Genome-wide linkage scans for prediabetes phenotypes in response to 20 weeks of endurance exercise training in non-diabetic whites and blacks: the HERITAGE Family Study
Abstract
Aims/hypothesis Impaired insulin secretion, insulin action, insulin-independent glucose effectiveness, glucose tolerance and the associated abnormalities in insulin and glucose metabolism phenotypes are precursors of type 2 diabetes. Genome-wide multipoint variance component linkage scans were carried out using 654 markers to identify quantitative trait loci for insulin sensitivity, acute insulin response to glucose, disposition index and glucose effectiveness training responses in whites and blacks in the HERITAGE Family Study. Methods These phenotypes were obtained from an IVGTT with the minimal model. The distributions of insulin sensitivity, acute insulin response to glucose and disposition index training responses (post-training minus baseline) were approximately normalised using a square-root transformation. All phenotypes were adjusted for the effects of age, BMI and their respective baseline values within sex and generation by race prior to linkage scans. Results In blacks, a promising linkage with a maximum lod score of 3.1 on 19q (54-62 Mb) for glucose effectiveness training response was found. Six interesting linkages with lod scores of at least 1.0 were found for disposition index training response in whites. They included 1p (30 Mb), 3q (152 Mb), 6p (23-42 Mb), 7q (95-96 Mb), 10p (15 Mb) and 12q (119-126 Mb). Conclusions/interpretation Quantitative trait loci for 20 weeks of endurance exercise training responses in insulin action and glucose metabolism phenotypes…
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The heritability of exercise-induced changes reached about 30% for plasma HDL-C and triglycerides and about 20% to 25% for indicators of insulin metabolism and resting systolic blood pressure.
“In fact, the heritability of the changes induced by the exercise program reached about 30% for plasma HDL-C and TG [26] and about 20% to 25% for indicators of insulin metabolism and resting SBP [29], [30].”
From Adverse metabolic response to regular exercise: is it a rare or common occurrence? (2012) · cites this paper as [29]
Cites
Effects of Exercise Training on Glucose Homeostasis
Boulé, N. G., Weisnagel, S. J., Lakka, T. A., Tremblay, A., Bergman, R. N., Rankinen, T., Leon, A. S., Skinner, J. S., Wilmore, J. H., Rao, D. C., et al. (2005) · Diabetes Care · doi:10.2337/diacare.28.1.108 · Cited by 356 · see citing works
Self-citationVaag, A., Henriksen, J. E., & Beck-Nielsen, H. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115656 · Cited by 299 · cited 1× · see citing works
“The storage of glucose as glycogen in human skeletal muscles is frequently impaired in patients with type 2 diabetes and their non-diabetic relatives, partially because of impaired activation of the GYS1 gene by insulin [29].”
BackgroundAims, design, and measurement protocol
BOUCHARD, C., LEON, A. S., RAO, D. C., SKINNER, J. S., WlLMORE, J. H., & GAGNON, J. (1995) · Medicine & Science in Sports & Exercise · doi:10.1249/00005768-199505000-00015 · Cited by 271 · see citing works
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Slow-wave sleep and the risk of type 2 diabetes in humans
Tasali, E., Leproult, R., Ehrmann, D. A., & Van Cauter, E. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706446105 · Cited by 921 · see citing works
Adverse metabolic response to regular exercise: is it a rare or common occurrence?
Bouchard, C., Blair, S. N., Church, T. S., Earnest, C. P., Hagberg, J. M., Häkkinen, K., Jenkins, N. T., Karavirta, L., Kraus, W. E., Leon, A. S., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037887 · Cited by 389 · see citing works
“Numbers of adverse responders reached 12.2% for SBP, 10.4% for TG, and 13.3% for HDL-C.”
BackgroundInfluentialSelf-citationA transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype
Keller, P., Vollaard, N. B. J., Gustafsson, T., Gallagher, I. J., Sundberg, C. J., Rankinen, T., Britton, S. L., Bouchard, C., Koch, L. G., & Timmons, J. A. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00634.2010 · Cited by 261 · see citing works
Self-citationExercise training response heterogeneity: physiological and molecular insights.
Sparks, L. M. (2017) · Diabetologia · doi:10.1007/s00125-017-4461-6 · Cited by 160 · see citing works
SARZYNSKI, M. A., RICE, T. K., DESPRÉS, J.-P., PÉRUSSE, L., TREMBLAY, A., STANFORTH, P. R., TCHERNOF, A., BARBER, J. L., FALCIANI, F., CLISH, C., et al. (2022) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002859 · Cited by 62 · see citing works
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- Authors
- An, P., Teran-Garcia, M., Rice, T., Rankinen, T., Weisnagel, S. J., Bergman, R. N., Boston, R. C., Mandel, S., Stefanovski, D., Leon, A. S., Skinner, J. S., Rao, D. C., & Bouchard, C.
- Affiliations
- Washington University in St. Louis (US)
- Pennington Biomedical Research Center (US)
- Université Laval (CA)
- University of Southern California (US)
- University of Pennsylvania (US)
- University of Minnesota (US)
- Indiana University Bloomington (US)
- Corresponding author
- An, P.
- ORCID
- Venue
- Diabetologia
- Published
- 2005-05-03
- Volume
- 48
- Issue
- 6
- Pages
- 1142-1149
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2008270315
- Cited by
- 54
- References
- 3
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 2
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL047327, HL 47321, HL 45670, HL47323, R01HL047317, HL 47327, R01HL047323, HL47317, R01HL045670, R01HL047321)
- National Center for Research Resources (M01RR000400)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- prediabetes, endurance training, insulin sensitivity, acute insulin response to glucose, disposition index, glucose effectiveness, quantitative trait loci, genome-wide linkage analysis, type 2 diabetes risk, racial differences, chromosome 19q, chromosome 6p, chromosome 7q, HERITAGE Family Study
- MeSH terms
- Adolescent, Adult, Chromosome Mapping, Family, Female, Genetic Markers, Humans, Lod Score, Male, Middle Aged, North America, Phenotype, Physical Endurance, Physical Fitness, Prediabetic State, Reference Values, Genome, Human, Body Mass Index, Quantitative Trait Loci, Black People, White People
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