Matrix Metalloproteinase-8 Activity is Increased in Type 1 Diabetes Children with High-Risk Diabetes HLA and Systemic Inflammation

• Background: Matrix metalloproteinases (MMPs) and myeloperoxidase (MPO) are colocalized to lipid-laden macrophages, and play a central role in initiation and propagation of chronic vascular diseases including atherosclerosis. Prior cross-sectional studies from our centre on children and adolescents with type 1 diabetes suggested possible propensity conferred by diabetes-risk HLA DQ2/8, particularly in an inflammatory milieu, to peripheral vascular dysfunction, an important precursor of atherosclerosis. In the same population, we aimed to assess whether this putative interplay between DQ2/8 and inflammation also reflects into increased activity of MMP and MPO. Methods: Blood pressure, inflammatory, lipid, HbA1c, cyclic guanilate monophospate (cGMP), along with degree of exposure to secondhand tobacco smoke (STS) were determined in 74 children and adolescents with type 1 diabetes at baseline and 1 year later. MMP-8 and MPO levels were measured only at the 2nd time-point. Results: In univariate regression, baseline BMI, HbA1c, CRP(log), and TC/HDL were all predictors of 1-year MMP-2 (p,.05 for all), while exposure to STS, BMI, cGMP, and TC/ HDL predicted levels of MPO (p,.05 for all). The rise in serum MMP-8 was most increased in those with both DQ2/8 and CRP .1 mg/l (p=0.01), but no such difference was noted with regard to MPO. Conclusion: In young patients with type 1 diabetes, increased activities of MMP and MPO appear to relate mainly to dyslipidemia, but inflammation, particularly in those with diabetes-risk HLA, and exposure to tobacco smoke could be important stimuli as well.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Nyckelord

neutrophil collagenase

lipid

hemoglobin A1c

cyclic GMP

matrix metalloproteinase

myeloperoxidase

tobacco smoke

high density lipoprotein

gelatinase A

insulin dependent diabetes mellitus

child

human

risk

diabetes mellitus

HLA system

inflammation

cardiology

Japanese (people)

society

pediatric cardiology

heart surgery

exposure

adolescent

atherosclerosis

blood pressure

population

precursor

dyslipidemia

cross-sectional study

patient

serum

stimulus

vascular disease

macrophage

passive smoking

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