@article{d893767d5dcd4e1fb1bbf780fc60af2d,
title = "Impaired insulin sensitivity is associated with worsening cognition in HIV-infected patients",
abstract = "ObjectiveTo determine the association of insulin sensitivity and metabolic status with declining cognition in HIV-infected individuals.MethodsWe 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.ResultsPatients 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.ConclusionsThese findings suggest that hyperinsulinemia and impaired insulin sensitivity are associated with cognitive decline in antiretroviral therapy-treated HIV-infected patients.",
author = "Khuder, {Saja S.} and Suming Chen and Scott Letendre and Thomas Marcotte and Igor Grant and Donald Franklin and Rubin, {Leah H.} and Margolick, {Joseph B.} and Jacobson, {Lisa P.} and Ned Sacktor and Gypsyamber D'souza and Valentina Stosor and Lake, {Jordan E.} and Giovanna Rapocciolo and Mcarthur, {Justin C.} and Dickens, {Alex M.} and Haughey, {Norman J.}",
note = "Funding Information: The CHARTER group is affiliated with Johns Hopkins University; the Icahn School of Medicine at Mount Sinai; University of California, San Diego; University of Texas, Galveston; University of Washington, Seattle; and Washington University, St. Louis; is headquartered at the University of California, San Diego; and includes the following: director: Igor Grant, MD; codirectors: Scott L. Letendre, MD, Ronald J. Ellis, MD, PhD, Thomas D. Marcotte, PhD; center manager: Donald Franklin, Jr; neuromedical component: Ronald J. Ellis, MD, PhD (principal investigator [PI]), J. Allen McCutchan, MD; laboratory and virology component: Scott Letendre, MD (co-PI), Davey M. Smith, MD (co-PI); neurobehavioral component: Robert K. Heaton, PhD (PI), J. Hampton Atkinson, MD, Matthew Dawson; imaging component: Christine Fennema-Notestine, PhD (PI), Michael J. Taylor, PhD, Rebecca Theilmann, PhD; data management component: Anthony C. Gamst, PhD (PI), Clint Cushman; statistics component: Ian Abramson, PhD (PI), Florin Vaida, PhD; Johns Hopkins University site: Ned Sacktor (PI), Vincent Rogalski; Icahn School of Medicine at Mount Sinai site: Susan Morgello, MD (Co-PI), and David Simpson, MD (Co-PI), Letty Mintz, NP; University of California, San Diego site: J. Allen McCutchan, MD (PI); University of Washington, Seattle site: Ann Collier, MD (Co-PI) and Christina Marra, MD (co-PI), Sher Storey, PA-C; University of Texas, Galveston site: Benjamin Gelman, MD, PhD (PI), Eleanor Head, RN, BSN; and Washington University, St. Louis site: David Clifford, MD (PI), Muhammad Al-Lozi, MD, Mengesha Teshome, MD. MACS with centers at Baltimore (U01-AI35042): Johns Hopkins University Bloomberg School of Public Health: Joseph B. Margolick (PI), Jay Bream, Todd Brown, Adrian Dobs, Michelle Estrella, W. David Hardy, Lisette Johnson-Hill, Sean Leng, Anne Monroe, Cynthia Munro, Michael W. Plankey, Wendy Post, Ned Sacktor, Jennifer Schrack, Chloe Thio; Chicago (U01-AI35039): Feinberg School of Medicine, Northwestern University, and Cook County Bureau of Health Services: Steven M. Wolinsky (PI), Sheila Badri, Dana Gabuzda, Frank J. Palella, Jr, Sudhir Penugonda, John P. Phair, Susheel Reddy, Matthew Stephens, Linda Teplin; Los Angeles (U01-AI35040): University of California, UCLA Schools of Public Health and Medicine: Roger Detels (PI), Otoniel Mart{\'i}nez-Maza (PI), Peter Anton, Robert Bolan, Elizabeth Breen, Anthony Butch, Shehnaz Hussain, Beth Jamieson, John Oishi, Harry Vinters, Dorothy Wiley, Mallory Witt, Otto Yang, Stephen Young, Zuo Feng Zhang; Pittsburgh (U01-AI35041): University of Pittsburgh, Graduate School of Public Health: Charles R. Rinaldo (PI), James T. Becker, Phalguni Gupta, Kenneth Ho, Lawrence A. Kingsley, Susan Koletar, Jeremy J. Martinson, John W. Mellors, Anthony J. Silvestre, Ronald D. Stall; Data Coordinating Center (UM1-AI35043): Johns Hopkins University Bloomberg School of Public Health: Lisa P. Jacobson (PI), Gypsyamber D{\textquoteright}Souza (PI), Alison Abraham, Keri Althoff, Michael Collaco, Priya Duggal, Sabina Haberlen, Eithne Keelaghan, Heather McKay, Alvaro Mu{\~n}oz, Derek Ng, Anne Rostich, Eric C. Seaberg, Sol Su, Pamela Surkan, Nicholas Wada. Institute of Allergy and Infectious Diseases: Robin E. Huebner; National Cancer Institute: Geraldina Dominguez. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases, with additional cofunding from the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute of Mental Health. Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute and the National Institute on Deafness and Communication Disorders. MACS data collection is also supported by UL1-TR001079 (Johns Hopkins Institute for Clinical and Translational Research) from the National Center for Advancing Translational Sciences, a component of the NIH, and NIH Roadmap for Medical Research. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the NIH, Johns Hopkins Institute for Clinical and Translational Research, or National Center for Advancing Translational Sciences. The MACS website is located at aidscohortstudy.org/. Funding Information: This work was supported by NIH awards AA0017408, MH077542, MH075673, AG034849 (N.J.H. and J.C.M.), MH071150 (N.S.), and K23AI110532 (J.E.L.). CHARTER was supported by awards N01 MH22005, HHSN271201000036C, and HHSN271201000030C (I.G., T.M., S.L.). Publisher Copyright: {\textcopyright} American Academy of Neurology.",
year = "2019",
month = mar,
day = "19",
doi = "10.1212/WNL.0000000000007125",
language = "English (US)",
volume = "92",
pages = "E1344--E1353",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "12",
}