To define risk factors and markers associated with proliferative retinopathy (PR), we compared 44 insulindependent diabetic patients with PR with 45 matched patients without advanced retinopathy (NR). Glycemic control assessed by HbA1 measurements from 5 yr preceding diagnosis of PR was significantly worse than in NR patients. The NR patients had more frequently been treated with multiple daily insulin injections than the PR patients. About half of the PR patients had Albustix-positive proteinuria, and these patients were further characterized by an abnormal lipid profile in plasma and increased frequency of cardiovascular disease. In contrast, PR patients without proteinuria did not differ from NR patients in these variables. Sensorimotor and autonomic neuropathy were twice as frequent in the PR than in the NR group. There was no correlation between anti-insulin antibody titer, immune complexes, and the presence of PR, but T-lymphocyte response to different stimuli was slightly reduced in the PR patients. The anti-insulin-antibody titer correlated with duration of diabetes in the NR but not the PR group. The frequency of HLA-DRw8 was slightly higher in the PR group than in the NR group (16 vs. 0%, NS), but we could not confirm the previously suggested association between HLA-DR4 and PR. Serum C4 levels were low in the diabetics but did not differ between PR patients without proteinuria and NR patients.

In conclusion, poor glycemic control was clearly associated with PR in this study, and attempts to prevent this hazardous complication should include means to improve insulin therapy. We did not find support for the view that susceptibility to PR is associated with any known HLA antigen(s). Although cell-mediated immunity was slightly impaired in the PR patients, the elucidation of the role of immunologic factors in the pathogenesis of PR requires a long-term prospective Study.

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