Progression of diabetic retinopathy during improved metabolic control may be treated with reduced insulin dosage and/or somatostatin analogue administration – a case report

It is well known that intensified insulin treatment of poorly controlled type 1 diabetic patients may worsen an existing diabetic retinopathy (DR). This observation has been explained by an insulin-induced stimulation of the GH/IGF-I axis. Here, we report on three cases, where the progression of DR during intensified metabolic control was treated with manipulation of insulin therapy and/or by administration of octreotide. Serum concentrations of IGF-I, IGFBP-3, insulin, cystatin C, creatinine, endogenous creatinine clearance and HbA1c-levels were assessed by routine laboratory methods; serum IGF-I bioactivity was estimated by a highly specific kinase receptor activation assay. Visual acuity and retinopathy stage was assessed by established clinical methods including fluorescein angiography. After glycaemic control was improved by intensified insulin therapy, serum IGF-I levels acutely increased. Subsequently, DR progressed to an advanced stage (“florid retinopathy”), with macular edema, and proliferation of new vessels (in two cases). Immediate reduction of insulin dosage and administration of octreotide lowered serum total IGF-I levels (and IGF-I bioactivity as measured in one patient). Subsequently, macular edema resolved partly, and visual acuity improved, allowing laser photocoagulation to be performed. In conclusion, in poorly controlled type 1 diabetic patients, intensified insulin therapy is able to cause florid DR with acute macular edema. These sight-threatening changes may improve by short-term reduction of insulin dosage or by administration of octreotide, and we speculate that this may be related to down-regulation of (serum) IGF-I.