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Metabolism. 2015 Apr;64(4):513-520. doi: 10.1016/j.metabol.2014.12.007. Epub 2014 Dec 26.

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

Author information

1
Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
2
Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
3
Division of Pediatric Endocrinology, Children's Hospital, Philadelphia, PA, USA.
4
National Heart, Lung and Blood Institute, Bethesda, MD, USA.
5
Institute for Diabetes, Obesity & Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
#
Contributed equally

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.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00953667.

KEYWORDS:

Glucose effectiveness; Insulin sensitivity; LPS; Race differences

PMID:
25579865
PMCID:
PMC4346476
DOI:
10.1016/j.metabol.2014.12.007
[Indexed for MEDLINE]
Free PMC Article

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