The IGF system in patients with type 2 diabetes: Associations with markers of cardiovascular target organ damage

Rikke Hjortebjerg*, Esben Laugesen, Pernille Hoyem, Claus Oxvig, Brian Stausbøl-Gron, Søren T. Knudsen, Won Y. Kim, Per L. Poulsen, Troels K. Hansen, Mette Bjerre, Jan Frystyk

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Objective: Perturbations in the insulin-like growth factor (IGF) system may contribute to the accelerated cardiovascular disease (CVD) that occurs in patients with type 2 diabetes (T2D). However, it remains unknown whether the IGF system is also involved in the development of early, subclinical CVD. We characterised the IGF system in T2D patients and matched controls and examined the associations with markers of subclinical target organ damage. Methods: The study included 99 patients with recently diagnosed T2D and 99 age- and sex-matched controls. IGF-1 and IGFBP-1 to -4 were measured by immunoassays, as were pregnancy-associated plasma protein-A (PAPP-A) and the PAPP-A-generated N-terminal (NT) and C-terminal (CT) IGFBP-4 fragments, which are novel CVD risk markers. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV). Cerebral white matter lesions (WMLs) and carotid artery remodelling were determined by MRI. Results: After multivariate adjustments, patients with T2D had lower concentrations of IGFBP-2, IGFBP-4, NT- and CT-IGFBP-4, when compared with controls. IGFBP-2 was inversely correlated to PWV in all subjects in multivariate analysis (P < 0.05), and IGFBP-3 was inversely associated with severity of WMLs (P < 0.05). The NT-IGFBP-4 fragment was associated with the degree of carotid artery remodelling among all subjects (regression coefficient (95% CI): 2.95 (0.70, 5.16), P = 0.011). Levels of NT- and CT-IGFBP-4 were reduced in T2D patients receiving metformin compared to those in controls and patients not receiving metformin. Conclusions: Even in recently diagnosed and well-controlled T2D patients, IGF protein levels are altered and associated with CVD risk factors.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Endocrinology
Vol/bind176
Udgave nummer5
Sider (fra-til)521-531
Antal sider11
ISSN0804-4643
DOI
StatusUdgivet - 1. maj 2017
Udgivet eksterntJa

Fingeraftryk

Insulin-Like Growth Factor Binding Protein 4
Type 2 Diabetes Mellitus
Pregnancy-Associated Plasma Protein-A
Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor Binding Protein 3
Vascular Stiffness
Immunoassay
Multivariate Analysis
Proteins

Citer dette

Hjortebjerg, Rikke ; Laugesen, Esben ; Hoyem, Pernille ; Oxvig, Claus ; Stausbøl-Gron, Brian ; Knudsen, Søren T. ; Kim, Won Y. ; Poulsen, Per L. ; Hansen, Troels K. ; Bjerre, Mette ; Frystyk, Jan. / The IGF system in patients with type 2 diabetes : Associations with markers of cardiovascular target organ damage. I: European Journal of Endocrinology. 2017 ; Bind 176, Nr. 5. s. 521-531.
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title = "The IGF system in patients with type 2 diabetes: Associations with markers of cardiovascular target organ damage",
abstract = "Objective: Perturbations in the insulin-like growth factor (IGF) system may contribute to the accelerated cardiovascular disease (CVD) that occurs in patients with type 2 diabetes (T2D). However, it remains unknown whether the IGF system is also involved in the development of early, subclinical CVD. We characterised the IGF system in T2D patients and matched controls and examined the associations with markers of subclinical target organ damage. Methods: The study included 99 patients with recently diagnosed T2D and 99 age- and sex-matched controls. IGF-1 and IGFBP-1 to -4 were measured by immunoassays, as were pregnancy-associated plasma protein-A (PAPP-A) and the PAPP-A-generated N-terminal (NT) and C-terminal (CT) IGFBP-4 fragments, which are novel CVD risk markers. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV). Cerebral white matter lesions (WMLs) and carotid artery remodelling were determined by MRI. Results: After multivariate adjustments, patients with T2D had lower concentrations of IGFBP-2, IGFBP-4, NT- and CT-IGFBP-4, when compared with controls. IGFBP-2 was inversely correlated to PWV in all subjects in multivariate analysis (P < 0.05), and IGFBP-3 was inversely associated with severity of WMLs (P < 0.05). The NT-IGFBP-4 fragment was associated with the degree of carotid artery remodelling among all subjects (regression coefficient (95{\%} CI): 2.95 (0.70, 5.16), P = 0.011). Levels of NT- and CT-IGFBP-4 were reduced in T2D patients receiving metformin compared to those in controls and patients not receiving metformin. Conclusions: Even in recently diagnosed and well-controlled T2D patients, IGF protein levels are altered and associated with CVD risk factors.",
author = "Rikke Hjortebjerg and Esben Laugesen and Pernille Hoyem and Claus Oxvig and Brian Stausb{\o}l-Gron and Knudsen, {S{\o}ren T.} and Kim, {Won Y.} and Poulsen, {Per L.} and Hansen, {Troels K.} and Mette Bjerre and Jan Frystyk",
year = "2017",
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Hjortebjerg, R, Laugesen, E, Hoyem, P, Oxvig, C, Stausbøl-Gron, B, Knudsen, ST, Kim, WY, Poulsen, PL, Hansen, TK, Bjerre, M & Frystyk, J 2017, 'The IGF system in patients with type 2 diabetes: Associations with markers of cardiovascular target organ damage', European Journal of Endocrinology, bind 176, nr. 5, s. 521-531. https://doi.org/10.1530/EJE-16-0940

