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Improved muscle function in GH substituted adults is related to increase in circulating IGF-I
Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation 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.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

We studied the effects of individualized growth hormone substitution, aiming at normal IGF-I levels, on biomechanical output and EMG of isokinetic muscle strength and endurance performance in 18 hypopituitary adults compared with matched controls. The muscle function tests consisted of isokinetic contractions of the dght knee extensors, and torque and EMG were recorded. Plasma levels of IGF-I were normalized, and peak torque at 90° s-1, and peak torque endurance level increased after dose titration and 6 months constant GH-dose. The change in IGF-I correlated positively with the changes in biomechanical output and EMG variables and a negative correlation existed with the perception of fatigue. Despite improvement during GH-substitution the patients still had about 10-20 % less muscle strength and endurance compared with the controls at the study end. In summary we found that individualized GH substitution improves muscle function and that the net increase in IGF-I levels indicates generally increases in biomechanical output and EMG variables and a lower perception of fatigue.

National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-81632OAI: diva2:555295
Available from: 2012-09-19 Created: 2012-09-19 Last updated: 2012-09-19Bibliographically approved
In thesis
1. IGF-I in growth hormone deficiency and in type 1 diabetes
Open this publication in new window or tab >>IGF-I in growth hormone deficiency and in type 1 diabetes
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Both GH-deficiency and type 1 diabetes are associated with low IGF-I levels. The aim with our studies was to develop a dose titration model to obtain physiological IGF-I levels in growth hormone deficiency and to evaluate the relationship between glycaemic control and IGF-I in diabetes. First we established reference values for insulin like growth factor-I (IGF-I) and insulin like growth factor bindingprotein-1 (IGFBP-1) from 101 women and 101 men randomly selected from the population registry. No gender differences in IGF-I levels were fmmd. IGF-1 decreases with advancing age in both sexes, whereas IGFBP-1 increases with age.

Titrating the GH dose according to population based reference values of IGF-I might be a way to obtain a fairly physiological substitution dose of GH. We hypothesised that a safe and probably effective maintenance dose of GH should increase IGF-I to the mean or slightly below the mean according to age adjusted reference levels. Eighteen adult hypopituitary patients with severe GH deficiency were titrated in steps, according to age adjusted IGF-I levels, to an individual dose of recombinant GH. For comparison 17 untreated healthy control subjects were evaluated. Similar IGF-1 levels armmd the mean for corresponding age were obtained in both sexes, but the maintenance median GH dose was more than twice in the women compared to men. The :individual dose differed markedly and elderly patients needed lower GH doses due to unchanged GH-sensitivity. Six months on the maintenance GH dose induced changes in blood-glucose, lipids, and insulin sensitivity index, indicating increased insulin resistance, which compared with the controls, were a normalisation. No major changes were seen in the variables of the renin-angiotensin-system. A significant increase in atrial natriuretic peptide seems also to be a normalisation if compared with the controls. The patients had less muscle strength and endmance at baseline compared with the controls and increased the muscle strength and endmance about 10 % after GH-substitution, an effect associated with the increase in IGF-I.

Paradoxically circulating IGF-I is decreased in type 1 diabetes despite increased GH levels. We studied 134 adult patients with type I diabetes (aged 20-60 years), without endogenous insulin secretion, and found that circulating IGF-I were decreased to about 70 % of the values in the reference population. No con·elation between glycaemic control and IGF-I levels was found.

To conclude the GH dose obtained when normalising circulating IGF-I according to population-based IGF-I levels, depends on GH-sensitivity (gender) and the IGF-1 level aimed for (age). In comparison with matched controls several OR-dependent variables are improved. In type 1 diabetes, our results suggests that the low IGF-I levels are independent of glycaemic control, and can not be corrected with subcutaneous insulin substitution.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2002. 66 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 757
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-25640 (URN)10015 (Local ID)91-7373-485-3 (ISBN)10015 (Archive number)10015 (OAI)
Public defence
2002-12-05, Administrationsbyggnadens aula, Hälsouniversitetet, Linköping, 13:00 (Swedish)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-19Bibliographically approved

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