Jane F Ferguson1,2, Rhia Y Shah1, Rachana Shah3, Nehal N Mehta4, Michael R Rickels5, Muredach P Reilly1. 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.
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.
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.
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