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- Ekman, Bertil
(författare)
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IGF-I in growth hormone deficiency and in type 1 diabetes
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 2. |
- Lood, Yvonne
(författare)
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Testosterone Use and Abuse : Methodological Aspects in Forensic Toxicology and Clinical Diagnostics
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abuse of anabolic androgenic steroids (AAS) is widespread in society and is today a major public health problem, associated with mental and somatic adverse effects and risk behavior, such as use of other illicit drugs and criminality. Testosterone, the most important endogenous male androgen, is therapeutically used in replacement therapy but is also extensively used as a doping agent. Traditionally, testosterone abuse is detected in urine in forensic cases and in serum in clinical diagnosis and monitoring, and free bioavailable serum testosterone is calculated by formulas. Salivary testosterone is however an attractive biomarker, as testosterone in saliva is supposed to reflect free testosterone in serum. The aim of this thesis was to investigate the abuse of AAS from a forensic perspective, particularly focusing on testosterone and methodological problems and potential alternative matrices for measurements of testosterone in forensic and clinical assessments. In the first study the toxicological findings in individuals suspected of doping offences, registered in the Swedish national forensic toxicology database were investigated (paper I). In paper II, testosterone levels in serum, saliva, and urine in clinical patients during replacement therapy with testosterone undecanoate (Nebido®) were studied. Further, the sensitivity of the current procedure for detection of testosterone abuse was investigated by method comparison using isotope ratio measurement (paper III) and a quantitative LC-MS/MS method for testosterone in serum and saliva was developed and presented (paper IV). It was found that testosterone was most frequently detected in the forensic cases and co-abuse of narcotics was common among AAS abusers. Methodological problems in detection of testosterone abuse using the present procedures was identified, indicating a need for new analytical strategies. A sensitive and highly specific LC-MS/MS method was developed for determination of testosterone in serum and saliva, which was shown suitable for analysis of forensic and clinical samples. Salivary testosterone was shown to correlate well with free serum testosterone in both male and female, and a sensitive marker in testosterone therapy, especially in females. In conclusion, it was found that saliva might have a potential as an alternative matrix for detection of illicit administration of testosterone and for diagnosis and monitoring of androgenic status.
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