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Paul Franks

Paul Franks

Principal investigator

Paul Franks

Glucose-dependent insulinotropic peptide and risk of cardiovascular events and mortality : a prospective study

Author

  • Amra Jujić
  • Naeimeh Atabaki-Pasdar
  • Peter M Nilsson
  • Peter Almgren
  • Liisa Hakaste
  • Tiinamaija Tuomi
  • Lisa M Berglund
  • Paul W Franks
  • Jens J Holst
  • Rashmi B Prasad
  • Signe S Torekov
  • Susana Ravassa
  • Javier Díez
  • Margaretha Persson
  • Olle Melander
  • Maria F Gomez
  • Leif Groop
  • Emma Ahlqvist
  • Martin Magnusson

Summary, in English

AIMS/HYPOTHESIS: Evidence that glucose-dependent insulinotropic peptide (GIP) and/or the GIP receptor (GIPR) are involved in cardiovascular biology is emerging. We hypothesised that GIP has untoward effects on cardiovascular biology, in contrast to glucagon-like peptide 1 (GLP-1), and therefore investigated the effects of GIP and GLP-1 concentrations on cardiovascular disease (CVD) and mortality risk.

METHODS: GIP concentrations were successfully measured during OGTTs in two independent populations (Malmö Diet Cancer-Cardiovascular Cohort [MDC-CC] and Prevalence, Prediction and Prevention of Diabetes in Botnia [PPP-Botnia]) in a total of 8044 subjects. GLP-1 (n = 3625) was measured in MDC-CC. The incidence of CVD and mortality was assessed via national/regional registers or questionnaires. Further, a two-sample Mendelian randomisation (2SMR) analysis between the GIP pathway and outcomes (coronary artery disease [CAD] and myocardial infarction) was carried out using a GIP-associated genetic variant, rs1800437, as instrumental variable. An additional reverse 2SMR was performed with CAD as exposure variable and GIP as outcome variable, with the instrumental variables constructed from 114 known genetic risk variants for CAD.

RESULTS: In meta-analyses, higher fasting levels of GIP were associated with risk of higher total mortality (HR[95% CI] = 1.22 [1.11, 1.35]; p = 4.5 × 10-5) and death from CVD (HR[95% CI] 1.30 [1.11, 1.52]; p = 0.001). In accordance, 2SMR analysis revealed that increasing GIP concentrations were associated with CAD and myocardial infarction, and an additional reverse 2SMR revealed no significant effect of CAD on GIP levels, thus confirming a possible effect solely of GIP on CAD.

CONCLUSIONS/INTERPRETATION: In two prospective, community-based studies, elevated levels of GIP were associated with greater risk of all-cause and cardiovascular mortality within 5-9 years of follow-up, whereas GLP-1 levels were not associated with excess risk. Further studies are warranted to determine the cardiovascular effects of GIP per se.

Department/s

  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Cardiovascular Research - Hypertension
  • Genetic and Molecular Epidemiology
  • Internal Medicine - Epidemiology
  • EpiHealth: Epidemiology for Health
  • Diabetes - Cardiovascular Disease
  • Genomics, Diabetes and Endocrinology
  • Diabetic Complications
  • Department of Clinical Sciences, Malmö
  • WCMM-Wallenberg Centre for Molecular Medicine

Publishing year

2020-05

Language

English

Pages

1043-1054

Publication/Series

Diabetologia

Volume

63

Issue

5

Document type

Journal article

Publisher

Springer

Topic

  • Cardiac and Cardiovascular Systems
  • Endocrinology and Diabetes

Status

Published

Research group

  • Cardiovascular Research - Hypertension
  • Genetic and Molecular Epidemiology
  • Internal Medicine - Epidemiology
  • Diabetes - Cardiovascular Disease
  • Genomics, Diabetes and Endocrinology
  • Diabetic Complications

ISBN/ISSN/Other

  • ISSN: 1432-0428