Serum Type IV Collagen Concentrations in Diabetic Patients With Microangiopathy as Determined by Enzyme Immunoassay With Monoclonal Antibodies

In long-term diabetes mellitus, thickening of basement membrane in capillaries and small vessels is a characteristic lesion and plays an important role in the progression of diabetic microangiopathy. We have developed a sandwich enzyme immunoassay for human serum type IV collagen peptide with monoclonal antibodies. Previous studies suggested that collagen levels reflect the activity of fibrogenesis in basement membrane. Serum type IV collagen levels were measured in 137 non-insulin-dependent diabetic patients (aged 50–75 yr) with or without clinical signs of retinopathy, nephropathy, and/or neuropathy and 110 healthy subjects (aged 50–75 yr) without serological abnormality. Serum concentrations of type IV collagen were significantly higher (P < 0.01) in diabetic patients (mean ± SE 124.1 ± 4.1 ng/ml) than in healthy subjects (73.9 ± 2.2 ng/ml) and were increased with the prevalence or incidence of diabetic complications. In the patients with diabetic microangiopathy, serum type IV collagen levels became higher as clinical signs worsened. Especially in the patients with diabetic nephropathy, serum type IV collagen levels became higher with elevation of blood urea nitrogen, serum creatinine, and serum β₂-microglobulin but not urinary excretion of β₂- microglobulin and N-acetyl-β-glucosaminidase. These observations indicated that elevation of serum type IV collagen in diabetic nephropathy was related to glomerular filtration dysfunction rather than renal tubular dysfunction. However, the antigen, which can be detected by our assay system, did not exist in urine specimens of healthy subjects, and an intimate relationship was not observed between serum type IV collagen level and serum creatinine level. These results implied that the serum type IV collagen level reflects its increased synthetic activity in basement membrane rather than its reduced clearance rate. The concentration of serum type IV collagen peptide seems to be a useful, noninvasive, reproducible marker for assessment of the activity or progression of diabetic microangiopathy and for evaluation of therapeutic effects.