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 micro-angiopathy were studied prospectively. Changes in plasma glucose, HbA1c, serum IGF-1 levels, proteinuria, retinopathy, and clinical status were followed up closely.

Results: Reducing hyperglycaemia from > 16 mmol/l (equivalent to HbA1c > 11%) to < 10 mmol/l (HbA1c < 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.

Figure 1

Fundus photograph of the right eye of patient CH. Start of improved diabetes control. Retinopathy level 1 (minimal non-proliferative retinopathy⁹); serum IGF-1 concentration 167 ng/ml.

Figure 2

Fundus photograph of the right eye of patient CH 1 month after improving diabetes control. Retinopathy level 1, serum IGF-1 concentration 282 ng/ml.

Figure 3

Fundus photograph of the right eye of patient CH 5 months after improving diabetes control. Retinopathy level 2 (moderate non-proliferative retinopathy⁹); serum IGF-1 level 284 ng/ml.

Figure 4

Fundus photograph of the right eye of patient CH 9 months after improving diabetes control. Retinopathy level 5 (proliferative retinopathy⁹); serum IGF-1 level 307 ng/ml.

Figure 5

Fluorescein angiogram of the same eye as in Figure 3, before laser coagulation treatment.

Figure 6

Fluorescein angiogram of the same eye as in Figure 4, showing new vessel on the disc.

Figure 7

Dynamics of retinopathy level⁹ (A), serum IGF-1 (B), HbA_1c (C), before and after initiation of improved diabetes control (time 0) in four type 1 diabetic patients (CH, SK, JA, CO).