Evidence that upregulation of serum IGF-1 concentration can trigger acceleration of diabetic retinopathy

Background-Acute reduction of chronic hyperglycaemia can accelerate early diabetic retinopathy. In adolescent patients with Mauriac's syndrome, this phenomenon is related to an upregulation of subnormal serum IGF-1 levels. Aim-To obtain longitudinal data on serum IGF-I and retinopathy status in poorly controlled adult insulin dependent (type I) diabetic patients without Mauriac's syndrome, in whom hyperglycaemia is reduced by intensive insulin therapy. Methods-Four patients with chronic severe insulin deficiency and early microangiopathy were studied prospectively. Changes in plasma glucose, HbA(1c), serum IGF-I levels, proteinuria, retinopathy, and clinical status were followed up closely. Results-Reducing hyperglycaemia from >16 mmol/l (equivalent to HbA(1c) >11%) to <10 mmol/l (HbA(1c) <8%) within 5 months increased serum IGF-1. levels by 70-220%. While proteinuria and symptomatic neuropathy regressed, retinopathy progressed from the mild to the severe nonproliferative stage with maculopathy (n=4), and to the proliferative stage (n=1). Laser coagulation was commenced upon the appearance of sight threatening macular oedema (n=4). Conclusion-Upregulation of serum IGF-1 preceding retinal deterioration in these patients suggests a cause-effect relation, consistent with earlier experimental and clinical data.