A1 Refereed original research article in a scientific journal
Impaired insulin sensitivity is associated with worsening cognition in HIV-infected patients
Authors: Khuder SS, Chen SM, Letendre S, Marcotte T, Grant I, Franklin D, Rubin LH, Margolick JB, Jacobson LP, Sacktor N, D'Souza G, Stosor V, Lake JE, Rapocciolo G, McArthur JC, Dickens AM, Haughey NJ, Haughey NJ
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Publication year: 2019
Journal: Neurology
Journal name in source: NEUROLOGY
Journal acronym: NEUROLOGY
Volume: 92
Issue: 12
First page : E1344
Last page: E1353
Number of pages: 10
ISSN: 0028-3878
eISSN: 1526-632X
DOI: https://doi.org/10.1212/WNL.0000000000007125
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.