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Diabetes – Causes


Type 2 diabetes mellitus is caused by dysregulation at multiple organ sites including insulin resistance in muscle and adipose tissue, a progressive decline in insulin secretion by the pancreas, excess glucose production by the liver and other hormonal deficiencies that together produce a combination of complex metabolic disorders.1 

Abnormal glucose homeostasis and diabetes may be associated with dyslipidemia and increased cardiovascular risk.1–3

Antiretrovirals and other medications

  • The use of some PIs, such as indinavir and lopinavir/ritonavir, has been associated with increased insulin resistance4,5
    • the mechanism for insulin resistance in patients receiving PIs may involve interference with glucose transport through inhibition of a molecule known as GLUT4 (glucose transporter type 4).6,7 
  • In addition, the use of the nucleoside reverse transcriptase inhibitors (NRTIs) didanosine, stavudine and zidovudine has been associated with increased insulin resistance and diabetes.5,8 
  • Elevated inflammatory markers following initiation of antiretroviral therapy have been associated with increased risk of diabetes.9
  • Use of some drugs may also increase the risk of diabetes, including some antihypertensives10 and some neuroleptic drugs.11


  1. Rodbard HW, Blonde L, Braithwaite SS, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007;13(Suppl 1):1–68. 
  2. American Diabetes Association. Standards of Medical Care in Diabetes 2011. Diabetes Care. 2011;34;Suppl 1:S11–S61.
  3. International Diabetes Federation. Global Guideline for Type 2 Diabetes, 2005. Accessed 20 February 2011. 
  4. Noor MA, Seneviratne T, Aweeka FT, et al. Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: a randomized, placebo-controlled study. AIDS. 2002;16:F1–8. 
  5. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Department of Health and Human Services, 2011. Accessed 18 March 2011. 
  6. Hertel J, Struthers H, Horj CB, et al. A structural basis for the acute effects of HIV protease inhibitors on GLUT4 intrinsic activity. J Biol Chem. 2004;279:55147–55152. 
  7. Vyas AK, Koster JC, Tzekov A, et al. Effects of the HIV protease inhibitor ritonavir on GLUT4 knock-out mice. J Biol Chem. 2010;285:36395–36400. 
  8. De Wit S, Sabin CA, Weber R, 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;31:1224–1229.
  9. Brown TT, Tassiopoulos K, Bosch RJ, et al. Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy. Diabetes Care. 2010;33:2244–2249. 
  10. Elliott WJ, Mayer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007 20;369(9557):201-207.
  11. Sernyak MJ, Leslie DL, Alarcon RD, et al. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry. 2002;159(4):561-566.