstein JA, Micklesfield LK, Aronoff DM, et al. Incidence and prevalence of type 2 diabetes mellitus with HIV infection in Africa: a systematic review and meta-analysis. BMJ open. 2017;7(3):e013953.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Butt AA, McGinnis K, Rodriguez-Barradas MC, Crystal S, Simberkoff M, Goetz MB, et al. HIV infection and the risk of diabetes mellitus. Aids. 2009;23(10):1227–34.

    PubMed  PubMed Central  Google Scholar 

  9. Eckard AR, McComsey GA. Weight gain and integrase inhibitors. Curr Opin Infect Dis. 2020;33(1):10–9.

    PubMed  PubMed Central  Google Scholar 

  10. Knudsen AD, Krebs-Demmer L, Bjørge NID, Elming MB, Gelpi M, Sigvardsen PE, et al. Pericardial adipose tissue volume is independently associated with human immunodeficiency virus status and prior use of stavudine, didanosine, or indinavir. The Journal of infectious diseases. 2020;222(1):54–61.

    CAS  PubMed  Google Scholar 

  11. Antonopoulos AS, Antoniades C. The role of epicardial adipose tissue in cardiac biology: classic concepts and emerging roles. The Journal of physiology. 2017;595(12):3907–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 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.

    CAS  PubMed  Google Scholar 

  13. Mallon PW, Miller J, Cooper DA, Carr A. Prospective evaluation of the effects of antiretroviral therapy on body composition in HIV-1-infected men starting therapy. Aids. 2003;17(7):971–9.

    CAS  PubMed  Google Scholar 

  14. https://clinicalinfo.hiv.gov/sites/default/files/inline-files/AdultandAdolescentGL.pdf. Accessed (October 3, 2020). PoAGfAaAGftUoAAiAaAwHDoHaHSAa.

  15. Sax PE, Erlandson KM, Lake JE, Mccomsey GA, Orkin C, Esser S, et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020;71(6):1379–89.

    CAS  Google Scholar 

  16. Venter WDF, Moorhouse M, Sokhela S, Fairlie L, Mashabane N, Masenya M, et al. Dolutegravir plus two different prodrugs of tenofovir to treat HIV. New Engl J Med. 2019;381(9):803–15.

    CAS  PubMed  Google Scholar 

  17. Kim PS, Woods C, Georgoff P, Crum D, Rosenberg A, Smith M, et al. A1C underestimates glycemia in HIV infection. Diabetes Care. 2009;32(9):1591–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Assoc AD. Classification and diagnosis of diabetes: standards of medical care in diabetes-2020. Diabetes Care. 2020;43:S14–31.

    Google Scholar 

  19. Garber AJ, Handelsman Y, Grunberger G, Einhorn D, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm-2020 executive summary. Endocr Pract. 2020;26(1):107–39.

    PubMed  Google Scholar 

  20. 5. Facilitating behavior change and well-being to improve health outcomes: standards of medical care in diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S48-s65.

  21. Weiss JJ, Sanchez L, Hubbard J, Lo J, Grinspoon SK, Fitch KV. Diet quality is low and differs by sex in people with HIV. The Journal of nutrition. 2019;149(1):78–87.

    PubMed  PubMed Central  Google Scholar 

  22. Arnett DK, Khera A, Blumenthal RS. 2019 ACC/AHA Guideline on the primary prevention of cardiovascular disease: Part 1, Lifestyle and behavioral factors. Jama Cardiol. 2019;4(10):1043–4.

    PubMed  Google Scholar 

  23. Schuelter-Trevisol F, Wolff FH, Alencastro PR, et al. Physical activity: do patients infected with HIV practice? How much? A systematic review. Current HIV research. 2012;10(6):487–97.

    CAS  PubMed  Google Scholar 

  24. Vancampfort D, Mugisha J, Richards J, De Hert M, Probst M, Stubbs B. Physical activity correlates in people living with HIV/AIDS: a systematic review of 45 studies. Disability and rehabilitation. 2018;40(14):1618–29.

    PubMed  Google Scholar 

  25. Assoc AD. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2020 (vol 43, pg S98, 2020). Diabetes Care. 2020;43(8):1979.

    Google Scholar 

  26. Custodio J, West S, Yu A, Martin H, Graham H, Quirk E, et al. Lack of clinically relevant effect of bictegravir (BIC, B) on metformin (MET) pharmacokinetics (PK) and pharmacodynamics (PD). Open forum infectious diseases. 2017;4(Suppl 1):S429.

    PubMed Central  Google Scholar 

  27. Han JH, Gordon K, Womack JA, Gibert CL, Leaf DA, Rimland D, et al. Comparative effectiveness of diabetic oral medications among HIV-infected and HIV-uninfected veterans. Diabetes Care. 2017;40(2):218–25.

