| 1. |
- Karimi, Mahssa, et al.
(författare)
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Increased neck soft tissue mass and worsening of obstructive sleep apnoea after growth hormone treatment in men with abdominal obesity : Growth hormone and obstructive sleep apnoea in abdominally obese men
- 2010
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Ingår i: Journal of Clinical Sleep Medicine. - 1550-9389. ; 6:3, s. 256-263
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Tidskriftsartikel (refereegranskat)abstract
- Background Risk factors for obstructive sleep apnea (OSA) are male gender, obesity and abnormalities in neck soft tissue mass. OSA is associated with both growth hormone (GH) excess and severe GH deficiency in adults. Adults with abdominal obesity have markedly suppressed GH secretion. Aim To study the effect of GH treatment on OSA in abdominally obese men with impaired glucose tolerance. Patients and Methods Forty men with abdominal obesity and glucose intolerance were randomized in a prospective, 12-month, double-blind trial to receive either GH or placebo. The treatment groups had similar BMI and waist circumference. Overnight polysomnography and computed tomography to assess muscle and fat distribution in the neck and abdomen were performed at baseline and after 12 months. Results GH treatment increased insulin-like growth-factor-1 from (mean (SD)) 168(17) to 292(28) μg/L, the apnea-hypopnea index from (n/h) 31(20) to 43(25) and oxygen-desaturation index from (n/h) 18(14) to 29(21) (p=0.0001, 0.001, 0.002). Neck transverse diameter, circumference and total cross-sectional area (p=0.007, 0.01, 0.02) increased while abdominal visceral adipose tissue (p=0.007) was reduced. No between-group differences in total sleep time, REM sleep, non-REM sleep and time spent in supine position were found. The Epworth sleepiness scale score was unchanged. Conclusions GH treatment increased the severity of OSA in abdominally obese men. The possible mechanism appears to be reflected by the GH-induced increase of measures of neck volume. The present results, to some extent, argue against that low GH/IGF-I activity is a primary cause of OSA in abdominally obese men.
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| 2. |
- Pannee, Josef, 1979, et al.
(författare)
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The amyloid-beta degradation pattern in plasma A possible tool for clinical trials in Alzheimer's disease
- 2014
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 573, s. 7-12
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid beta (A beta) is the main component of plaques, the central neuropathological hallmark in Alzheimer's disease (AD). A beta is derived from the amyloid precursor protein (APP) by beta- and gamma-secretase-mediated cleavages. A large number of A beta peptides are found in cerebrospinal fluid and these peptides are produced in specific metabolic pathways, which are important for diagnosis, in drug development and to explore disease pathogenesis. To investigate whether a similar pattern could be found also in blood samples, an immunoprecipitation (IP) based method for enrichment of A beta peptides from human plasma was developed. The peptides were analyzed using matrix-assisted-laser-desorption/ionization time-of-flight/time-of-flight mass spectrometry for A beta profiling and selected reaction monitoring (SRM) for MS quantification of A beta 1-38, A beta 1-40 and A beta 1-42 using tripe quadrupole MS. Sixteen N- or C-terminally truncated A beta peptides were reproducibly detected in human plasma, of which 11 were verified by tandem MS. In a pilot study including 9 AD patients and 10 controls, where A beta 1-38, A beta 1-40 and A beta 1-42 were quantified using SRM, no AD-associated change in plasma levels of the peptides were observed. Using MS-based measurement techniques, we show that several A beta peptides can be monitored in a single analysis and the developed methods have the potential to be used as a read out in clinical trials of drugs affecting APP processing or A beta homeostasis.
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| 3. |
- Windahl, Sara H, 1971, et al.
(författare)
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Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice.
- 2011
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- Androgens are important regulators of bone mass but the relative importance of testosterone (T) versus dihydrotestosterone (DHT) for the activation of the androgen receptor (AR) in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2), encoded by separate genes (Srd5a1 and Srd5a2). 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1⁻/⁻ mice. Four-month-old male Srd5a1⁻/⁻ mice had reduced trabecular bone mineral density (-36%, p<0.05) and cortical bone mineral content (-15%, p<0.05) but unchanged serum androgen levels compared with wild type (WT) mice. The cortical bone dimensions were reduced in the male Srd5a1⁻/⁻ mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05) in orchidectomized WT mice but not in orchidectomized Srd5a1⁻/⁻ mice. Male Srd5a1⁻/⁻ mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05). Female Srd5a1⁻/⁻ mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1⁻/⁻ mice, is an indirect effect mediated by elevated circulating androgen levels.
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| 4. |
- Almqvist, Erik G., et al.
