Diabetes significantly increases HIV-associated dementia risk

HIV-related diabetes significantly increases the risk of HIV-associated dementia, according to a study published in the January 1^st issue of the Journal of AIDS. In addition, the researchers surmise that increased fasting glucose levels also increase the risk of dementia, and argue that a “vigilant and aggressive approach to the management of metabolic abnormalities” is needed to prevent a significant increase in dementia as the HIV-positive population ages.

Researchers working with the Hawaii Aging with HIV Cohort wanted to examine whether diabetes, fasting glucose and insulin resistance contribute to the relative risk of HIV-associated dementia (HAD) after a study published last year found that diabetes trebles the risk of dementia in HIV-negative people. The Hawaii Cohort, which began enrolment in October 2001, compares the neurological functioning of HIV-positive people over 50 with their younger (20-40) counterparts.

After excluding individuals with baseline cardiovascular problems, data from 96 younger and 103 older participants were analysed. Fifteen participants reported having been previously diagnosed with diabetes at baseline and a further two were classified during the study as having diabetes due to their having fasting glucose levels over 125mg/dL. Of the 17 individuals, 16 were in the older group, with only one in the younger group; the average age of those with diabetes was 53.3 years. The only significant difference between those with and without diabetes was that diabetic participants were more likely to have hypertension after adjusting for age; there was no differences in age, gender, ethnicity, current HAART use, current PI use, duration of infection, viral load or CD4 count.

The researchers found that a diagnosis of diabetes significantly correlated to a diagnosis of HAD when compared with all other diagnostic categories combined (OR = 4.3; p

When the researchers examined the link between fasting glucose (as a marker of insulin resistance) and dementia risk they found a stepwise pattern emerged, whereby fasting glucose levels were higher with increasing cognitive compromise. Those with normal cognitive functioning had a mean fasting glucose level of 88.35 mg/dL; those with a clinical diagnosis of Minor Cognitive Motor Disorder (MCMD), a less severe form of HAD, had a mean fasting glucose level of 93 mg/dL; and those with HAD had a mean fasting glucose level of 95.19 mg/dL. However, a univariate analysis of the association between glucose levels and an outcome of HAD versus any other diagnosis was not significant.

The authors note that their exploration of the links between insulin resistance and HAD are limited by a small sample size, but suggest “if confirmed, they could have important implications for clinical care of HIV-infected individuals, particularly older patients.”

Several studies have already found that HIV-positive people are at an increased risk of diabetes. Last year, the Multicenter AIDS Cohort Study (MACS) study found that, after adjusting for age and body mass, the diabetes prevalence rate in HIV-positive men not taking HAART was 2.11 times higher, and the rate in HIV-positive men on HAART was 5.36 times higher, than the prevalence rate in HIV-negative men.

Estimates of the incidence of HIV-associated dementia vary, depending on the definition of dementia being used. Researchers from John Hopkins University estimated in 1999 that 15% of HIV-infected people may develop dementia and that 30% may show some signs of neurological impairment. It is also unclear whether HAART has reduced the number of new cases of HIV-associated dementia. Some studies have shown reduced incidence and prevalence of dementia since HAART became available but other studies have failed to confirm this.

The underlying cause of the link between diabetes and dementia is poorly understood. The atherogenic effect of metabolic syndrome caused by HIV itself and exacerbated by certain anti-HIV medications is one possible answer. The authors suggest that, in addition, there may also be glucoregulatory-specific mechanisms involved. In HIV-negative individuals, three causes have been discussed: advanced glycation end products in the brain; the increased levels of amyloid in the brain; and diabetes’ effects on microvascular disease.

The authors conclude that their results suggest that “diabetes is independently associated with HAD” and argue that “dysregulation of glucose may pose a risk for cognitive impairment among HIV-infected nondiabetic individuals regardless of age.” They add, “further work to identify underlying mechanisms and subsequent modifiable pathways is warranted.”