The relationship between the circulating IGF system and the presence of retinopathy in Type 1 diabetic patients.
BACKGROUND
Patients with proliferative diabetic retinopathy (PDR) have increased vitreous levels of insulin-like growth factor (IGF)-I, IGF-II and IGF binding proteins (IGFBPs). This accumulation is probably caused by increased leakiness of the blood-retina barrier and influx of circulating IGFs and IGFBPs. To date, interest has focused on the role of circulating total IGF-I in the development of PDR, and there are only sparse data on circulating levels of free IGF-I and IGFBPs.


METHODS
We compared fasting serum samples from matched groups of Type 1 diabetic patients with no retinopathy (n = 29), non-PDR (n = 13) and PDR (n = 16). We also included matched controls (n = 26). Serum was analysed for free and total IGF-I and -II, free plus dissociable IGF-I, IGFBP-1, -2 and -3, IGFBP-1-bound IGF-I as well as IGFBP-3 proteolysis.


RESULTS
When compared with controls, diabetic patients (n = 58) showed reduced (P < 0.0005) levels of free and total IGFs, free plus dissociable IGF-I and IGFBP-3, whereas levels of IGFBP-1, IGFBP-1-bound IGF-I and IGFBP-2 were elevated. IGFBP-3 proteolysis remained unaltered. When comparing diabetic patients with different degrees of retinopathy, IGFBP-2 and IGFBP-1-bound IGF-I were the only parameters that differed significantly. Patients with retinopathy (non-PDR as well as PDR) had elevated IGFBP-2 (P < 0.03) and reduced IGFBP-1-bound IGF-I (P < 0.03), when compared with patients without retinopathy. Noteworthy, both parameters correlated (0.11 < r2 < 0.14, P < 0.02) with the severity of retinopathy.


CONCLUSIONS
Our study gives no evidence of a direct role of circulating free IGF-I in the development of PDR, whereas IGFBP-2 and IGFBP-1-bound IGF-I showed a relationship with the degree of retinopathy. However, further investigations are needed in order to clarify the basis and clinical relevance of this finding.
Frystyk
J
J
Medical Research Laboratories, Institute of Experimental Clinical Research, Aarhus University Hospital, Aarhus, Denmark. jan@frystyk.dk
Bek
T
T
Flyvbjerg
A
A
Skjaerbaek
C
C
Ørskov
H
H
D000328:Adult; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000097:blood* / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis* / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D008875:Middle Aged
D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I