Glucose-Dependent Insulinotropic Peptide in the High-Normal Range Is Associated With Increased Carotid Intima-Media Thickness
Year: 2020
Type: article
Study design: Observational Study
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.
Source: Diabetes Care
DOI: 10.2337/dc20-1318
Institutions: Lund University, Skåne University Hospital, Malmö University, University of Helsinki, Helsinki University Hospital, Institute for Molecular Medicine Finland, Harvard University, University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Research, Instituto de Salud Carlos III, Centro de Investigación en Red en Enfermedades Cardiovasculares, Navarre Institute of Health Research, Centro de Investigación Médica Aplicada, Universidad de Navarra, Clinica Universidad de Navarra, North-West University
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Eli Lilly and Company, Southwest Skanes Diabetes Foundation, Stiftelsen för Strategisk Forskning, Crafoordska Stiftelsen, Lunds Universitet, Lundbeckfonden, Hjärt-Lungfonden, Knut och Alice Wallenbergs Stiftelse, Novo Nordisk, Vetenskapsrådet, Lund University Medical Faculty Foundation, Direktör Albert Påhlssons Stiftelse, Sydvästra Skånes Diabetesförening, C. F. Lundströms Stiftelse, Novo Nordisk Fonden, Ernhold Lundströms stiftelse, Hulda och E Conrad Mossfelts Stiftelse för Vetenskaplig Forskning Inom Hjärt- och Kärlsjukdomarnas Område, Region Skåne, Skånes universitetssjukhus, Marcus och Amalia Wallenbergs minnesfond, Medical Research Council, Wallenberg Centre for Molecular and Translational Medicine, H2020 European Research Council
Awards: G1478260506, General and targeted approaches to unraveling the molecular causes of type 2 diabetes, G2004031785, G2322197998, G2349186604, G263730981, G2787057996, G3191884797, Subclassification of type 2 diabetes - new genes and new mechanisms, G3883017987, G3884363820, G4693205679, G4924622555, G5976813381, G6307800215, G6711065194, G6922923410, G712881263, LUDC-IRC för individanpassad medicin i diabetes, Novel molecular mechanisms underlying diabetic complications, G8392101073, G8543011816
OpenAlex ID: W3105350559