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To disclose the chronological changes prior to the manifestation of diabetic retinopathy (DR), we analyzed the time course of biological markers among apparently healthy diabetic subjects in a case-control study of 21,579 adults who had undergone comprehensive health examinations for > or = 10 years. We identified 54 cases who had newly developed DR, and selected 108 adults without fundus abnormalities, matching them for sex, age, and fasting plasma glucose (FPG) at the onset of the patient group's retinopathy as a referent group from the same population. In a multivariate analysis, a high average FPG (> 175 mg/dl) and a final-year FPG reduction (< -3%) were significantly associated with a 5.4 (95% CI, 1.8-15.7)- and 5.0 (95% CI, 1.0-24.7)-fold increased risk of DR, respectively. Thus, we surmised that sustained hyperglycemia and a subsequent drop in FPG might promote retinopathy in non-insulin dependent diabetes mellitus.

Newly developed diabetic retinopathy and its preceding changes in biological markers.