Amra Jujić1,2,3, Peter M Nilsson4, Naeimeh Atabaki-Pasdar4, Anna Dieden5, Tiinamaija Tuomi4,6,7,8, Paul W Franks4,9, Jens Juul Holst10,11, Signe Sørensen Torekov10,11, Susana Ravassa12,13,14, Javier Díez12,13,14,15, Margaretha Persson4, Emma Ahlqvist4,3, Olle Melander4, Maria F Gomez4,3, Leif Groop4,3,6, Martin Magnusson4,2,16,17. 1. Department of Clinical Sciences, Lund University, Malmö, Sweden amra.jujic@med.lu.se. 2. Department of Cardiology, Skåne University Hospital, Malmö, Sweden. 3. Lund University Diabetes Centre, Lund University, Malmö, Sweden. 4. Department of Clinical Sciences, Lund University, Malmö, Sweden. 5. Department of Biomedical Science, Malmö University, Malmö, Sweden. 6. Folkhälsan Research Centre, Biomedicum, and Research Program Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland. 7. Department of Endocrinology, Helsinki University Hospital, Helsinki, Finland. 8. Finnish Institute of Molecular Medicine, University of Helsinki, Helsinki, Finland. 9. Department of Nutrition, Harvard School of Public Health, Boston, MA. 10. Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark. 11. Novo Nordisk Foundation Center for Basic Metabolic Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark. 12. Program of Cardiovascular Diseases, Center for Applied Medical Research, University of Navarra, Pamplona, Spain. 13. CIBERCV, Carlos III Institute of Health, Madrid, Spain. 14. Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain. 15. Department of Cardiology and Cardiac Surgery and Department of Nephrology, University of Navarra Clinic, Pamplona, Spain. 16. Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden. 17. Hypertension in Africa Research Team, North-West University Potchefstroom, Potchefstroom, South Africa.
Abstract
OBJECTIVE: While existing evidence supports beneficial cardiovascular effects of glucagon-like peptide 1 (GLP-1), emerging studies suggest that glucose-dependent insulinotropic peptide (GIP) and/or signaling via the GIP receptor may have untoward cardiovascular effects. Indeed, recent studies show that fasting physiological GIP levels are associated with total mortality and cardiovascular mortality, and it was suggested that GIP plays a role in pathogenesis of coronary artery disease. We investigated the associations between fasting and postchallenge GIP and GLP-1 concentrations and subclinical atherosclerosis as measured by mean intima-media thickness in the common carotid artery (IMTmeanCCA) and maximal intima-media thickness in the carotid bifurcation (IMTmaxBulb). RESEARCH DESIGN AND METHODS: Participants at reexamination within the Malmö Diet and Cancer-Cardiovascular Cohort study (n = 3,734, mean age 72.5 years, 59.3% women, 10.8% subjects with diabetes, fasting GIP available for 3,342 subjects, fasting GLP-1 available for 3,299 subjects) underwent oral glucose tolerance testing and carotid ultrasound. RESULTS: In linear regression analyses, each 1-SD increment of fasting GIP was associated with increased (per mm) IMTmeanCCA (β = 0.010, P = 0.010) and IMTmaxBulb (β = 0.014; P = 0.040) in models adjusted for known risk factors and glucose metabolism. In contrast, each 1-SD increment of fasting GLP-1 was associated with decreased IMTmaxBulb (per mm, β = -0.016, P = 0.014). These associations remained significant when subjects with diabetes were excluded from analyses. CONCLUSIONS: In a Swedish elderly population, physiologically elevated levels of fasting GIP are associated with increased IMTmeanCCA, while GLP-1 is associated with decreased IMTmaxBulb, further emphasizing diverging cardiovascular effects of these two incretin hormones.
OBJECTIVE: While existing evidence supports beneficial cardiovascular effects of glucagon-like peptide 1 (GLP-1), emerging studies suggest that glucose-dependent insulinotropic peptide (GIP) and/or signaling via the GIP receptor may have untoward cardiovascular effects. Indeed, recent studies show that fasting physiological GIP levels are associated with total mortality and cardiovascular mortality, and it was suggested that GIP plays a role in pathogenesis of coronary artery disease. We investigated the associations between fasting and postchallenge GIP and GLP-1 concentrations and subclinical atherosclerosis as measured by mean intima-media thickness in the common carotid artery (IMTmeanCCA) and maximal intima-media thickness in the carotid bifurcation (IMTmaxBulb). RESEARCH DESIGN AND METHODS: Participants at reexamination within the Malmö Diet and Cancer-Cardiovascular Cohort study (n = 3,734, mean age 72.5 years, 59.3% women, 10.8% subjects with diabetes, fasting GIP available for 3,342 subjects, fasting GLP-1 available for 3,299 subjects) underwent oral glucose tolerance testing and carotid ultrasound. RESULTS: In linear regression analyses, each 1-SD increment of fasting GIP was associated with increased (per mm) IMTmeanCCA (β = 0.010, P = 0.010) and IMTmaxBulb (β = 0.014; P = 0.040) in models adjusted for known risk factors and glucose metabolism. In contrast, each 1-SD increment of fasting GLP-1 was associated with decreased IMTmaxBulb (per mm, β = -0.016, P = 0.014). These associations remained significant when subjects with diabetes were excluded from analyses. CONCLUSIONS: In a Swedish elderly population, physiologically elevated levels of fasting GIP are associated with increased IMTmeanCCA, while GLP-1 is associated with decreased IMTmaxBulb, further emphasizing diverging cardiovascular effects of these two incretin hormones.
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