Increased plasma markers of inflammation and endothelial dysfunction and their association with microvascular complications in Type 1 diabetic patients without clinically manifest macroangiopathy.
OBJECTIVE
To evaluate whether plasma biomarkers of inflammation and endothelial dysfunction differed in Type 1 diabetic patients as compared with those in non-diabetic subjects, and to examine the association of these biomarkers with early stages of microvascular complications.


METHODS
Plasma biomarkers of inflammation [fibrinogen, hs-C-reactive protein (hs-CRP)] and endothelial dysfunction [von Willebrand factor (v-WF), intercellular adhesion molecule-1, plasminogen activator inhibitor-1 (PAI-1) activity] were measured in 88 non-smoking young patients with Type 1 diabetes without clinical macrovascular disease and in 40 healthy controls.


RESULTS
Plasma levels of hs-CRP, fibrinogen, v-WF, soluble intracellular adhesion molecule-1 (sICAM-1) and PAI-1 activity were markedly higher (P < 0.01 or less) in Type 1 diabetic patients than in healthy controls; these results were essentially unchanged when healthy controls were compared with patients without complications. After stratification by microvascular complication status, plasma biomarkers of inflammation and endothelial dysfunction were significantly increased in those with more advanced disease compared with those with early complications or without complications, respectively. However, while the significant differences in these biomarkers were little affected by adjustment for sex, age, BMI and blood pressure values, they were totally abolished after additional adjustment for diabetes duration and glycaemic control.


CONCLUSIONS
These results indicate that in Type 1 diabetes there is a subclinical, chronic inflammation which is, at least partly, independent of clinically manifest macro- and microvascular complications, smoking or other traditional cardiovascular risk factors; this subclinical inflammation is closely correlated to the magnitude and duration of hyperglycaemia.
Targher
G
G
Department of Internal Medicine, Sacro Cuore Hospital, Negrar, Italy. targher@sacrocuore.it
Bertolini
L
L
Zoppini
G
G
Zenari
L
L
Falezza
G
G
D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism*; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D048909:Diabetes Complications; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005340:Fibrinogen / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism*; D008297:Male; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000032:analysis / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000032:analysis / Q000378:metabolism*; D014841:von Willebrand Factor / Q000032:analysis / Q000378:metabolism*
D015415:Biomarkers; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen; D002097:C-Reactive Protein