Activation of Innate Immunity Modulates Insulin Sensitivity, Glucose Effectiveness and Pancreatic β-Cell Function in Both African Ancestry and European Ancestry Healthy Humans

• Published in: Metabolism, clinical and experimental Vol. 64; no. 4; pp. 513 - 520
• Main Authors: Ferguson, Jane F, Shah, Rhia Y, Shah, Rachana, Mehta, Nehal N, Rickels, Michael R, Reilly, Muredach P
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2015
• Subjects: Adolescent; Adult; African Continental Ancestry Group; Endocrinology & Metabolism; European Continental Ancestry Group; Female; Glucose - metabolism; Glucose effectiveness; Glucose Tolerance Test; Humans; Immunity, Innate - drug effects; Immunity, Innate - physiology; Insulin Resistance - ethnology; Insulin Resistance - immunology; Insulin sensitivity; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - physiology; Lipopolysaccharides - pharmacology; LPS; Male; Middle Aged; Race differences; Young Adult; CRP; C-reactive protein; DI; AIR g; FSIGTT; frequently-sampled intravenous glucose tolerance test; LPS; insulin sensitivity; disposition index; EA; AA; African ancestry; IL-1RA; interleukin 1 receptor agonist; acute insulin response to glucose; Homeostasis Model Assessment; GENE; HOMA; S G; lipopolysaccharide; Genetics of Evoked Responses to Niacin and Endotoxemia; European ancestry; glucose effectiveness; S I; Race differences; AIRg; Insulin sensitivity; SG; SI; Glucose effectiveness
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2014.12.007

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/m2 , 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 (AIRg ) 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 AIRg (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 AIRg median + 17% in EA and + 26% in AA. Conclusion Both EA and AA samples modulated glucose and insulin homeostasis similarly during endotoxemia. Implications 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.