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

Abstract

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-1 and retinopathy status in poorly controlled adult insulin dependent (type 1) 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-1 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 non-proliferative 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.