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Glucose-dependent insulinotropic peptide in the high normal range is associated with increased carotid intima-media thickness

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posted on 17.11.2020, 00:14 by Amra Jujić, Peter M Nilsson, Naeimeh Atabaki-Pasdar, Anna Dieden, Tiinamaija Tuomi, Paul W Franks, Jens Juul Holst, Signe Sørensen Torekov, Susana Ravassa, Javier Díez, Margaretha Persson, Emma Ahlqvist, Olle Melander, Maria F Gomez, Leif Groop, Martin Magnusson
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 post-challenge GIP and GLP-1 concentrations and subclinical atherosclerosis as measured by intima-media thickness in the common carotid artery (IMTmeanCCA), and intima-media thickness in the carotid bifurcation (IMTmaxBulb).

Research design and methods: Participants at re-examination within the Malmö Diet and Cancer cardiovascular cohort study (n=3734, mean age 72.5 years; 59.3% women; 10.8% subjects with diabetes; fasting GIP available for 3342 subjects; fasting GLP-1 available for 3299 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.

Conclusion 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.

Funding

This work was supported by these Funding sources: grants from the Swedish Research Council (K2008 – 65X-20 752– 01–3, K2011– 65X-20 752– 04 – 6, 2010-3490), the Lundströms Foundation, the Swedish Heart-Lung Foundation (2010 – 0244; 2013– 0249), ALF government grants (Dnr: 2012/1789). Dr Jujic was funded by Lund University and Region Skane. Drs. Magnusson and Melander were supported by grants from the Swedish Medical Research Council, the Swedish Heart and Lung Foundation, the Medical Faculty of Lund University, Skåne University Hospital, the Albert Påhlsson Research Foundation, the Crafoord Foundation, the Ernhold Lundströms Research Foundation, the Region Skane, the Hulda and Conrad Mossfelt Foundation, the Southwest Skanes Diabetes foundation, the King Gustaf V and Queen Victoria Foundation, the Lennart Hanssons Memorial Fund, Knut and Alice Wallenberg Foundation and the Marianne and Marcus Wallenberg Foundation. Dr Magnusson was also supported by Wallenberg Centre for Molecular Medicine at Lund University. Dr. Nilsson was supported by grants from the Swedish Medical Research Council, the Swedish Heart and Lung Foundation, the Medical Faculty of Lund University, Skåne University Hospital and the Ernhold Lundströms Research Foundation. Dr. Ahlqvist was supported by grants from the Swedish Research Council (2017-02688), Diabetes Wellness Sweden (25-420 PG), the Swedish Heart and Lung Foundation and the Novo Nordisk Foundation (NNF18OC0034408). Dr. Gomez was supported by grants from the Swedish Heart and Lung Foundation (##20190470); the Swedish Research Council (#2018-02837; EXODIAB #2009-1039) and from the Swedish Foundation for Strategic Research (LUDC-IRC #15-0067). Dr Franks and Ms Atabaki-Pasdar were supported by grants from the Swedish Research Council, Heart Lung Foundation, Novo Nordisk Foundation and the European Research Council (CoG-2015_681742_NASCENT). The funders of the study had no role in study design, data collection, data a

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