Dissecting the interaction between antiviral medication and diabetes mellitus
Abstract
Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose levels (hyperglycemia) due to defects in insulin secretion, insulin action, or both. Infectious diseases by various viruses can impact humans’ health. It has been demonstrated that antiviral medications may be linked to the development of diabetes or exacerbation of existing diabetes mellitus. This mini review aims to summarize the current evidence on the effects of antiviral agents on blood glucose levels. The studies revealed that some antiviral drugs, such as Ribavirin, Remdesivir, Interferon-α, Lopinavir, Ritonavir, and Zidovudine, have the potential to increase the risk of development of diabetes mellitus or worsen existing diabetes. While Raltegravir's impact on diabetes mellitus is controversial. Therefore, it can be suggested the measurement of blood glucose, insulin, glutamic acid decarboxylase and islet cell autoantibody levels before and during the antiviral therapy.
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2. Krause M, De Vito G. Type 1 and Type 2 Diabetes Mellitus: Commonalities, Differences and the Importance of Exercise and Nutrition. Nutrients. 2023;15(19).
3. Nomiyama T, Yanase T. [Secondary diabetes]. Nihon Rinsho. 2015;73(12):2008-12.
4. Kumar A, Gangwar R, Zargar AA, Kumar R, Sharma A. Prevalence of Diabetes in India: A Review of IDF Diabetes Atlas 10th Edition. Curr Diabetes Rev. 2024;20(1):e130423215752.
5. Xu G, Liu B, Sun Y, Du Y, Snetselaar LG, Hu FB, et al. Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: population based study. Bmj. 2018;362:k1497.
6. Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of Type 2 Diabetes - Global Burden of Disease and Forecasted Trends. J Epidemiol Glob Health. 2020;10(1):107-11.
7. Woolhouse M, Scott F, Hudson Z, Howey R, Chase-Topping M. Human viruses: discovery and emergence. Philos Trans R Soc Lond B Biol Sci. 2012;367(1604):2864-71.
8. Kausar S, Said Khan F, Ishaq Mujeeb Ur Rehman M, Akram M, Riaz M, Rasool G, et al. A review: Mechanism of action of antiviral drugs. Int J Immunopathol Pharmacol. 2021;35:20587384211002621.
9. White DL, Ratziu V, El-Serag HB. Hepatitis C infection and risk of diabetes: a systematic review and meta-analysis. Journal of hepatology. 2008;49(5):831-44.
10. Oka R, Hiroi N, Shigemitsu R, Sue M, Oshima Y, Yoshida-Hiroi M. Type 1 Diabetes Mellitus Associated with Pegylated Interferon-α Plus Ribavirin Treatment for Chronic Hepatitis C: Case Report and Literature Review. Clin Med Insights Endocrinol Diabetes. 2011;4:39-45.
11. Te HS, Randall G, Jensen DM. Mechanism of action of ribavirin in the treatment of chronic hepatitis C. Gastroenterol Hepatol (N Y). 2007;3(3):218-25.
12. Loustaud-Ratti V, Debette-Gratien M, Jacques J, Alain S, Marquet P, Sautereau D, et al. Ribavirin: Past, present and future. World J Hepatol. 2016;8(2):123-30.
13. Ando K, Kim SR, Imoto S, Nakajima T, Mita K, Fukuda K, et al. Acute pancreatitis associated with pegylated interferon and ribavirin treatment of chronic hepatitis C, genotype 1b with high viral load. Case reports in gastroenterology. 2009;3(3):372-6.
14. Cozzolongo R, Betterle C, Fabris P, Paola Albergoni M, Lanzilotta E, Manghisi OG. Onset of type 1 diabetes mellitus during peginterferon alpha-2b plus ribavirin treatment for chronic hepatitis C. Eur J Gastroenterol Hepatol. 2006;18(6):689-92.
15. Schreuder TC, Gelderblom HC, Weegink CJ, Hamann D, Reesink HW, Devries JH, et al. High incidence of type 1 diabetes mellitus during or shortly after treatment with pegylated interferon alpha for chronic hepatitis C virus infection. Liver Int. 2008;28(1):39-46.