The IGF system in patients with type 2 diabetes : Associations with markers of cardiovascular target organ damage. / Hjortebjerg, Rikke; Laugesen, Esben; Hoyem, Pernille; Oxvig, Claus; Stausbøl-Gron, Brian; Knudsen, Søren T.; Kim, Won Y.; Poulsen, Per L.; Hansen, Troels K.; Bjerre, Mette; Frystyk, Jan.

I: European Journal of Endocrinology, Bind 176, Nr. 5, 01.05.2017, s. 521-531.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - The IGF system in patients with type 2 diabetes

T2 - Associations with markers of cardiovascular target organ damage

AU - Hjortebjerg, Rikke

AU - Laugesen, Esben

AU - Hoyem, Pernille

AU - Oxvig, Claus

AU - Stausbøl-Gron, Brian

AU - Knudsen, Søren T.

AU - Kim, Won Y.

AU - Poulsen, Per L.

AU - Hansen, Troels K.

AU - Bjerre, Mette

AU - Frystyk, Jan

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Objective: Perturbations in the insulin-like growth factor (IGF) system may contribute to the accelerated cardiovascular disease (CVD) that occurs in patients with type 2 diabetes (T2D). However, it remains unknown whether the IGF system is also involved in the development of early, subclinical CVD. We characterised the IGF system in T2D patients and matched controls and examined the associations with markers of subclinical target organ damage. Methods: The study included 99 patients with recently diagnosed T2D and 99 age- and sex-matched controls. IGF-1 and IGFBP-1 to -4 were measured by immunoassays, as were pregnancy-associated plasma protein-A (PAPP-A) and the PAPP-A-generated N-terminal (NT) and C-terminal (CT) IGFBP-4 fragments, which are novel CVD risk markers. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV). Cerebral white matter lesions (WMLs) and carotid artery remodelling were determined by MRI. Results: After multivariate adjustments, patients with T2D had lower concentrations of IGFBP-2, IGFBP-4, NT- and CT-IGFBP-4, when compared with controls. IGFBP-2 was inversely correlated to PWV in all subjects in multivariate analysis (P < 0.05), and IGFBP-3 was inversely associated with severity of WMLs (P < 0.05). The NT-IGFBP-4 fragment was associated with the degree of carotid artery remodelling among all subjects (regression coefficient (95% CI): 2.95 (0.70, 5.16), P = 0.011). Levels of NT- and CT-IGFBP-4 were reduced in T2D patients receiving metformin compared to those in controls and patients not receiving metformin. Conclusions: Even in recently diagnosed and well-controlled T2D patients, IGF protein levels are altered and associated with CVD risk factors.

AB - Objective: Perturbations in the insulin-like growth factor (IGF) system may contribute to the accelerated cardiovascular disease (CVD) that occurs in patients with type 2 diabetes (T2D). However, it remains unknown whether the IGF system is also involved in the development of early, subclinical CVD. We characterised the IGF system in T2D patients and matched controls and examined the associations with markers of subclinical target organ damage. Methods: The study included 99 patients with recently diagnosed T2D and 99 age- and sex-matched controls. IGF-1 and IGFBP-1 to -4 were measured by immunoassays, as were pregnancy-associated plasma protein-A (PAPP-A) and the PAPP-A-generated N-terminal (NT) and C-terminal (CT) IGFBP-4 fragments, which are novel CVD risk markers. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV). Cerebral white matter lesions (WMLs) and carotid artery remodelling were determined by MRI. Results: After multivariate adjustments, patients with T2D had lower concentrations of IGFBP-2, IGFBP-4, NT- and CT-IGFBP-4, when compared with controls. IGFBP-2 was inversely correlated to PWV in all subjects in multivariate analysis (P < 0.05), and IGFBP-3 was inversely associated with severity of WMLs (P < 0.05). The NT-IGFBP-4 fragment was associated with the degree of carotid artery remodelling among all subjects (regression coefficient (95% CI): 2.95 (0.70, 5.16), P = 0.011). Levels of NT- and CT-IGFBP-4 were reduced in T2D patients receiving metformin compared to those in controls and patients not receiving metformin. Conclusions: Even in recently diagnosed and well-controlled T2D patients, IGF protein levels are altered and associated with CVD risk factors.

U2 - 10.1530/EJE-16-0940

DO - 10.1530/EJE-16-0940

M3 - Journal article

C2 - 28179448

AN - SCOPUS:85015591740

VL - 176

SP - 521

EP - 531

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 5

ER -