PT  - JOURNAL ARTICLE
AU  - Khuder, Saja S.
AU  - Chen, Suming
AU  - Letendre, Scott
AU  - Marcotte, Thomas
AU  - Grant, Igor
AU  - Franklin, Donald
AU  - Rubin, Leah H.
AU  - Margolick, Joseph B.
AU  - Jacobson, Lisa P.
AU  - Sacktor, Ned
AU  - D'Souza, Gypsyamber
AU  - Stosor, Valentina
AU  - Lake, Jordan E.
AU  - Rapocciolo, Giovanna
AU  - McArthur, Justin C.
AU  - Dickens, Alex M.
AU  - Haughey, Norman J.
TI  - Impaired insulin sensitivity is associated with worsening cognition in HIV-infected patients
AID  - 10.1212/WNL.0000000000007125
DP  - 2019 Mar 19
TA  - Neurology
PG  - e1344--e1353
VI  - 92
IP  - 12
4099  - http://n.neurology.org/content/92/12/e1344.short
4100  - http://n.neurology.org/content/92/12/e1344.full
SO  - Neurology2019 Mar 19; 92
AB  - 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.ART=antiretroviral therapy; BMI=body mass index; CHARTER=Central Nervous System HIV Anti-Retroviral Therapy Effects Research; CI=confidence interval; GLUT=glucose transporter; HAND=HIV-Associated Neurocognitive Disorders; HCV=hepatitis C virus; HDL=high-density lipoprotein; HOMA-IR=homeostatic model assessment of insulin resistance; LDL=low-density lipoprotein; MACS=Multicenter AIDS Cohort Study; PI=protease inhibitor; TC=total cholesterol