16. Mohammadi H, Shooraj M, Ehteshaminia Y, Mahdavi SA. A Review on the Co-infection of HIV and Parasitic Diseases. Tabari Biomedical Student Research Journal. 2022;4(1):23-9.
17. Loos NH, Beijnen JH, Schinkel AH. The mechanism-based inactivation of CYP3A4 by ritonavir: what mechanism? International Journal of Molecular Sciences. 2022;23(17):9866.
18. Ismail W, King J, Pillay T. Insulin resistance induced by antiretroviral drugs: Current understanding of molecular mechanisms. Journal of Endocrinology, Metabolism and Diabetes of South Africa. 2009;14(3):129-32.
19. Carper MJ, Cade WT, Cam M, Zhang S, Shalev A, Yarasheski KE, et al. HIV-protease inhibitors induce expression of suppressor of cytokine signaling-1 in insulin-sensitive tissues and promote insulin resistance and type 2 diabetes mellitus. American Journal of Physiology-Endocrinology And Metabolism. 2008;294(3):E558-E67.
20. Vyas AK, Koster JC, Tzekov A, Hruz PW. Effects of the HIV protease inhibitor ritonavir on GLUT4 knock-out mice. Journal of Biological Chemistry. 2010;285(47):36395-400.
21. Dejkhamron P, Unachak K, Aurpibul L, Sirisanthana V. Insulin resistance and lipid profiles in HIV-infected Thai children receiving lopinavir/ritonavir-based highly active antiretroviral therapy. J Pediatr Endocrinol Metab. 2014;27(5-6):403-12.
22. Oldfield V, Plosker GL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs. 2006;66:1275-99.
23. Cvetkovic RS, Goa KL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs. 2003;63(8):769-802.
24. Djedaini M, Peraldi P, Drici M-D, Darini C, Saint-Marc P, Dani C, et al. Lopinavir co-induces insulin resistance and ER stress in human adipocytes. Biochemical and biophysical research communications. 2009;386(1):96-100.
25. Kitazawa T, Yoshino Y, Suzuki S, Koga I, Ota Y. Lopinavir inhibits insulin signaling by promoting protein tyrosine phosphatase 1B expression. Experimental and therapeutic medicine. 2014;8(3):851-5.
26. Noor MA, Parker RA, O'Mara E, Grasela DM, Currie A, Hodder SL, et al. The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults. Aids. 2004;18(16):2137-44.
27. Lee GA, Rao M, Mulligan K, Lo JC, Aweeka F, Schwarz J-M, et al. Effects of ritonavir and amprenavir on insulin sensitivity in healthy volunteers. Aids. 2007;21(16):2183-90.
28. Lee GA, Lo JC, Aweeka F, Schwarz JM, Mulligan K, Schambelan M, et al. Single-dose lopinavir-ritonavir acutely inhibits insulin-mediated glucose disposal in healthy volunteers. Clin Infect Dis. 2006;43(5):658-60.
29. Mohammadi H, Ehteshaminia Y, Mahdavi SA. A Review on Prevention, Transmission and Symptoms of the COVID-19. Tabari Biomedical Student Research Journal. 2020.
30. Saha A, Sharma AR, Bhattacharya M, Sharma G, Lee S-S, Chakraborty C. Probable molecular mechanism of remdesivir for the treatment of COVID-19: need to know more. Archives of Medical research. 2020;51(6):585-6.
31. Parise R, Deruiter J, Ren J, Govindarajulu M, Ramesh S, Nadar RM, et al. Impact of COVID-19 therapy on hyperglycemia. SAGE Publications Sage UK: London, England; 2022. p. 14791641221095091.
32. Kim W, Lee GW, Rhee N, Min KH, Kim JH, Gil JY, et al. Risk factors for hyperglycemia in COVID‐19 patients treated with remdesivir. Clinical and Translational Science. 2024;17(1):e13684.
