A pilot study of chronic recombinant interferon-alfa 2a for diabetic proliferative retinopathy: metabolic effects and...

The objective of this study was to evaluate the metabolic effects and opthalmologic effects of alpha-interferon therapy in diabetes mellitus patients with proliferative diabetic retinopathy (PDR). Three volunteer patients [insulin-dependent diabetes mellitus (IDDM), insulin requiring non-insulin-dependent diabetes mellitus (NIDDM), and maturity onset diabetes of the young (MODY)] threatened with blindness due to progressive PDR were treated with alpha interferon for 4 months and were evaluated at intervals of 1-2 weeks to monitor the drug effects on carbohydrate tolerance and possible beneficial therapeutic effects on the preexisting PDR. Metabolic studies included basal and postsustacal glucose, c-peptide and glucagon, fasting serum cortisol, free fatty acids, growth hormone, insulin-like growth factor-1, and urinary microalbumin excretion. Ophthalmologic studies included visual acuity, slit lamp examination, gonioscopy, fluorescein angiography, and standard colored fundus photographs. In all subjects, hyperglycemia worsened with duration of increasing dosage of interferon therapy, requiring progressively higher daily insulin requirements of 17%-68% above pretreatment values. Lowered levels of stimulated C-peptide were observed in the NIDDM and MODY subjects. The counterregulatory hormones (cortisol, growth hormone, and glucagon) were elevated during the 4 months of interferon therapy. In all subjects, visual acuity appeared to stabilize. No new retinal hemorrhages occurred during the 4 months of interferon administration, although all subjects experienced hemorrhage within 6 weeks of termination of the drug. Although only three subjects were investigated, the 1-2 week frequency of metabolic and opthalmologic studies permit some conclusions. The metabolic effects of alpha interferon in our diabetic subjects were consistent worsening of carbohydrate tolerance associated with impaired beta-cell secretion and increased insulin resistance. The extensive opthalmologic investigation suggested protection from retinal hemorrhage while receiving interferon, but further studies are indicated to validate these proposed and antiangiogenic properties.