It’s Time to Examine the Impact of Genetic Susceptibility on the Incidence of Diabetes among HIV-Infected Individuals

Kyle J. Gaulton and Glen N. Gaulton*

It’s Time to Examine the Impact of Genetic Susceptibility on the Incidence of Diabetes among HIV-Infected Individuals

The remarkable advances in application of anti-retroviral therapy to treat HIV
infection has had a profound impact on the HIV epidemic as well as improved the quality and
longevity of life for those who receive such treatment.

Nonetheless, as individuals receiving ART live longer, they may develop chronic
non-communicable disease at an increased incidence and/or severity when
compared to non-infected and/or untreated individuals.

Prime examples of this include cardiovascular and neurological disease,
as well as metabolic syndrome and diabetes mellitus. Whether these growing disease
burdens are identical in origin and outcome to disease in uninfected individuals,
and whether ART impacts disease incidence and
severity in addition to limiting HIV infection is often poorly distinguished.

The data on type 2 diabetes mellitus (T2DM) provides a welcome case in point for this discussion.

There is now a wealth of data documenting the increased incidence of T2DM in HIVinfected subjects under ART.

While the range of this increase varies by study population, location, and drug therapy, the most comprehensive studies typically show an increase of 2.25- 4.7
fold in the incidence of T2DM in HIV positive subjects on ART at four years after diagnosis
and treatment.

Related studies have more recently tied these effects to an increase in the
prevalence of dyslipidemia and metabolic syndrome, to elevated BMI and hypertension as
opposed to the level of HIV or CD4 count,
and lastly to an increase in the rate of death from
the complications of diabetes

While the impact of HIV infection on T2DM in the absence of ART remains in debate,7
there is ample evidence that various protease inhibitors used for ART cause insulin resistance independent of increases in visceral adipose tissue or lipid and lipoprotein levels.

Thus, multiple factors likely bear on the increase in T2DM seen in HIV infected subjects, especially
when undergoing ART.

Diabetes mellitus is a complex disease, and risk factors such as family history,
genetics, obesity, race/ethnicity, age, and dyslipidemia are all poorly understood in
HIV-infected individuals.

However, remarkable insights into the genetic factors that foster predisposition
to T2DM are rapidly emerging.

These observations illustrate that risk of T2DM is mediated by hundreds of genetic factors,
the majority of which commonly occur in the general population.

HIV/AIDS Res Treat Open J. 2016; 3(1): e1-e2. doi: 10.17140/HARTOJ-3-e008