    CAS  PubMed  Google Scholar 

  28. Sherifali D, Nerenberg K, Pullenayegum E, Cheng JE, Gerstein HC. The effect of oral antidiabetic agents on A1C levels: a systematic review and meta-analysis. Diabetes Care. 2010;33(8):1859–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Viscoli CM, Inzucchi SE, Young LH, Insogna KL, Conwit R, Furie KL, et al. Pioglitazone and risk for bone fracture: safety data from a randomized clinical trial. The Journal of clinical endocrinology and metabolism. 2017;102(3):914–22.

    PubMed  Google Scholar 

  30. Schwartz AV, Sellmeyer DE, Vittinghoff E, Palermo L, Lecka-Czernik B, Feingold KR, et al. Thiazolidinedione use and bone loss in older diabetic adults. The Journal of clinical endocrinology and metabolism. 2006;91(9):3349–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Ferwana M, Firwana B, Hasan R, al-Mallah MH, Kim S, Montori VM, et al. Pioglitazone and risk of bladder cancer: a meta-analysis of controlled studies. Diabetic medicine : a journal of the British Diabetic Association. 2013;30(9):1026–32.

    CAS  Google Scholar 

  32. Tuccori M, Filion KB, Yin H, Yu OH, Platt RW, Azoulay L. Pioglitazone use and risk of bladder cancer: population based cohort study. BMJ (Clinical research ed). 2016;352:i1541.

    Google Scholar 

  33. Lewis JD, Habel LA, Quesenberry CP, Strom BL, Peng T, Hedderson MM, et al. Pioglitazone use and risk of bladder cancer and other common cancers in persons with diabetes. Jama. 2015;314(3):265–77.

    CAS  PubMed  Google Scholar 

  34. Filipova E, Uzunova K, Kalinov K, Vekov T. Pioglitazone and the risk of bladder cancer: a meta-analysis. Diabetes therapy : research, treatment and education of diabetes and related disorders. 2017;8(4):705–26.

    CAS  Google Scholar 

  35. Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58(4):773–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366(9493):1279–89.

    CAS  Google Scholar 

  37. Maggi P, Di Biagio A, Rusconi S, et al. Cardiovascular risk and dyslipidemia among persons living with HIV: a review. Bmc Infect Dis. 2017;17:551.

    PubMed  PubMed Central  Google Scholar 

  38. Koutkia P, Grinspoon S. HIV-associated lipodystrophy: pathogenesis, prognosis, treatment, and controversies. Annual review of medicine. 2004;55:303–17.

    CAS  PubMed  Google Scholar 

  39. Yarasheski KE, Cade WT, Overton ET, Mondy KE, Hubert S, Laciny E, et al. Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity. American journal of physiology Endocrinology and metabolism. 2011;300(1):E243–51.

    CAS  PubMed  Google Scholar 

  40. Slama L, Lanoy E, Valantin MA, Bastard JP, Chermak A, Boutekatjirt A, et al. Effect of pioglitazone on HIV-1-related lipodystrophy: a randomized double-blind placebo-controlled trial (ANRS 113). Antivir Ther. 2008;13(1):67–76.

    CAS  PubMed  Google Scholar 

  41. Calmy A, Hirschel B, Hans D, Karsegard VL, Meier CA. Glitazones in lipodystrophy syndrome induced by highly active antiretroviral therapy. Aids. 2003;17(5):770–2.

    PubMed  Google Scholar 

  42. Gomez-Peralta F, Abreu C, Gomez-Rodriguez S, Barranco RJ, Umpierrez GE. Safety and efficacy of DPP4 inhibitor and basal insulin in type 2 diabetes: an updated review and challenging clinical scenarios. Diabetes therapy : research, treatment and education of diabetes and related disorders. 2018;9(5):1775–89.

    CAS  Google Scholar 

  43. Hinnen D. Glucagon-like peptide 1 receptor agonists for type 2 diabetes. Diabetes spectrum : a publication of the American Diabetes Association. 2017;30(3):202–10.

    Google Scholar 

  44. Gallwitz B. Clinical use of DPP-4 inhibitors. Frontiers in endocrinology. 2019;10:389.

    PubMed  PubMed Central  Google Scholar 

  45. Onglyza (saxagliptin) - FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022350lbl.pdf. Accessed November 30.

  46. Lambeir AM, Durinx C, Scharpé S, De Meester I. Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Critical reviews in clinical laboratory sciences. 2003;40(3):209–94.

    CAS  PubMed  Google Scholar 

  47. 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. The Journal of clinical endocrinology and metabolism. 2013;98(2):743–51.

    CAS  PubMed  Google Scholar 

  48. Makdissi A, Ghanim H, Vora M, Green K, Abuaysheh S, Chaudhuri A, et al. Sitagliptin exerts an antinflammatory action. The Journal of clinical endocrinology and metabolism. 2012;97(9):3333–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Tremblay AJ, Lamarche B, Deacon CF, Weisnagel SJ, Couture P. Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes. Metabolism: clinical and experimental. 2014;63(9):1141–8.

