Insulin resistance increases risk of brain impairment for adults with HIV

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Insulin resistance is associated with brain impairment in HIV-positive adults, researchers report in the December 1st edition of the Journal of Acquired Immune Deficiency Syndromes. Factors associated with insulin resistance were high blood pressure, being overweight and non-Caucasian ethnicity, but the investigators found that many HIV-related factors, such as CD4 cell count or the use of antiretroviral therapy were significantly associated with an increased risk of insulin resistance.

Thanks to potent anti-HIV treatment there has been a significant reduction in the amount of illness and death caused by HIV in richer countries since the late 1990s. But researchers have noted that the prevalence of HIV-associated dementia has remained broadly stable since the introduction of effective HIV therapy. It has been suggested that side-effects of some anti-HIV drugs, including mitochondrial toxicity, oxidative stress and diabetes mellitus may be contributing to the continuing increased prevalence of neurocognitive impairment seen in people with HIV and at least partially offsetting the beneficial effects of HIV therapy.

Diabetes mellitus and insulin resistance are both known to be associated with cognitive dysfunction in HIV-negative adults. Studies such as the Multicenter AIDS Cohort Study (MACS) have found significant increases in the diabetes amongst people with HIV since the use of potent HIV therapy became widespread, and some researchers are concerned that this could translate into a longer-term risk of brain impairment as the HIV-positive population ages.

Glossary

insulin

A hormone produced by the pancreas that helps regulate the amount of sugar (glucose) in the blood.

diabetes

A group of diseases characterized by high levels of blood sugar (glucose). Type 1 diabetes occurs when the body fails to produce insulin, which is a hormone that regulates blood sugar. Type 2 diabetes occurs when the body either does not produce enough insulin or does not use insulin normally (insulin resistance). Common symptoms of diabetes include frequent urination, unusual thirst and extreme hunger. Some antiretroviral drugs may increase the risk of type 2 diabetes.

dementia

Loss of the ability to process, learn, and remember information. Potential causes include alcohol or drug abuse, depression, anxiety, vascular cognitive impairment, Alzheimer’s disease and HIV-associated neurocognitive disorder (HAND). 

traditional risk factors

Risk factors for a disease which are well established from studies in the general population. For example, traditional risk factors for heart disease include older age, smoking, high blood pressure, cholesterol and diabetes. ‘Traditional’ risk factors may be contrasted with novel or HIV-related risk factors.

high blood pressure

When blood pressure (the force of blood pushing against the arteries) is consistently too high. Raises the risk of heart disease, stroke, kidney failure, cognitive impairment, sight problems and erectile dysfunction.

Investigators from the Hawaii Aging with HIV Cohort hypothesised that increased insulin resistance would be associated with an increased risk of HIV-associated dementia and reduced performance in neuropsychological tests. They therefore conducted a cross-sectional study involving 145 HIV-positive individuals, 74 of whom were “older” (over 49 years), with the remaining 71 patients aged between 20 and 40.

Blood samples to measure insulin levels were obtained, and HIV-associated variables such as CD4 cell count, viral load and the current use of antiretroviral therapy were also assessed. Patients had cognition tests and their performance was stratified on a three-tier scale (normal, minor impairment, or HIV-associated dementia).

Traditional risk factors including high blood pressure (p

In further analysis, the investigators found a significant relationship between increasing insulin resistance and an increasing level of brain impairment (p = 0.044).

“In this anaylsis, we demonstrated an association between insulin resistance and cognitive dysfunction”, comment the investigators. They believe that “these data suggest new vulnerabilities with important applicability to the growing group of aging HIV patients and merit further investigation.”

References

Valcour VG et al. insulin resistance is associated with cognition among HIV-1-infected patients: the Hawaii Aging with HIV Cohort. J Acquir Immune Defic Syndr 43: 405 – 410, 2006.