ORCADIAN VARIATION OF GH‐INDEPENDENT IGF‐BINDING PROTEIN IN DIABETES MELLITUS AND ITS RELATIONSHIP TO INSULIN. A NEW ROLE FOR INSULIN?

Abstract

SUMMARY: Evidence is accumulating that a non‐GH dependent insulin‐like growth factor‐binding protein (IGF‐BP) is not only a carrier protein but also has an active role in the growth process. We have measured levels of this IGF‐BP, using a specific RIA, over 12 or 24‐h periods in 11 adolescents with diabetes mellitus and five normal adults. In each of the normals the IGF‐BP was undetectable for most of the day but with a broad nocturnal peak observed, with levels up to 50 μU/l. The levels of IGF‐BP were unrelated to the secretory pattern for GH but correlated inversely with the concentration of circulating insulin. In the diabetics a very similar pattern was observed, but with detectable levels throughout the day and much higher peak levels seen at night. Peak levels were up to 120 μg/1 if a long‐acting insulin preparation was administered in the evening but were 400–500 μg/1 if the long‐acting preparation was administered in the morning. The IGF‐BP was strongly correlated with plasma glucose in this latter group. In a further group of diabetics overnight profiles were obtained on two separate nights, a normal night and a night with euglycaemia maintained with a glucose clamp technique. Euglycaemia failed to affect peak levels of the binding protein, although the shape of the nocturnal peak was altered consistent with the altered pattern of circulating free insulin. In this group a strong inverse correlation was obtained between the IGF‐BP and free insulin levels.