33. Gandham R, Eerike M, Raj GM, Bisoi D, Priyadarshini R, Agarwal N. Adverse events following remdesivir administration in moderately ill COVID-19 patients-A retrospective analysis. Journal of family medicine and primary care. 2022;11(7):3693-8.
34. Majewska A, Mlynarczyk-Bonikowska B. 40 years after the registration of acyclovir: do we need new anti-herpetic drugs? International journal of molecular sciences. 2022;23(7):3431.
35. Hu Z, Zhou J, Han L, Li X, Li C, Wu T, et al. Acyclovir alleviates insulin resistance via activating PKM1 in diabetic mice. Life Sciences. 2022;304:120725.
36. Sagawa N, Tsurutani Y, Nomura K, Okuyama T, Kondo M, Sata A, et al. [Acyclovir-induced neurotoxicity and acute kidney injury in an elderly diabetic patient treated with valacyclovir: report of a case]. Nihon Ronen Igakkai Zasshi. 2014;51(6):581-5.
37. Guo J-T, Sohn JA, Zhu Q, Seeger C. Mechanism of the interferon alpha response against hepatitis C virus replicons. Virology. 2004;325(1):71-81.
38. Li Q, Xu B, Michie SA, Rubins KH, Schreriber RD, McDevitt HO. Interferon-alpha initiates type 1 diabetes in nonobese diabetic mice. Proc Natl Acad Sci U S A. 2008;105(34):12439-44.
39. Devendra D, Eisenbarth G. Interferon alpha—a potential link in the pathogenesis of viral-induced type 1 diabetes and autoimmunity. Clinical immunology. 2004;111(3):225-33.
40. Fabris P, Floreani A, Tositti G, Vergani D, De Lalla F, Betterle C. Type 1 diabetes mellitus in patients with chronic hepatitis C before and after interferon therapy. Aliment Pharmacol Ther. 2003;18(6):549-58.
41. Piquer S, Hernández C, Enriquez J, Ross A, Esteban JI, Genescà J, et al. Islet cell and thyroid antibody prevalence in patients with hepatitis C virus infection: effect of treatment with interferon. J Lab Clin Med. 2001;137(1):38-42.
42. Tanaka J, Sugimoto K, Shiraki K, Beppu T, Yoneda K, Fuke H, et al. Type 1 diabetes mellitus provoked by peginterferon α-2b plus ribavirin treatment for chronic hepatitis C. Internal Medicine. 2008;47(8):747-9.
43. Temesgen Z, Siraj DS. Raltegravir: first in class HIV integrase inhibitor. Ther Clin Risk Manag. 2008;4(2):493-500.
44. Dirajlal-Fargo S, Moser C, Brown TT, Kelesidis T, Dube MP, Stein JH, et al. Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s. Open Forum Infect Dis. 2016;3(3):ofw174.
45. Kajogoo VD, Amogne W, Medhin G. New onset type 2 diabetes mellitus risks with integrase strand transfer inhibitors-based regimens: A systematic review and meta-analysis. Metabol Open. 2023;17:100235.
46. Ghodke Y, Anderson PL, Sangkuhl K, Lamba J, Altman RB, Klein TE. PharmGKB summary: zidovudine pathway. Pharmacogenet Genomics. 2012;22(12):891-4.
47. Iwata K, Ogawa W. Reversible diabetes mellitus induced by use of, and improved after discontinuation of, the antiretroviral medication zidovudine: a case report. J Med Case Rep. 2017;11(1):157.
48. Blümer RM, van Vonderen MG, Sutinen J, Hassink E, Ackermans M, van Agtmael MA, et al. Zidovudine/lamivudine contributes to insulin resistance within 3 months of starting combination antiretroviral therapy. Aids. 2008;22(2):227-36.
49. Karamchand S, Leisegang R, Schomaker M, Maartens G, Walters L, Hislop M, et al. Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy. Medicine. 2016;95(9):e2844.
