Glucose-Dependent Insulinotropic Peptide in the High-Normal Range Is Associated With Increased Carotid Intima-Media Thickness

• Published in: Diabetes care Vol. 44; no. 1; pp. 224 - 230
• Main Authors: Jujić, Amra, Nilsson, Peter M, Atabaki-Pasdar, Naeimeh, Dieden, Anna, Tuomi, Tiinamaija, Franks, Paul W, Holst, Jens Juul, Torekov, Signe Sørensen, Ravassa, Susana, Díez, Javier, Persson, Margaretha, Ahlqvist, Emma, Melander, Olle, Gomez, Maria F, Groop, Leif, Magnusson, Martin
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.01.2021
• Subjects: Aged; Arteriosclerosis; Atherosclerosis; Blood Glucose; Cardiovascular disease; Cardiovascular diseases; Carotid artery; Carotid Intima-Media Thickness; Clinical Medicine; Cohort Studies; Coronary artery; Coronary artery disease; Diabetes; Diabetes mellitus; Endocrinology and Diabetes; Endokrinologi och diabetes; Fasting; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-like peptide 1; Glucose; Glucose metabolism; Glucose tolerance; Heart diseases; Hormones; Humans; Klinisk medicin; Laboratory testing; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Mortality; Pathogenesis; Peptides; Physiological effects; Reference Values; Regression analysis; Research design; Risk analysis; Risk factors; Thickness; Ultrasound
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc20-1318

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 (IMT CCA) and maximal intima-media thickness in the carotid bifurcation (IMT Bulb). Participants at reexamination within the Malmö Diet and Cancer-Cardiovascular Cohort study ( = 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. In linear regression analyses, each 1-SD increment of fasting GIP was associated with increased (per mm) IMT CCA (β = 0.010, = 0.010) and IMT Bulb (β = 0.014; = 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 IMT Bulb (per mm, β = -0.016, = 0.014). These associations remained significant when subjects with diabetes were excluded from analyses. In a Swedish elderly population, physiologically elevated levels of fasting GIP are associated with increased IMT CCA, while GLP-1 is associated with decreased IMT Bulb, further emphasizing diverging cardiovascular effects of these two incretin hormones.