Glucose-dependent insulinotropic peptide and risk of cardiovascular events and mortality: a prospective study
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Glucose-dependent insulinotropic peptide and risk of cardiovascular events and mortality : a prospective study. / Jujic, Amra; Atabaki-Pasdar, Naeimeh; Nilsson, Peter M.; Almgren, Peter; Hakaste, Liisa; Tuomi, Tiinamaija; Berglund, Lisa M.; Franks, Paul W.; Holst, Jens J.; Prasad, Rashmi B.; Torekov, Signe S.; Ravassa, Susana; Diez, Javier; Persson, Margaretha; Melander, Olle; Gomez, Maria F.; Groop, Leif; Ahlqvist, Emma; Magnusson, Martin.
I: Diabetologia, Bind 63, Nr. 5, 05.2020, s. 1043-1054.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Glucose-dependent insulinotropic peptide and risk of cardiovascular events and mortality
T2 - a prospective study
AU - Jujic, Amra
AU - Atabaki-Pasdar, Naeimeh
AU - Nilsson, Peter M.
AU - Almgren, Peter
AU - Hakaste, Liisa
AU - Tuomi, Tiinamaija
AU - Berglund, Lisa M.
AU - Franks, Paul W.
AU - Holst, Jens J.
AU - Prasad, Rashmi B.
AU - Torekov, Signe S.
AU - Ravassa, Susana
AU - Diez, Javier
AU - Persson, Margaretha
AU - Melander, Olle
AU - Gomez, Maria F.
AU - Groop, Leif
AU - Ahlqvist, Emma
AU - Magnusson, Martin
PY - 2020/5
Y1 - 2020/5
N2 - 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 (Malmo 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 x 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.
AB - 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 (Malmo 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 x 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.
KW - Cardiovascular
KW - Cardiovascular events
KW - Coronary artery disease
KW - GIP
KW - GLP-1
KW - Glucagon-like peptide 1
KW - Glucose-dependent insulinotropic peptide
KW - Mendelian randomisation
KW - Mortality
KW - MENDELIAN RANDOMIZATION ANALYSES
KW - POLYPEPTIDE
KW - OSTEOPONTIN
KW - LIRAGLUTIDE
KW - PREVALENCE
KW - DIAGNOSIS
KW - OUTCOMES
KW - LOCI
U2 - 10.1007/s00125-020-05093-9
DO - 10.1007/s00125-020-05093-9
M3 - Journal article
C2 - 31974732
VL - 63
SP - 1043
EP - 1054
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 5
ER -
ID: 247216154