50. Faizal S, Marianne H, Cathy MP, Monica Y, Jason C, Sarah C, et al. Incidence of diabetes mellitus and factors associated with its development in HIV-positive patients over the age of 50. BMJ Open Diabetes Research & Care. 2017;5(1):e000457.
2. Krause M, De Vito G. Type 1 and Type 2 Diabetes Mellitus: Commonalities, Differences and the Importance of Exercise and Nutrition. Nutrients. 2023;15(19).
3. Nomiyama T, Yanase T. [Secondary diabetes]. Nihon Rinsho. 2015;73(12):2008-12.
4. Kumar A, Gangwar R, Zargar AA, Kumar R, Sharma A. Prevalence of Diabetes in India: A Review of IDF Diabetes Atlas 10th Edition. Curr Diabetes Rev. 2024;20(1):e130423215752.
5. Xu G, Liu B, Sun Y, Du Y, Snetselaar LG, Hu FB, et al. Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: population based study. Bmj. 2018;362:k1497.
6. Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of Type 2 Diabetes - Global Burden of Disease and Forecasted Trends. J Epidemiol Glob Health. 2020;10(1):107-11.
7. Woolhouse M, Scott F, Hudson Z, Howey R, Chase-Topping M. Human viruses: discovery and emergence. Philos Trans R Soc Lond B Biol Sci. 2012;367(1604):2864-71.
8. Kausar S, Said Khan F, Ishaq Mujeeb Ur Rehman M, Akram M, Riaz M, Rasool G, et al. A review: Mechanism of action of antiviral drugs. Int J Immunopathol Pharmacol. 2021;35:20587384211002621.
9. White DL, Ratziu V, El-Serag HB. Hepatitis C infection and risk of diabetes: a systematic review and meta-analysis. Journal of hepatology. 2008;49(5):831-44.
10. Oka R, Hiroi N, Shigemitsu R, Sue M, Oshima Y, Yoshida-Hiroi M. Type 1 Diabetes Mellitus Associated with Pegylated Interferon-α Plus Ribavirin Treatment for Chronic Hepatitis C: Case Report and Literature Review. Clin Med Insights Endocrinol Diabetes. 2011;4:39-45.
11. Te HS, Randall G, Jensen DM. Mechanism of action of ribavirin in the treatment of chronic hepatitis C. Gastroenterol Hepatol (N Y). 2007;3(3):218-25.
12. Loustaud-Ratti V, Debette-Gratien M, Jacques J, Alain S, Marquet P, Sautereau D, et al. Ribavirin: Past, present and future. World J Hepatol. 2016;8(2):123-30.
13. Ando K, Kim SR, Imoto S, Nakajima T, Mita K, Fukuda K, et al. Acute pancreatitis associated with pegylated interferon and ribavirin treatment of chronic hepatitis C, genotype 1b with high viral load. Case reports in gastroenterology. 2009;3(3):372-6.
14. Cozzolongo R, Betterle C, Fabris P, Paola Albergoni M, Lanzilotta E, Manghisi OG. Onset of type 1 diabetes mellitus during peginterferon alpha-2b plus ribavirin treatment for chronic hepatitis C. Eur J Gastroenterol Hepatol. 2006;18(6):689-92.
15. Schreuder TC, Gelderblom HC, Weegink CJ, Hamann D, Reesink HW, Devries JH, et al. High incidence of type 1 diabetes mellitus during or shortly after treatment with pegylated interferon alpha for chronic hepatitis C virus infection. Liver Int. 2008;28(1):39-46.
16. Mohammadi H, Shooraj M, Ehteshaminia Y, Mahdavi SA. A Review on the Co-infection of HIV and Parasitic Diseases. Tabari Biomedical Student Research Journal. 2022;4(1):23-9.
17. Loos NH, Beijnen JH, Schinkel AH. The mechanism-based inactivation of CYP3A4 by ritonavir: what mechanism? International Journal of Molecular Sciences. 2022;23(17):9866.
