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Treatment with insulin lispro changes the insulin profile but does not affect the plasma concentrations of IGF-I and IGFBP-1 in type 1 diabetes
Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
2001 (English)In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 55, no 1, 107-112 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE IGF-I levels in patients with type 1 diabetes without endogenous insulin production are low. Our aim was to examine whether the plasma insulin profile obtained by treatment with the insulin analogue lispro has a different effect on plasma concentrations of IGF-I and IGFBP-1 than that seen during treatment with conventional human insulin (regular insulin).

DESIGN AND PATIENTS Twelve patients with type 1 diabetes, age 47·8 ± 2·4 years (mean ± SEM), body mass index 26·5 ± 1·0 kg/m2, diabetes duration 30·5 ± 3·2 years participated in this open label randomized cross-over study. IGF-I and IGFBP-1 levels were measured at the end of 6 weeks treatment with each insulin being administered by a continuous subcutaneous insulin infusion. IGF-I was measured fasting while IGFBP-1, free insulin and blood glucose were measured fasting and repeatedly after a morning meal preceded by an insulin bolus dose.

RESULTS Lispro gave a marked insulin peak of 135 ± 20 pmol/l 50 minutes after injection. After an initial rapid rise, human regular insulin reached a plateau of approximately 50 pmol/l. The plasma free insulin area under the curve (AUC) from 0710 h to 0910 h was more than twice as large on lispro as on regular insulin (P = 0·01). Plasma IGF-I concentration was 78·8 ± 10·9 µg/l on lispro and 82·3 ± 10·5 µg/l on human regular insulin (not significant). AUC for IGFBP-1 did not show a significant difference even when divided from 0710 h to 0910 h and from 0930 h to 1430 h. Blood glucose AUC after administration of the bolus was significantly lower during treatment with lispro (P = 0·006) but glycosylated haemoglobin (HbA1c) was 6·4 ± 0·2% on both therapies.

CONCLUSIONS Our results indicate that the effect of lispro on IGF-I and IGFBP-1 in patients with type 1 diabetes does not differ from that of human regular insulin.

Place, publisher, year, edition, pages
2001. Vol. 55, no 1, 107-112 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-24910DOI: 10.1046/j.1365-2265.2001.01327.xLocal ID: 9313OAI: oai:DiVA.org:liu-24910DiVA: diva2:245233
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Insulin and IGF-I in type 1 diabetes
Open this publication in new window or tab >>Insulin and IGF-I in type 1 diabetes
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2005. 81 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 915
Keyword
Type I diabetes, IGF-I, IGF system, insulin, insulin analogues
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-31912 (URN)17745 (Local ID)91-85299-26-X (ISBN)17745 (Archive number)17745 (OAI)
Public defence
2005-10-28, Aulan, Hälsans Hus, Campus US, Linköpings Universitet, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-09-27Bibliographically approved

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Hedman, ChristinaLindström, TorbjörnArnqvist, Hans

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