Saja S Khuder1, Suming Chen1, Scott Letendre1, Thomas Marcotte1, Igor Grant1, Donald Franklin1, Leah H Rubin1, Joseph B Margolick1, Lisa P Jacobson1, Ned Sacktor1, Gypsyamber D'Souza1, Valentina Stosor1, Jordan E Lake1, Giovanna Rapocciolo1, Justin C McArthur1, Alex M Dickens2, Norman J Haughey2. 1. From the Departments of Neurology (S.S.K., S.C., L.H.R., N.S., J.C.M., N.J.H.) and Psychiatry (N.J.H.), Johns Hopkins University School of Medicine, Baltimore, MD; HIV Neurobehavioral Research Program and Department of Psychiatry (S.L., T.M., I.G., D.F.), School of Medicine, University of California, San Diego, La Jolla; Department of Epidemiology (J.B.M., L.P.J., G.D.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Medicine (V.S.), Division of Infectious Diseases, and Department of Surgery (V.S.), Division of Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL; University of Texas Health Sciences Center (J.E.L.), Houston; Infectious Disease and Microbiology (G.R.), University of Pittsburg, PA; and Turku Centre for Biotechnology (A.M.D.), Turku University, Finland. 2. From the Departments of Neurology (S.S.K., S.C., L.H.R., N.S., J.C.M., N.J.H.) and Psychiatry (N.J.H.), Johns Hopkins University School of Medicine, Baltimore, MD; HIV Neurobehavioral Research Program and Department of Psychiatry (S.L., T.M., I.G., D.F.), School of Medicine, University of California, San Diego, La Jolla; Department of Epidemiology (J.B.M., L.P.J., G.D.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Medicine (V.S.), Division of Infectious Diseases, and Department of Surgery (V.S.), Division of Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL; University of Texas Health Sciences Center (J.E.L.), Houston; Infectious Disease and Microbiology (G.R.), University of Pittsburg, PA; and Turku Centre for Biotechnology (A.M.D.), Turku University, Finland. nhaughe1@jhmi.edu alex.dickens@utu.fi.
Abstract
OBJECTIVE: To determine the association of insulin sensitivity and metabolic status with declining cognition in HIV-infected individuals. METHODS: We conducted targeted clinical and metabolic measures in longitudinal plasma samples obtained from HIV-infected patients enrolled in the Central Nervous System HIV Anti-Retroviral Therapy Effects Research Study (CHARTER). Findings were validated with plasma samples from the Multicenter AIDS Cohort Study (MACS). Patients were grouped according to longitudinally and serially assessed cognitive performance as having stably normal or declining cognition. RESULTS: Patients with declining cognition exhibited baseline hyperinsulinemia and elevated plasma c-peptide levels with normal c-peptide/insulin ratios, suggesting that insulin production was increased, but insulin clearance was normal. The association of hyperinsulinemia with worsening cognition was further supported by low high-density lipoprotein (HDL), high low-density lipoprotein/HDL ratio, and elevated cholesterol/HDL ratio compared to patients with stably normal cognition. CONCLUSIONS: These findings suggest that hyperinsulinemia and impaired insulin sensitivity are associated with cognitive decline in antiretroviral therapy-treated HIV-infected patients.
OBJECTIVE: To determine the association of insulin sensitivity and metabolic status with declining cognition in HIV-infected individuals. METHODS: We conducted targeted clinical and metabolic measures in longitudinal plasma samples obtained from HIV-infected patients enrolled in the Central Nervous System HIV Anti-Retroviral Therapy Effects Research Study (CHARTER). Findings were validated with plasma samples from the Multicenter AIDS Cohort Study (MACS). Patients were grouped according to longitudinally and serially assessed cognitive performance as having stably normal or declining cognition. RESULTS: Patients with declining cognition exhibited baseline hyperinsulinemia and elevated plasma c-peptide levels with normal c-peptide/insulin ratios, suggesting that insulin production was increased, but insulin clearance was normal. The association of hyperinsulinemia with worsening cognition was further supported by low high-density lipoprotein (HDL), high low-density lipoprotein/HDL ratio, and elevated cholesterol/HDL ratio compared to patients with stably normal cognition. CONCLUSIONS: These findings suggest that hyperinsulinemia and impaired insulin sensitivity are associated with cognitive decline in antiretroviral therapy-treated HIV-infected patients.
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