The Cause-and-Effect Link Between HIV and Diabetes

Both HIV and HIV-Associated Drug Therapies Shown to Increase Risk

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Type 2 diabetes is often associated with long-term HIV infection, the cause of which has been linked in the past to use of certain antiretroviral drugs (ARVs)—particularly "older" protease inhibitor-class drugs like Crixivan (indinavir) and full strength Norvir (ritonavir).

While is not entirely clear how much ARVs contribute, we do know is that diabetes risk for a person living with HIV is most often based on a number of contributing factors, including:

In recent years, however, research has suggested that both chronic inflammation associated with long-term infection and chronic therapies used to treat HIV-associated conditions may, in fact, increase diabetes risk significantly.

Diabetes and HIV-Associated Chronic Inflammation

Even when HIV is dormant or is fully suppressed by means of antiretroviral therapy (ART), the presence of the latent virus results in an on-ongoing inflammatory response as the body's immune system is left on high alert.

During HIV-associated chronic inflammation, certain inflammatory markers—called C-reactive protein (CRP) and interleukin-6 (IL-6)—are known to increase. Recent research suggests that rises in these markers significantly increase the likelihood in diabetes in people on ART.

Scientists with the INSIGHT SMART and ESPIRIT study groups investigated the diabetes incidence among 3,695 HIV-positive patients on ART over an average of 4.6 years. Average CD4 count among the participant was considered high at 523 cell/mL.   

Based on the data, patients with higher CRP and IL-6 were more likely to develop type 2 diabetes, with a doubling of the CRP and IL-6 from the baseline resulting in a 20% and 33% greater risk, respectively.

All told, 137 people developed diabetes during the course of the trial at a rate of 8.18 per 1,000-patient years.

While traditional co-factors were seen to contribute to the development of diabetes among study participants—including high body mass index (BMI), older age, hepatitis coinfection and statin drugs—the fact that even low-grade inflammation could contribute was regarded as significant, providing a framework by which to better identify individuals at high risk for type 2 diabetes and to ensure appropriate interventions before the start of ART.

Diabetes Linked to Statin Drug Use?

One of the conundrums of preventing diabetes in people with HIV is the impact of statin drugs on disease development. The drugs, used to treat high lipids (particularly high LDL cholesterol), are considered vital in avoiding cardiovascular disease in a population where the likelihood of heart attacks is nearly double that of the general population.

However, new research from on-going HIV Outpatient Study (HOPS) has shown that use of statin drugs in people with HIV can increase the risk of diabetes by some 10% with every year of use.

The 10-year observational analysis, which followed 4,962 HIV-positive patients from 2002 to 2011, looked into the incidence of type 2 diabetes among individuals given statin drugs (590) versus those who were not (4,372).

Adjusting the model for age, sex, ethnicity, ARV use and BMI, the investigators were able to conclude that the risk of diabetes increased steadily the longer the statin exposure.

However, they were also quick to note that the increases were also directly linked to older age and a higher BMI, as well as to race/ethnicity (with 50% higher rates among blacks and more the double among Hispanics). Unsurprisingly, few cases were reported among younger patients, while the impact of protease inhibitors was seen to be statistically insignificant.

From an advisory standpoint, the HOPS researchers strongly advised that statin "not be avoided if clinically indicated" due to their "demonstrated benefits for cardiovascular disease prevention."

So while statin drugs remain vital as a means to lower lipids in people with HIV, they should not be used in isolation. To truly reduce risk requires an holistic approach, including a reduced fat diet, regular exercise, smoking cessation, and the timely initiation of ART with optimal adherence to ensure viral suppression (to better minimize the inflammatory response of untreated HIV disease).

Sources:

Béténé A Dooko, C.;  De Wit, S.; Neuhaus, J.; et al. "Interleukin-6, High Sensitivity C-Reactive Protein, and the Development of Type 2 Diabetes Among HIV-Positive Patients Taking Antiretroviral Therapy." Journal of Acquired Immune Deficiency Syndromes. December 15, 2014; 67(5):538-546.

Lichtenstein K.; Debes, R.; Wood, K. et al. "Statin use is associated with incident diabetes mellitus among patients in the HIV Outpatient Study." 20th Conference on Retroviruses and Opportunistic Infections (CROI). March 3-6, 2013; Atlanta, Georgia; abstract 767.

Freiberg, M.; Chang, C.; Kuller, L.; et al. "HIV infection and the risk of acute myocardial infarction."  Journal of the American Medical Association (JAMA) Internal Medicine. April 22, 2013; 173(8):614-622.

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