Jane Ferguson
Last active: 3/3/2020

Activation of innate immunity modulates insulin sensitivity, glucose effectiveness and pancreatic β-cell function in both African ancestry and European ancestry healthy humans.

Ferguson JF, Shah RY, Shah R, Mehta NN, Rickels MR, Reilly MP
Metabolism. 2015 64 (4): 513-520

PMID: 25579865 · PMCID: PMC4346476 · DOI:10.1016/j.metabol.2014.12.007

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.

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.

Copyright © 2015 Elsevier Inc. All rights reserved.

MeSH Terms (15)

Adolescent Adult African Continental Ancestry Group European Continental Ancestry Group Female Glucose Glucose Tolerance Test Humans Immunity, Innate Insulin-Secreting Cells Insulin Resistance Lipopolysaccharides Male Middle Aged Young Adult

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