18. Ismail W, King J, Pillay T. Insulin resistance induced by antiretroviral drugs: Current understanding of molecular mechanisms. Journal of Endocrinology, Metabolism and Diabetes of South Africa. 2009;14(3):129-32.
19. Carper MJ, Cade WT, Cam M, Zhang S, Shalev A, Yarasheski KE, et al. HIV-protease inhibitors induce expression of suppressor of cytokine signaling-1 in insulin-sensitive tissues and promote insulin resistance and type 2 diabetes mellitus. American Journal of Physiology-Endocrinology And Metabolism. 2008;294(3):E558-E67.
20. Vyas AK, Koster JC, Tzekov A, Hruz PW. Effects of the HIV protease inhibitor ritonavir on GLUT4 knock-out mice. Journal of Biological Chemistry. 2010;285(47):36395-400.
21. Dejkhamron P, Unachak K, Aurpibul L, Sirisanthana V. Insulin resistance and lipid profiles in HIV-infected Thai children receiving lopinavir/ritonavir-based highly active antiretroviral therapy. J Pediatr Endocrinol Metab. 2014;27(5-6):403-12.
22. Oldfield V, Plosker GL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs. 2006;66:1275-99.
23. Cvetkovic RS, Goa KL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs. 2003;63(8):769-802.
24. Djedaini M, Peraldi P, Drici M-D, Darini C, Saint-Marc P, Dani C, et al. Lopinavir co-induces insulin resistance and ER stress in human adipocytes. Biochemical and biophysical research communications. 2009;386(1):96-100.
25. Kitazawa T, Yoshino Y, Suzuki S, Koga I, Ota Y. Lopinavir inhibits insulin signaling by promoting protein tyrosine phosphatase 1B expression. Experimental and therapeutic medicine. 2014;8(3):851-5.
26. Noor MA, Parker RA, O'Mara E, Grasela DM, Currie A, Hodder SL, et al. The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults. Aids. 2004;18(16):2137-44.
27. Lee GA, Rao M, Mulligan K, Lo JC, Aweeka F, Schwarz J-M, et al. Effects of ritonavir and amprenavir on insulin sensitivity in healthy volunteers. Aids. 2007;21(16):2183-90.
28. Lee GA, Lo JC, Aweeka F, Schwarz JM, Mulligan K, Schambelan M, et al. Single-dose lopinavir-ritonavir acutely inhibits insulin-mediated glucose disposal in healthy volunteers. Clin Infect Dis. 2006;43(5):658-60.
29. Mohammadi H, Ehteshaminia Y, Mahdavi SA. A Review on Prevention, Transmission and Symptoms of the COVID-19. Tabari Biomedical Student Research Journal. 2020.
30. Saha A, Sharma AR, Bhattacharya M, Sharma G, Lee S-S, Chakraborty C. Probable molecular mechanism of remdesivir for the treatment of COVID-19: need to know more. Archives of Medical research. 2020;51(6):585-6.
31. Parise R, Deruiter J, Ren J, Govindarajulu M, Ramesh S, Nadar RM, et al. Impact of COVID-19 therapy on hyperglycemia. SAGE Publications Sage UK: London, England; 2022. p. 14791641221095091.
32. Kim W, Lee GW, Rhee N, Min KH, Kim JH, Gil JY, et al. Risk factors for hyperglycemia in COVID‐19 patients treated with remdesivir. Clinical and Translational Science. 2024;17(1):e13684.
33. Gandham R, Eerike M, Raj GM, Bisoi D, Priyadarshini R, Agarwal N. Adverse events following remdesivir administration in moderately ill COVID-19 patients-A retrospective analysis. Journal of family medicine and primary care. 2022;11(7):3693-8.
34. Majewska A, Mlynarczyk-Bonikowska B. 40 years after the registration of acyclovir: do we need new anti-herpetic drugs? International journal of molecular sciences. 2022;23(7):3431.
35. Hu Z, Zhou J, Han L, Li X, Li C, Wu T, et al. Acyclovir alleviates insulin resistance via activating PKM1 in diabetic mice. Life Sciences. 2022;304:120725.
