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Danish study looks at HIV and meds for their effect on diabetes risk




 

The pancreas gland, located in the abdomen, makes the hormone insulin, which helps cells absorb sugar circulating in the blood. As people age, they may gain weight and become less active and their bodies may become less sensitive to the effects of insulin. This is called insulin resistance. As insulin resistance increases, the pancreas can compensate by producing higher levels of insulin, and for a time it might overcome some of the effects of insulin resistance. However, after a few years and as weight accumulates in the absence of sufficient exercise, insulin resistance can return or intensify and eventually the pancreas gland is worn out. The result is type 2 diabetes, or diabetes mellitus. The presence of type 2 diabetes increases the risk for cardiovascular disease as well as kidney, nerve and eye damage and appears to weaken the immune system. Also, having uncontrolled type 2 diabetes can affect a person’s memory and ability to think clearly. Type 2 diabetes can be prevented with regular medical monitoring, regular exercise, a healthy diet and prescription medicines.

There have been many studies attempting to explore possible connections between HIV infection, potent treatment for HIV (commonly called ART or HAART) and the development of type 2 diabetes. These studies have sometimes produced conflicting results.

Seeking to provide clear conclusions, Danish doctors conducted a large study, comparing health-related data from nearly 4,000 HIV-positive people collected over the course of about 14 years. They compared this information to that collected from about 14,000 HIV-negative people. They found that, overall, from 1999 onward, HIV-positive people did not have an increased risk for the development of type 2 diabetes. However, exposure to certain anti-HIV drugs was associated with an increased risk for type 2 diabetes, as was aging and increasing relative fatness.

Study details

Researchers reviewed health-related information on Danish adults collected between 1995 and 2010. Each HIV-positive person’s information was compared to data from four HIV-negative Danish people of similar age and gender. Overall, data from 3,540 HIV-positive and 14,160 HIV-negative people were used.

The average profile of participants upon entering the study was as follows:

  • 84% males, 16% females
  • age – 39 years
  • CD4+ count – 300 cells
  • HCV co-infection – 19%

Participants were monitored for about eight years, though some were monitored for up to 15 years.

Results

Overall, the following proportions of people developed diabetes:

  • HIV-positive people – 3%
  • HIV-negative people – 4%

Overall, the risk for developing diabetes was not generally significantly different between those two populations.

Changes before 1999

However, at different periods of time during the study, the risk of HIV-positive people developing type 2 diabetes increased and was greater than that of their HIV-negative counterparts. This was the case before 1996 and also from 1996 through 1998. In this latter period, people with HIV had a twofold increased risk for developing type 2 diabetes.

The reasons for the increased risk were as follows:

In the pre-HAART era, participants were likely losing weight (due to AIDS-related wasting) and were exposed to drugs such as pentamidine, which was used to treat AIDS-related pneumonia. Pentamidine is associated with worsening control of blood sugar.

In the years 1996 through 1998, HAART was introduced, with the following drugs playing a major role:

  • d4T (stavudine, Zerit)
  • ddI (didanosine, Videx)
  • indinavir (Crixivan)

The first two drugs are known to affect the health of the pancreas gland. Indinavir is also known to cause problems with insulin resistance. Exposure to one or more of these drugs, according to the Danish team, may in part explain the increased diabetes risk during these years.

Changes after 1999

However, starting in 1999 and to 2010, the risk for diabetes among HIV-positive people fell and was similar to that of HIV-negative people. This is probably because safer anti-HIV medicines were used. The Danish team noted that none of the following drugs were associated with an increased risk for type 2 diabetes:

Protease inhibitors

  • atazanavir (Reyataz)
  • lopinavir (in Kaletra)
  • nelfinavir (Viracept)
  • ritonavir (Norvir)

Nukes

  • 3TC (lamivudine and in Combivir, Kivexa and Trizivir)
  • AZT (Zidovudine, Retrovir and in Combivir and Trizivir)
  • ABC (abacavir, Ziagen and in Kivexa and Trizivir)
  • TDF (tenofovir, Viread and in Truvada, Atripla, Complera and Stribild)

Note that the researchers did not have sufficient data to assess other HIV drugs that are commonly used today.

Taking HAART for many years did not increase the risk for developing type 2 diabetes.

Strengths and weaknesses

The present study does have some weaknesses—for instance, it did not have data on socio-economic status, intensity and duration of exercise or type of exercise done, whether there was a family history of type 2 diabetes and so on. Also, the proportion of women was not large, though it was reflective of the HIV epidemic in Denmark. However, the present study is relatively large and has reached reasonable conclusions particularly for men, some of which are supported by previous studies.

Bear in mind that had a different study enrolled people of colour (who are generally at greater risk for type 2 diabetes than white people) different conclusions might have been found. In the Danish study, the population was primarily male and people who were mostly infected with HIV through sex.

Indeed, a recent American study found an increased risk for type 2 diabetes among 1,500 HIV-positive women compared to 500 HIV-negative women; many of the women in that study were women of colour. Also, a previous American study found that the use of opiates is linked to an increased risk for the development of type 2 diabetes in women, regardless of infection with HIV or hepatitis C.

—Sean R. Hosein

REFERENCES:

  1. Rasmussen LD, Mathiesen ER, Kronborg G, et al. Risk of Diabetes Mellitus in Persons with and without HIV: A Danish Nationwide Population-Based Cohort Study. PLoS One. 2012;7(9):e44575.
  2. Tien PC, Schneider MF, Cox C, et al. Association of HIV infection with Incident Diabetes Mellitus: Impact of using Hemoglobin A1C as a Criterion for Diabetes. J Acquir Immune Defic Syndr. 2012 Aug 8. [Epub ahead of print]
  3. Howard AA, Hoover DR, Anastos K, et al. The effects of opiate use and hepatitis C virus infection on risk of diabetes mellitus in the Women’s Interagency HIV Study. Journal of Acquired Immune Deficiency Syndromes. 2010 Jun;54(2):152-9.
  4. Cruse B, Cysique LA, Markus R, et al. Cerebrovascular disease in HIV-infected individuals in the era of highly active antiretroviral therapy. Journal of Neurovirology. 2012 Aug;18(4):264-76.
  5. McCutchan JA, Marquie-Beck JA, Fitzsimons CA, et al. Role of obesity, metabolic variables, and diabetes in HIV-associated neurocognitive disorder. Neurology. 2012 Feb 14;78(7):485-92.
  6. Gerena Y, Skolasky RL, Velez JM, et al. Soluble and cell-associated insulin receptor dysfunction correlates with severity of HAND in HIV-infected women. PLoS One. 2012;7(5):e37358.
  7. Nakamoto BK, Jahanshad N, McMurtray A, et al. Cerebrovascular risk factors and brain microstructural abnormalities on diffusion tensor images in HIV-infected individuals. Journal of Neurovirology. 2012 Aug;18(4):303-12.



 


Copyright © 2012 -CATIE News, Publisher. All rights reserved to Treatment Update. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284 CATIE News.

Information in this article was accurate in October 2, 2012. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.