title: Activation of innate immunity modulates insulin sensitivity, glucose effectiveness and pancreatic β-cell function in both African ancestry and European ancestry healthy humans.
abstract: OBJECTIVE
  Insulin resistance is a risk factor for type 2 diabetes, and is associated with inflammatory cardiometabolic disease. Given differences between African ancestry (AA) and European ancestry (EA) in the epidemiology of type 2 diabetes as well as in response to inflammatory stress, we investigated potential race differences in glucose homeostasis responses during experimental endotoxemia in humans.
  
  
  METHODS
  Healthy volunteers (age 18-45 years, BMI 18-30 kg/m(2), 47% female, African-ancestry (AA, n=42) and European-ancestry (EA, n=106)) were recruited as part of the Genetics of Evoked Responses to Niacin and Endotoxemia (GENE) Study. Subjects underwent an inpatient endotoxin challenge (1 ng/kg LPS) and two frequently-sampled intravenous glucose tolerance tests (FSIGTT). Insulin and glucose values obtained during FSIGTT pre- and 24-hours post-LPS were analyzed using the minimal model.
  
  
  RESULTS
  FSIGTT derived insulin sensitivity index (SI), disposition index (DI) and glucose effectiveness (SG) decreased significantly following LPS (p<0.0001) while the acute insulin response to glucose (AIR(g)) increased (p<0.0001). Although expected race differences were observed in glucose homeostasis parameters at baseline prior to LPS e.g., lower SI (2.5 vs. 4.1 μU/L/min, p<0.0001) but higher AIR(g) (median 848 vs. 290 μU/L/min, p<0.0001) in AA vs. EA, the changes in glucose homeostasis responses to LPS were directionally and proportionally consistent across race e.g., SI median -35% in EA and -29% in AA and AIR(g) median +17% in EA and +26% in AA.
  
  
  CONCLUSIONS
  Both EA and AA samples modulated glucose and insulin homeostasis similarly during endotoxemia.
  
  
  CONCLUSIONS
  Race differences in response to environmental inflammatory stress are unlikely to be a substantial contributor to the observed difference in diabetes incidence and complications between EA and AA.
authors.affiliation: Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.|Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Jane F
authors.initials: JF
authors.lastname: Ferguson
authors.affiliation: Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Rhia Y
authors.initials: RY
authors.lastname: Shah
authors.affiliation: Division of Pediatric Endocrinology, Children's Hospital, Philadelphia, PA, USA.
authors.forename: Rachana
authors.initials: R
authors.lastname: Shah
authors.affiliation: National Heart, Lung and Blood Institute, Bethesda, MD, USA.
authors.forename: Nehal N
authors.initials: NN
authors.lastname: Mehta
authors.affiliation: Institute for Diabetes, Obesity & Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rickels
authors.affiliation: Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
mesh_terms: D000293:Adolescent; D000328:Adult; D044383:Black People; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000502:physiology*; D007333:Insulin Resistance / Q000208:ethnology / Q000276:immunology*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D044465:White People; D055815:Young Adult
chemical_list: D008070:Lipopolysaccharides; D005947:Glucose
keywords: Glucose effectiveness; Insulin sensitivity; LPS; Race differences