Patients with type I diabetes have alterations in the GH/IGF system with reduced levels of circulating IGF-I, as well as other disturbances in the components of the IGF system.
Alterations of both local and circulating IGF-I and its binding proteins (IGFBPs) have been associated with metabolic and vascular manifestations of diabetes and also with atherosclerosis. Short-acting insulin analogues have been developed in order to obtain more physiologic insulin profiles than with human regular insulin when injected subcutaneously.
We examined the effects on the IGF system of good glycaemic control, of two diets with different amount of protein and of the short-acting insulin analogue lispro in continuous subcutaneous insulin infusion (CSII) (pump therapy). We also compared the free insulin profiles of the insulin analogues lispro and aspart. As a new tool we used the combination of two different insulin assays that detect human insulin only, or both human insulin and analogues.
This thesis shows that the circulating IGF system exhibits several pronounced aberrations in patients with type I diabetes, even if glycaemic control is normal or near normal. These abnormalities are not, or are only weakly, related to glycaemic control estimated by HbA1c. In contrast, they are related to the presence of residual p-cell function, indicating that portal insulin delivery is required for a normal IGF system. Treatment with insulin analogue lispro, despite giving higher peripheral insulin peaks than human regular insulin, does not alter the levels of IGF-I and IGFBP-I in patients with good glycaemic control and longstanding, Cpeptide negative type 1 diabetes treated with CSII. Furthermore, IGFBP-I levels do not differ after a single s c injection of each of the insulin analogues aspart and lispro. A two-fold increase in protein intake, from 10E% to 20E%, in patients with longstanding type 1 diabetes does not affect the altered IGF system.
The free insulin profiles of insulin analogues aspart and lispro resemble each other, but insulin lispro showed a slightly faster uptake, reached the maximum peak concentration earlier, and showed a more rapid decline than did insulin aspart. These differences are, however, small in comparison with the large differences in the insulin profiles between lispro and human regular insulin. The accumulated evidence suggests that possible differences between these insulin analogues are of little or no clinical importance.
The combination of insulin assays that detect human insulin alone, or both human insulin and analogues provides a new tool for studying insulin pharmacokinetics. Using this technique, it is possible to separately assess the contribution of insulin analogues (lispro and aspart) and human insulin to the free insulin profiles.
Linköping: Linköping University Electronic Press , 2005. , 81 p.
2005-10-28, Aulan, Hälsans Hus, Campus US, Linköpings Universitet, Linköping, 13:00 (Swedish)