Impaired insulin sensitivity is associated with worsening cognition in HIV-infected patients.

TitleImpaired insulin sensitivity is associated with worsening cognition in HIV-infected patients.
Publication TypeJournal Article
Year of Publication2019
AuthorsKhuder, SS, Chen, S, Letendre, S, Marcotte, TD, 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
JournalNeurology
Volume92
Issue12
Paginatione1344-e1353
Date Published2019 03 19
ISSN1526-632X
KeywordsAdult, Anti-HIV Agents, C-Peptide, Case-Control Studies, CHARTER, Cognition, Cognitive Dysfunction, Cohort Studies, Female, HIV Infections, Humans, Hyperinsulinism, Insulin Resistance, Internal, Lipoproteins, Male, Middle Aged
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.

DOI10.1212/WNL.0000000000007125
Alternate JournalNeurology
PubMed ID30787163
PubMed Central IDPMC6511093
Grant ListU01 AI035042 / AI / NIAID NIH HHS / United States
P30 MH075673 / MH / NIMH NIH HHS / United States
U01 HL146201 / HL / NHLBI NIH HHS / United States
R01 MH110246 / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
P01 MH105280 / MH / NIMH NIH HHS / United States