title: Associations of Circulating Lymphocyte Subpopulations with Type 2 Diabetes: Cross-Sectional Results from the Multi-Ethnic Study of Atherosclerosis (MESA).
abstract: OBJECTIVE
  Distinct lymphocyte subpopulations have been implicated in the regulation of glucose homeostasis and obesity-associated inflammation in mouse models of insulin resistance. Information on the relationships of lymphocyte subpopulations with type 2 diabetes remain limited in human population-based cohort studies.
  
  
  METHODS
  Circulating levels of innate (γδ T, natural killer (NK)) and adaptive immune (CD4+ naive, CD4+ memory, Th1, and Th2) lymphocyte subpopulations were measured by flow cytometry in the peripheral blood of 929 free-living participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Cross-sectional relationships of lymphocyte subpopulations with type 2 diabetes (n = 154) and fasting glucose and insulin concentrations were evaluated by generalized linear models.
  
  
  RESULTS
  Each standard deviation (SD) higher CD4+ memory cells was associated with a 21% higher odds of type 2 diabetes (95% CI: 1-47%) and each SD higher naive cells was associated with a 22% lower odds (95% CI: 4-36%) (adjusted for age, gender, race/ethnicity, and BMI). Among participants not using diabetes medication, higher memory and lower naive CD4+ cells were associated with higher fasting glucose concentrations (p<0.05, adjusted for age, sex, and race/ethnicity). There were no associations of γδ T, NK, Th1, or Th2 cells with type 2 diabetes, glucose, or insulin.
  
  
  CONCLUSIONS
  A higher degree of chronic adaptive immune activation, reflected by higher memory and lower naive CD4+ cells, was positively associated with type 2 diabetes. These results are consistent with a role of chronic immune activation and exhaustion augmenting chronic inflammatory diseases, and support the importance of prospective studies evaluating adaptive immune activation and type 2 diabetes.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont, United States of America.
authors.forename: Nels C
authors.initials: NC
authors.lastname: Olson
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont, United States of America.
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Doyle
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, United States of America; Kidney Research Institute, University of Washington, Seattle, Washington, United States of America.
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont, United States of America.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Huber
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont, United States of America.
authors.forename: Nancy Swords
authors.initials: NS
authors.lastname: Jenny
authors.affiliation: Collaborative Health Studies Coordinating Center, Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kronmal
authors.affiliation: Departments of Medicine, Epidemiology, Health Services, and Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America; Group Health Research Institute, Group Health Cooperative, Seattle, Washington, United States of America.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont, United States of America; Department of Biochemistry, University of Vermont College of Medicine, Burlington, Vermont, United States of America.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology; D001786:Blood Glucose; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005006:Ethnicity; D005260:Female; D005947:Glucose / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007328:Insulin / Q000097:blood; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D005947:Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; C517652:hemoglobin A1c protein, human