Continued progression of retinopathy despite spontaneous recovery to normoglycemia in a long-term study of streptozotocin-induced diabetes in rats

Background: This long-term (2.3 years) study determines the temporal relati onship between systemic glucose levels and the progression of diabetic reti nopathy during the natural course of streptozotocin-induced diabetes in rat s. Methods: Of 367 rats, 200 were randomly assigned into a group injected with streptozotocin (50 mg.kg(-1)) and 167 into a control group. Subsets of the rats were killed at 6, 28, 40, 65, 90 and >100 weeks post induction to all ow the severity of retinopathy to be assessed quantitatively and qualitativ ely by trypsin digests of the retinal vasculature. Concurrently blood gluco se, body weight and death rate were monitored, Results: Three glycemic phases were observed in the streptozotocin rats. In phase 1 (0 to 36-40 weeks) hyperglycemia was established and maintained. I n phase 2 (36-40 to 84-90 weeks) normoglycemia was restored, and maintained during phase 3 (84-90 to 120 weeks). Control rats were normoglycemic throu ghout. The retinal microangiopathy was marked at 28 weeks during phase 1, d eveloped more slowly in phase 2 and continued to worsen with loss of capill aries in all retinas and saccular microaneurysms present in 50% of retinas in phase 3, Cumulative death rate in streptozotocin rats also followed thre e phases, with maximum vulnerability occurring between 28 and 40 weeks. Bod y weight was significantly lower in streptozotocin rats throughout, increas ing slowly in phase 1, then more rapidly during and after spontaneous glyce mic recovery. Conclusion: The worsening retinopathy, despite sustained recovery to normog lycemia, implies that good glucose control alone does not stop the progress ion of the retinal microangiopathy at this late stage.