The contribution of race and diabetes status to metabolic flexibility in humans
Open accessAbstract
Factors controlling metabolic flexibility (MF), the ability of the body to switch from fat to carbohydrate oxidation in response to feeding or with insulin administration, are being actively investigated. We sought to determine the effects of race (African American vs Caucasian) and diabetes status (nondiabetic vs type 2 diabetes mellitus individuals) on MF to glucose in humans. Respiratory quotient (RQ) and macronutrient substrate utilization were evaluated by indirect calorimetry during baseline (fasting) and hyperinsulinemic-euglycemic clamp (insulin infusion of 120 mU x m(-2) x min(-1)); DeltaRQ (MF) = clamp RQ - fasting RQ. The study included 168 human subjects of different races (55 African Americans, 113 Caucasians), sex (73 men, 95 women), ages (18-73 years), body mass index (19.3-47.7 kg/m(2)), and diabetes status (89 nondiabetic, 79 type 2 diabetes mellitus subjects). Metabolic flexibility was negatively correlated (P < .01) with age (r = - 0.41), fasting RQ (r = -0.22), fasting glucose (r = -0.55), insulin (r = -0.40), and triglyceride (r = -0.44) concentrations; whereas a positive association was observed with insulin sensitivity (r = 0.69, P < .0001). Insulin sensitivity, fasting RQ, triglyceride concentrations, diabetes status, and race accounted for 71% of the variability in MF with insulin sensitivity being the main determinant factor (model R(2) = 0.48, P < .0001). After controlling for the significant predictors, MF was higher in African Americans vs Caucasians (mean +/- SEM 0.080 +/- 0.004 vs 0.069 +/- 0.002, P = .008) and in nondiabetic vs type 2 diabetes mellitus subjects (P = .003). This study confirms that insulin sensitivity is the major contributor to MF in humans, but provides the novel findings that African Americans have significantly greater MF than Caucasians even after adjusting for insulin sensitivity and diabetes status.
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Tissue glucose availability explained about half of the increase in glucose oxidation during euglycemic-hyperinsulinemic clamps.
“Indeed, tissue glucose availability explained ~50% of the increase in glucose oxidation during euglycemic-hyperinsulinemic clamps (10,27).”
From Metabolic flexibility to lipid availability during exercise is enhanced in individuals with high insulin sensitivity (2018) · cites this paper as [27]
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- Authors
- Stull, A. J., Galgani, J. E., Johnson, W. D., & Cefalu, W. T.
- Affiliations
- Pennington Biomedical Research Center (US)
- Corresponding author
- Cefalu, William T.
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 59
- Issue
- 9
- Pages
- 1358-1364
- ISSN
- 0026-0495 (ISSN-L)
- PMC
- PMC4240223
- OpenAlex
- W2126539414
- Cited by
- 47
- References
- 21
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 3 · 2013: 4 · 2012: 4
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R55DK060126, R01DK060126, P30DK072476)
- National Center for Complementary and Integrative Health (P50AT002776, R21AT002995, T32AT004094)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- metabolic flexibility, race, African Americans, type 2 diabetes, insulin sensitivity, respiratory quotient, substrate utilization, hyperinsulinemic-euglycemic clamp, fasting blood glucose, triglycerides, age
- MeSH terms
- Adolescent, Adult, Aged, Black or African American, Blood Glucose, Body Composition, Diabetes Mellitus, Type 2, Energy Metabolism, Fasting, Female, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Triglycerides, Glucose Clamp Technique, Body Mass Index, White People
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