Authors: McCutchan JA, Marquie-Beck J, FitzSimons C, Letendre S, Ellis RJ, Heaton R, Wolfson T, Marra C, Ances B, Grant I, for the CHARTER Group |
Abstract:Objective: Both central obesity and diabetes are associated with cognitive
impairment in HIV-uninfected persons. We evaluated the relationships of HIVAssociated
Neurocognitive Disorder (HAND) to central obesity (waist
circumference = WC), body mass index (BMI), diabetes (DM), and multiple other
metabolic variables in a cross-sectional substudy of HIV+ patients who were
examined in CHARTER, a prospective study of 1574 patients at 6 US academic
HIV clinics.
Methods: HIV+ volunteers (n = 130) provided fasting blood samples and
underwent extensive neuropsychological evaluation that adjusts for age,
education, gender and race/ethnicity. Neurocognitive impairment (NCI) was
defined by both clinical ratings of global cognitive functioning (global impairment
rating ≥ 5) and global deficit scores (GDS > 0.5). Demographics, biomarkers of
HIV disease, metabolic variables including leptin levels and HOMA (a measure of
Insulin resistance), anthropomorphic measures (WC and BMI), CART history,
other drug exposures, and self reported diabetes (DM) were examined in
univariate analyses and multivariate models predicting NCI. Based on the
availability of data for these models, we examined BMI alone (n=90) and BMI
plus WC (n=55) as correlates of NCI.
Results: NCI was diagnosed in 40% of 130 participants. In univariate analyses,
age, longer duration of HIV infection, and WC were associated with NCI, but
other variable including BMI, leptin levels, and HOMA were not. Self-reported
diabetes was associated with NCI in the substudy and in those of age > 55, but
not those < 55, in the entire CHARTER cohort. Multivariate logistic regression
analyses demonstrated that diagnosis of AIDS (OR = 50, p = .02); diagnosis of
DM (OR = 18, p = .07); and WC (OR = 1.34 per cm, p = .001) increased the risk
of NCI, but that greater body mass (OR = .69. p = .04) was protective.
Conclusions: As in HIV-uninfected persons, diabetes and central obesity were
associated with a higher prevalence of NCI in HIV+ persons, but increased body
mass (BMI) was protective when the deleterious effects of central obesity are
accounted for in the model. Diabetes appeared to be associated with NCI only in
older patients. The mechanisms by which diabetes and central obesity, both of
which are associated with insulin resistance, contribute to NCI are unclear.
Avoidance of antiretroviral drugs that induce central obesity might help to protect
from or reverse neurocognitive impairment in HIV-infected persons. |