Why some cases of retinopathy worsen when diabetic control improves

In the 1970s Engerman et al showed that strict control of diabetes could prevent the development of retinopathy in diabetic dogs.1 When close monitoring of glycaemia and methods of giving frequent insulin injections became possible in routine practice clinicians had great expectations that similarly strict control in humans could prevent the development of diabetic retinopathy and arrest or even reverse early lesions. These expectations were dashed, however, when it became clear that tightening control in patients with existing retinopathy could make the lesions worse.2 This normoglycaemic re-entry phenomenon has puzzled clinicians,3 and, although there is still much to learn about its mechanism, it is becoming clearer how to manage it. Early findings that patients with varying degrees of retinopathy suffered a paradoxical worsening of their lesions as their diabetic control improved2 3 4 5 6 have been confirmed in a recent large study of non-insulin dependent diabetics started on insulin.7 But even before …