Biochemical markers of type III and I collagen: association with retinopathy and neuropathy in type 1 diabetic subjects.
OBJECTIVE
Connective tissue alterations may contribute to the development of diabetic long-term complications in eyes, kidneys and peripheral nerves. Collagen deposition may be increased in micro- and macrovascular disease in diabetic subjects. We tested whether biochemical markers of type III and I collagen metabolism are associated with retinopathy and neuropathy in Type 1 diabetes.


METHODS
A total of 28 patients, mean age 43.4 +/- 9.5 (sd) and duration of diabetes 25.2 +/- 9.7 years, were studied. Stereoscopic colour fundus photographs were taken for assessment of retinopathy which was classified as no, background or proliferative. Concentrations of aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in serum and urinary excretion of cross-linked N-telopeptides of type I collagen (NTX) and deoxypyridinoline crosslinks (DPyr) into urine were measured.


RESULTS
Average serum PIIINP was higher in subjects with proliferative (3.2 +/- 1.1 microg/l) than without proliferative retinopathy (2.5 +/- 0.6 microg/l) (P = 0.03). Average serum PICP was higher in subjects without retinopathy (181.7 +/- 19.5 microg/l) than in subjects with background retinopathy (132.1 +/- 42.7 microg/l) (P = 0.02). Concentrations of other collagen markers were not different in subjects with or without retinopathy. No association between collagen markers and neuropathy was found.


CONCLUSIONS
The increased synthesis of type III collagen, reflecting deposition of matrix and basement membrane connective tissue, may be involved in the pathogenesis of proliferative retinopathy in Type 1 diabetic subjects. On the other hand, we observed decreased synthesis of Type I collagen, which can result in weakened vascular integrity in subjects with retinopathy.
Arkkila
P E
PE
Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland. perttu.arkkila@hus.fi
Rönnemaa
T
T
Koskinen
P J
PJ
Kantola
I M
IM
Seppänen
E
E
Viikari
J S
JS
D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D003094:Collagen / Q000097:blood; D024042:Collagen Type I / Q000097:blood*; D024061:Collagen Type III / Q000097:blood*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology / Q000652:urine; D003929:Diabetic Neuropathies / Q000453:epidemiology*; D003930:Diabetic Retinopathy / Q000453:epidemiology*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood
D015415:Biomarkers; D003094:Collagen; D024042:Collagen Type I; D024061:Collagen Type III; D006442:Glycated Hemoglobin; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C042813:procollagen type I carboxy terminal peptide