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Plasma levels of matrix metalloproteinase-2, -3, -10, and tissue inhibitor of metalloproteinase-1 are associated with vascular complications in patients with type 1 diabetes: the EURODIAB Prospective Complications Study.

Peeters SA, Engelen L, Buijs J, Chaturvedi N, Fuller JH, Schalkwijk CG, Stehouwer CD, EURODIAB Prospective Complications Study Gro - Cardiovasc Diabetol (2015)

Bottom Line: Higher plasma levels of MMP-2, MMP-3, MMP-10 and TIMP-1 were associated with higher levels of albuminuria (p-trends were 0.028, 0.004, 0.005 and 0.001, respectively).Severity of retinopathy was significantly associated with higher levels of MMP-2 (p-trend = 0.017).These associations remained significant after further adjustment for markers of LGI and ED.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Impaired regulation of extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may contribute to vascular complications in patients with type 1 diabetes. We investigated associations between plasma MMP-1, -2, -3, -9, -10 and TIMP-1, and cardiovascular disease (CVD) or microvascular complications in type 1 diabetic patients. We also evaluated to which extent these associations could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED).

Methods: 493 type 1 diabetes patients (39.5 ± 9.9 years old, 51% men) from the EURODIAB Prospective Complications Study were included. Linear regression analysis was applied to investigate differences in plasma levels of MMP-1, -2, -3, -9, -10, and TIMP-1 between patients with and without CVD, albuminuria or retinopathy. All analyses were adjusted for age, sex, duration of diabetes, Hba1c and additionally for other cardiovascular risk factors including LGI and ED.

Results: Patients with CVD (n = 118) showed significantly higher levels of TIMP-1 [β = 0.32 SD (95%CI: 0.12; 0.52)], but not of MMPs, than patients without CVD (n = 375). Higher plasma levels of MMP-2, MMP-3, MMP-10 and TIMP-1 were associated with higher levels of albuminuria (p-trends were 0.028, 0.004, 0.005 and 0.001, respectively). Severity of retinopathy was significantly associated with higher levels of MMP-2 (p-trend = 0.017). These associations remained significant after further adjustment for markers of LGI and ED.

Conclusions: These data support the hypothesis that impaired regulation of matrix remodeling by actions of MMP-2, -3 and-10 and TIMP-1 contributes to the pathogenesis of vascular complications in type 1 diabetes.

No MeSH data available.


Related in: MedlinePlus

Associations between plasma levels of MMPs, TIMP-1 and CVD. Point estimates and 95% confidence intervals show the difference in plasma levels of lnMMP or TIMP-1 (in SD) in patients with vs. those without CVD resulting from a multivariable regression model including all cardiovascular risk factors, albuminuria and retinopathy (model 2).
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Fig1: Associations between plasma levels of MMPs, TIMP-1 and CVD. Point estimates and 95% confidence intervals show the difference in plasma levels of lnMMP or TIMP-1 (in SD) in patients with vs. those without CVD resulting from a multivariable regression model including all cardiovascular risk factors, albuminuria and retinopathy (model 2).

Mentions: Significantly higher plasma levels of TIMP-1 [β = 0.27 SD (95%CI: 0.06; 0.48)] were observed in individuals with CVD (n = 118) as compared to those without, after adjustment for age, sex, duration of diabetes and HbA1c (Additional file 1: Table S1, Model 1). The association became even stronger [0.32 (0.12; 0.52)] after further adjustment for other cardiovascular risk factors, albuminuria and retinopathy (Figure 1; Additional file 1: Table S1, Model 2). In contrast, MMP-1, MMP-2, MMP-3, MMP-9 and MMP-10 did not differ between groups.Figure 1


Plasma levels of matrix metalloproteinase-2, -3, -10, and tissue inhibitor of metalloproteinase-1 are associated with vascular complications in patients with type 1 diabetes: the EURODIAB Prospective Complications Study.

Peeters SA, Engelen L, Buijs J, Chaturvedi N, Fuller JH, Schalkwijk CG, Stehouwer CD, EURODIAB Prospective Complications Study Gro - Cardiovasc Diabetol (2015)

Associations between plasma levels of MMPs, TIMP-1 and CVD. Point estimates and 95% confidence intervals show the difference in plasma levels of lnMMP or TIMP-1 (in SD) in patients with vs. those without CVD resulting from a multivariable regression model including all cardiovascular risk factors, albuminuria and retinopathy (model 2).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4355971&req=5

Fig1: Associations between plasma levels of MMPs, TIMP-1 and CVD. Point estimates and 95% confidence intervals show the difference in plasma levels of lnMMP or TIMP-1 (in SD) in patients with vs. those without CVD resulting from a multivariable regression model including all cardiovascular risk factors, albuminuria and retinopathy (model 2).
Mentions: Significantly higher plasma levels of TIMP-1 [β = 0.27 SD (95%CI: 0.06; 0.48)] were observed in individuals with CVD (n = 118) as compared to those without, after adjustment for age, sex, duration of diabetes and HbA1c (Additional file 1: Table S1, Model 1). The association became even stronger [0.32 (0.12; 0.52)] after further adjustment for other cardiovascular risk factors, albuminuria and retinopathy (Figure 1; Additional file 1: Table S1, Model 2). In contrast, MMP-1, MMP-2, MMP-3, MMP-9 and MMP-10 did not differ between groups.Figure 1

Bottom Line: Higher plasma levels of MMP-2, MMP-3, MMP-10 and TIMP-1 were associated with higher levels of albuminuria (p-trends were 0.028, 0.004, 0.005 and 0.001, respectively).Severity of retinopathy was significantly associated with higher levels of MMP-2 (p-trend = 0.017).These associations remained significant after further adjustment for markers of LGI and ED.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Impaired regulation of extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may contribute to vascular complications in patients with type 1 diabetes. We investigated associations between plasma MMP-1, -2, -3, -9, -10 and TIMP-1, and cardiovascular disease (CVD) or microvascular complications in type 1 diabetic patients. We also evaluated to which extent these associations could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED).

Methods: 493 type 1 diabetes patients (39.5 ± 9.9 years old, 51% men) from the EURODIAB Prospective Complications Study were included. Linear regression analysis was applied to investigate differences in plasma levels of MMP-1, -2, -3, -9, -10, and TIMP-1 between patients with and without CVD, albuminuria or retinopathy. All analyses were adjusted for age, sex, duration of diabetes, Hba1c and additionally for other cardiovascular risk factors including LGI and ED.

Results: Patients with CVD (n = 118) showed significantly higher levels of TIMP-1 [β = 0.32 SD (95%CI: 0.12; 0.52)], but not of MMPs, than patients without CVD (n = 375). Higher plasma levels of MMP-2, MMP-3, MMP-10 and TIMP-1 were associated with higher levels of albuminuria (p-trends were 0.028, 0.004, 0.005 and 0.001, respectively). Severity of retinopathy was significantly associated with higher levels of MMP-2 (p-trend = 0.017). These associations remained significant after further adjustment for markers of LGI and ED.

Conclusions: These data support the hypothesis that impaired regulation of matrix remodeling by actions of MMP-2, -3 and-10 and TIMP-1 contributes to the pathogenesis of vascular complications in type 1 diabetes.

No MeSH data available.


Related in: MedlinePlus