title: Monocytes expand with immune dysregulation and is associated with insulin resistance in older individuals with chronic HIV.
abstract: BACKGROUND
  Rates of insulin resistance are increased in HIV-infected patients on stable antiretroviral therapy (ART). Such increase may partially be due to HIV-induced immune dysregulation involving monocytes (MO) and its subsets.
  
  
  METHODS
  Cross-sectional analysis of 141 HIV-infected subjects age ≥ 40 years on stable ART. Homeostatic model assessment-insulin resistance (HOMA-IR) and rates of metabolic syndrome were calculated. Subjects were classified by fasting glucose and oral glucose tolerance test (OGTT) into clinical diabetes categories. Multi-parametric flow cytometry was used to determine MO subset percentages: [classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)), non-classical (CD14(low/+)CD16(++)), and a recently identified fourth (CD14(low/+)CD16(-)) 'transitional' MO subset] and percentage of activated (CD38(+)HLA-DR(+)) CD8 T cells. Absolute levels of cells were calculated using clinical CBC and T cell subset data. Multiple plasma soluble biomarkers were assessed by Luminex technology.
  
  
  RESULTS
  Median age 50 years, CD4 count (percent) 505 cells/µL (29%), and 89% male. Total MO (r=-0.23, p=0.006) and classical and non-classical MO subsets correlated negatively with CD4 percent. No correlations were seen with CD4 count as absolute values. Log-total MO and log-classical MO predicted HOMA-IR independently of HIV immuno-virologic and diabetes risk factors (β=0.42, p=0.02 and β=0.35, p=0.02, respectively) and were increased in subjects with metabolic syndrome (p=0.03 and p=0.05 respectively). Total and/or subset MO levels correlated with multiple soluble plasma biomarkers including CRP, IL-6, MMP-9, MPO, SAA, SAP and tPAI-1, with tPAI-1 independently predicting HOMA-IR (β=0.74, p<0.001).
  
  
  CONCLUSIONS
  MO levels increase with worsening HIV immune dysregulation as assessed by CD4 percent. CD4 percent may provide additional information about MO and metabolic risk in this population beyond absolute values. MO, and specifically classical MO, may contribute to insulin resistance and metabolic syndrome during chronic HIV infection. Multiple soluble plasma biomarkers including tPAI-1 increase with increase in MO. Levels of tPAI-1 independently predict the development of insulin resistance.
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Shikuma
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Dominic C
authors.initials: DC
authors.lastname: Chow
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Louie Mar A
authors.initials: LM
authors.lastname: Gangcuangco
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Guangxiang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Blood Systems Research Institute, San Francisco, California, United States of America.
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Keating
authors.affiliation: Blood Systems Research Institute, San Francisco, California, United States of America ; University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America ; Queen's Medical Center, Honolulu, Hawaii, United States of America.
authors.forename: Todd B
authors.initials: TB
authors.lastname: Seto
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America ; Queen's Medical Center, Honolulu, Hawaii, United States of America.
authors.forename: Nisha
authors.initials: N
authors.lastname: Parikh
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Kalpana J
authors.initials: KJ
authors.lastname: Kallianpur
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America ; Straub Clinic and Hospital, Honolulu, Hawaii, United States of America.
authors.forename: Beau K
authors.initials: BK
authors.lastname: Nakamoto
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Lorna S
authors.initials: LS
authors.lastname: Nagamine
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Lishomwa C
authors.initials: LC
authors.lastname: Ndhlovu
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Barbour
mesh_terms: D000367:Age Factors; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001786:Blood Glucose; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D007333:Insulin Resistance / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D024821:Metabolic Syndrome / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001786:Blood Glucose