36. Sagawa N, Tsurutani Y, Nomura K, Okuyama T, Kondo M, Sata A, et al. [Acyclovir-induced neurotoxicity and acute kidney injury in an elderly diabetic patient treated with valacyclovir: report of a case]. Nihon Ronen Igakkai Zasshi. 2014;51(6):581-5.
37. Guo J-T, Sohn JA, Zhu Q, Seeger C. Mechanism of the interferon alpha response against hepatitis C virus replicons. Virology. 2004;325(1):71-81.
38. Li Q, Xu B, Michie SA, Rubins KH, Schreriber RD, McDevitt HO. Interferon-alpha initiates type 1 diabetes in nonobese diabetic mice. Proc Natl Acad Sci U S A. 2008;105(34):12439-44.
39. Devendra D, Eisenbarth G. Interferon alpha—a potential link in the pathogenesis of viral-induced type 1 diabetes and autoimmunity. Clinical immunology. 2004;111(3):225-33.
40. Fabris P, Floreani A, Tositti G, Vergani D, De Lalla F, Betterle C. Type 1 diabetes mellitus in patients with chronic hepatitis C before and after interferon therapy. Aliment Pharmacol Ther. 2003;18(6):549-58.
41. Piquer S, Hernández C, Enriquez J, Ross A, Esteban JI, Genescà J, et al. Islet cell and thyroid antibody prevalence in patients with hepatitis C virus infection: effect of treatment with interferon. J Lab Clin Med. 2001;137(1):38-42.
42. Tanaka J, Sugimoto K, Shiraki K, Beppu T, Yoneda K, Fuke H, et al. Type 1 diabetes mellitus provoked by peginterferon α-2b plus ribavirin treatment for chronic hepatitis C. Internal Medicine. 2008;47(8):747-9.
43. Temesgen Z, Siraj DS. Raltegravir: first in class HIV integrase inhibitor. Ther Clin Risk Manag. 2008;4(2):493-500.
44. Dirajlal-Fargo S, Moser C, Brown TT, Kelesidis T, Dube MP, Stein JH, et al. Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s. Open Forum Infect Dis. 2016;3(3):ofw174.
45. Kajogoo VD, Amogne W, Medhin G. New onset type 2 diabetes mellitus risks with integrase strand transfer inhibitors-based regimens: A systematic review and meta-analysis. Metabol Open. 2023;17:100235.
46. Ghodke Y, Anderson PL, Sangkuhl K, Lamba J, Altman RB, Klein TE. PharmGKB summary: zidovudine pathway. Pharmacogenet Genomics. 2012;22(12):891-4.
47. Iwata K, Ogawa W. Reversible diabetes mellitus induced by use of, and improved after discontinuation of, the antiretroviral medication zidovudine: a case report. J Med Case Rep. 2017;11(1):157.
48. Blümer RM, van Vonderen MG, Sutinen J, Hassink E, Ackermans M, van Agtmael MA, et al. Zidovudine/lamivudine contributes to insulin resistance within 3 months of starting combination antiretroviral therapy. Aids. 2008;22(2):227-36.
49. Karamchand S, Leisegang R, Schomaker M, Maartens G, Walters L, Hislop M, et al. Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy. Medicine. 2016;95(9):e2844.
50. Faizal S, Marianne H, Cathy MP, Monica Y, Jason C, Sarah C, et al. Incidence of diabetes mellitus and factors associated with its development in HIV-positive patients over the age of 50. BMJ Open Diabetes Research & Care. 2017;5(1):e000457.
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| Issue | Vol 2 No 3 (2024) | |
| Section | Review Article(s) | |
| Keywords | ||
| Diabetes mellitus insulin antiviral medication viral medication | ||
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How to Cite
1.
Abedi Firouzjaei G, Gorgani-Firuzjaee S. Dissecting the interaction between antiviral medication and diabetes mellitus. ABI. 2024;2(3):119-124.