    CAS  Google Scholar 

  50. Dube MP, Chan ES, Lake JE, et al. A randomized, double-blinded, placebo-controlled trial of sitagliptin for reducing inflammation and immune activation in treated and suppressed human immunodeficiency virus infection. Clinical Infectious Diseases. 2019;69(7):1165–72.

    CAS  PubMed  Google Scholar 

  51. Aroda VR. A review of GLP-1 receptor agonists: evolution and advancement, through the lens of randomised controlled trials. Diabetes, obesity & metabolism. 2018;20(Suppl 1):22–33.

    CAS  Google Scholar 

  52. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 2016;375(4):311–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. The New England journal of medicine. 2016;375(19):1834–44.

    CAS  PubMed  Google Scholar 

  54. Diamant M, van Agtmael M. Liraglutide treatment in a patient with HIV and uncontrolled insulin-treated type 2 diabetes. Diabetes Care. 2012;35(5):e34.

    PubMed  PubMed Central  Google Scholar 

  55. García de Lucas MD, Olalla Sierra J, Piña Fernández J. Liraglutide treatment in a patient with HIV, type 2 diabetes and sleep apnoea-hypopnoea syndrome. Diabetes & metabolism. 2015;41(1):102–3.

    Google Scholar 

  56. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. The New England journal of medicine. 2015;373(22):2117–28.

    CAS  PubMed  Google Scholar 

  57. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine. 2019;380(4):347–57.

    CAS  PubMed  Google Scholar 

  58. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. The New England journal of medicine. 2017;377(7):644–57.

    CAS  PubMed  Google Scholar 

  59. Das SR, Everett BM, Birtcher KK, Brown JM, Januzzi JL Jr, Kalyani RR, et al. 2020 expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2020;76(9):1117–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. The New England journal of medicine. 2019;380(24):2295–306.

    CAS  PubMed  Google Scholar 

  61. García de Lucas MD, Olalla J. Experience of using ISGTL-2 in patients with DM2 and HIV infection. European journal of internal medicine. 2017;41:e29.

    PubMed  Google Scholar 

  62. Kaarsholm NC, Lin S, Yan L, Kelly T, van Heek M, Mu J, et al. Engineering glucose responsiveness into insulin. Diabetes. 2018;67(2):299–308.

    CAS  PubMed  Google Scholar 

  63. Garber AJ, Handelsman Y, Grunberger G, Einhorn D, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2020 executive summary. Endocr Pract. 2020;26(1):107–39.

    PubMed  Google Scholar 

  64. Kaku M, Simpson DM. HIV neuropathy. Curr Opin Hiv Aids. 2014;9(6):521–6.

    CAS  PubMed  Google Scholar 

  65. Assoc AD. Microvascular complications and foot care: standards of medical care in diabetes-2020. Diabetes Care. 2020;43:S135–51.

    Google Scholar 

  66. "Burden of Vision Loss." https://www.cdc.gov/visionhealth/risk/burden.htm. Accessed October 2.

  67. Skiest DJ. Cytomegalovirus retinitis in the era of highly active antiretroviral therapy (HAART). Am J Med Sci. 1999;317(5):318–35.

    CAS  PubMed  Google Scholar 

  68. Goldberg DE, Smithen LM, Angelilli A, Freeman WR. HIV-associated retinopathy in the HAART era. Retina-J Ret Vit Dis. 2005;25(5):633–49.

    Google Scholar 

  69. Umanath K, Lewis JB. Update on diabetic nephropathy: core curriculum 2018. Am J Kidney Dis. 2018;71(6):884–95.

    PubMed  Google Scholar 

  70. Cohen SD, Kopp JB, Kimmel PL. Kidney diseases associated with human immunodeficiency virus infection. New Engl J Med. 2017;377(24):2363–74.

    CAS  PubMed  Google Scholar 

  71. Palella FJ Jr, Li X, Gupta SK, et al. Long-term kidney function, proteinuria, and associated risks among HIV-infected and uninfected men. Aids. 2018;32(10):1247–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 10. Cardiovascular disease and risk management: standards of medical care in diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S111-s134.

  73. Grinspoon SK, Fitch KV, Overton ET, Fichtenbaum CJ, Zanni MV, Aberg JA, et al. Rationale and design of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE). Am Heart J. 2019;212:23–35.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sudipa Sarkar.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Pharmacologic Treatment of Type 2 Diabetes

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sarkar, S., Brown, T.T. Diabetes in People with HIV. Curr Diab Rep 21, 13 (2021). https://doi.org/10.1007/s11892-021-01382-8

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11892-021-01382-8

Keywords

  • HIV
  • Antiretroviral therapy
  • Diabetes
  • Microvascular complications
  • Macrovascular complications