Glucose tolerance and free fatty acid metabolism in adults with variations in TCF7L2 rs7903146 |
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| Affiliation: | 1. Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai, PR China;2. Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN;1. Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA;2. Department of Kinesiology, University of Texas in El Paso, 500 University Ave, El Paso, TX 79968, USA;3. Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL 32804, USA;4. Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL 32827, USA;5. Department of Radiology, University of Washington Medical Center, 1959 NE Pacific St, Seattle, WA 98195, USA;6. Department of Clinical and Diagnostic Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA;1. Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada;2. Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece;3. Medical Library, McGill University Health Centre, Montreal, Quebec, Canada;1. Department of Agricultural, Food and Nutritional Science, University of Alberta, 4-002 Li Ka Shing Centre, Edmonton, AB, Canada T6G 2E1;2. Department of Pediatrics, University of Alberta, 11405-87 Avenue, Edmonton, AB, Canada T6G 2R3;3. Department of Exercise Science, Concordia University, 7141 Sherbrooke Street West, Office SP-165.06, Montreal, QB, Canada H4B1R6;4. Department of Medicine, 1-116 Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, AB, Canada T6G 2E1;5. Department of Kinesiology, California State University, Fullerton, 800 N. State College Blvd, CA 92834, USA;1. Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8;2. Department of Pharmacology and Therapeutics, Children''s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada R3E 3P4;3. Department of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8;4. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8;5. Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada M5S 1A8;1. Department of Clinical and Experimental Medicine, University of Pisa, Italy;2. Service Endocrinologie-Diabétologie, Centre Hospitalo-Universitaire (CHU), University Rennes 1, Rennes, France;3. Institute of Cardiovascular and Medical Sciences BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK;4. CNR Institute of Neuroscience, Padova, Italy |
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| Abstract: | ObjectiveTCF7L2 variant rs7903146 is associated with increased risk for type 2 diabetes. We investigated the effect of TCF7L2 variant rs7903146 and glucose tolerance on free fatty acid (FFA) metabolism.Research Design and MethodsWe recruited 120 individuals, half homozygous for the major CC allele and half homozygous for the minor TT allele at rs7903146; each underwent a 2-h, 75 g oral glucose tolerance test (OGTT). Plasma glucose, insulin and free fatty acid concentrations were measured on blood collected before and during the OGTT.ResultsTotal FFA concentrations and percent FA species during OGTT were not different in CC and TT carriers when males and females were considered together. However, monounsaturated fatty acid (MUFA) concentrations and percentages were greater in TT than CC females during the OGTT. TT carriers with high HOMA-IR had significantly greater fasting FFA concentrations, lower disposition index (DI) and greater AUC of glucose than high HOMA-IR CC carriers, whereas no such differences were observed in the low HOMA-IR group. We found that fasting (826 ± 25 vs. 634 ± 22 μmol/L, P < 0.0001) and OGTT plasma FFA concentrations were greater in IGT than NGT subjects, and the difference remained after adjusting for sex, age, BMI, and genotype. Finally, IGT subjects had greater MUFA concentrations and percentages than NGT subjects during OGTT.ConclusionsDespite similar fasting insulin and glucose, fasting plasma FFA are greater in IGT than NGT adults. Insulin resistance and sex influence plasma FFA responses amongst carriers of the minor T allele of TCF7L2 rs7903146. |
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