(författare)
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Factors influencing insulin sensitivity in patients with mild primary hyperparathyroidism before and after parathyroidectomy
- 2012
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 72:2, s. 92-99
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Primary hyperparathyroidism (PHPT) is associated with cardiovascular disease. The aims of this study were to investigate lipid and glucose metabolism in mild PHPT, and to identify whether insulin sensitivity correlates with circulating levels of adiponectin, SHBG, and osteocalcin before and after parathyroidectomy (PTX). Materials and methods. Forty-five patients with PHPT were examined before and 1 year after PTX. Circulating levels of triglycerides, total cholesterol, HDL-cholesterol, insulin, glucose, adiponectin, SHBG, osteocalcin, and erythropoietin were measured. Results. At baseline, the mean serum levels of total cholesterol, LDL-cholesterol and triglycerides were above the upper reference limit or in the upper normal range, and insulin sensitivity was reduced as assessed using the HOMA index. One year after parathyroidectomy, serum lipids as well as HOMA index and erythropoietin were unchanged while adiponectin had increased (p < 0.05), and SHBG and osteocalcin had decreased (p < 0.05 and p < 0.0001, respectively). HOMA index correlated negatively with circulating levels of adiponectin, SHBG and osteocalcin. In multiple regression analysis SHBG was the most important predictor of insulin sensitivity, both pre- and postoperatively. Conclusion. Untreated mild PHPT is associated with a moderate derangement of lipid and glucose metabolism. As previously shown in population-based cohorts, insulin sensitivity is positively associated with circulating concentrations of adiponectin, SHBG and osteocalcin. One year after PTX, the mean level of adiponectin was increased, but the levels of SHBG and osteocalcin had decreased and the levels of serum lipids and the insulin sensitivity remained unchanged as compared with baseline.
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| 5. |
- Burman, Pia, et al.
(författare)
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Deaths Among Adult Patients With Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality
- 2013
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:4, s. 1466-1475
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Tidskriftsartikel (refereegranskat)abstract
- Context: Patients with hypopituitarism have an increased standardized mortality rate. The basis for Objective: To investigate in detail the cause of death in a large cohort of patients with hypopituitarism Design and Methods: All-cause and cause-specific mortality in 1286 Swedish patients with Main Outcome Measures: Standardized mortality ratios (SMR) were calculated, with stratification for Results: An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence Conclusion: Two important causes of excess mortality were identified: first, adrenal crisis in response
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| 6. |
- Carlzon, Daniel, et al.
(författare)
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Both Low and High Serum Insulin-like Growth Factor-I Levels Associate with Increased Risk of Cardiovascular Events in Elderly Men.
- 2014
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:11
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Most previous prospective studies suggest that low serum insulin-like growth factor-I (IGF-I) associates with increased risk of cardiovascular disease (CVD) events while other studies suggest that high serum IGF-I associates with increased risk of CVD events. We tested the hypothesis that not only low, but also high, serum IGF-I associate with increased risk of CVD events in elderly men. Methods and Results: Serum IGF-I levels were measured in 2901 elderly men (aged 69 to 81 years) included in the prospective population-based MrOS-Sweden cohort. Data for CVD events were obtained from national Swedish registers with no loss of follow-up. During follow-up (median 5.1 yrs) 589 of the participants experienced a CVD event. The association between serum IGF-I and risk of CVD events was nonlinear, and restricted cubic spline Cox regression analysis revealed a U-shaped association between serum IGF-I levels and CVD events (p<0.01 for nonlinearity). Low as well as high serum IGF-I (quintile 1 or 5 vs. quintiles 2-4) significantly associated with increased risk for CVD events (hazard ratio (HR) = 1.25, 95% confidence interval (CI) 1.02-1.54; and HR = 1.35, 95% CI 1.10-1.66, respectively). These associations remained after adjustment for prevalent CVD and multiple risk factors. High serum IGF-I associated with increased risk of coronary heart disease (CHD) events but not with risk of cerebrovascular events. Conclusion: Both low and high serum IGF-I levels are risk markers for CVD events in elderly men. The association between high serum IGF-I and CVD events is mainly driven by CHD events.
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| 7. |
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| 8. |
- Elbornsson, Mariam, et al.
(författare)
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Effects of 3-year growth hormone (GH) replacement therapy on bonemineral density in younger and elderly adults with adult onset GH deficiency.
- 2011
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Little is known of the effects of long-term GH replacement on bone mineral content (BMC) and bone mineral density (BMD) in elderly GH deficient (GHD) adults.Design/Patients/Methods: In this prospective, single-centre, open-label study, the effects of 3-year GH replacement were determined in 45 GHD patients above 65 years of age and in 45 younger control GHD patients with a mean age of 39.5 (SEM 1.1) years. All patients had adult onset disease and both groups were comparable in terms of number of anterior pituitary hormonal deficiencies, gender, body mass index (BMI), and waist:hip ratio.Results: The mean maintenance dose of GH was 0.24 (0.02) mg/day in the elderly patients and 0.33 (0.02) mg/day in the younger GHD patients (p<0.01). The three years of GH replacement induced a marginal effect on total body BMC and BMD whereas femur neck and lumbar (L2-L4) spine BMC and BMD increased in both the elderly and the younger patients. The treatment response in femur neck BMC was less marked in the elderly patients (p<0.05 vs. younger group). However, this difference disappeared after correction for the lower dose of GH in the elderly patients using an analysis of covariance. There were no between-group differences in responsiveness in BMC or BMD at other skeletal locations.Conclusions: This study shows that GH replacement increases lumbar (L2-L4) spine and femur neck BMD and BMC in younger as well as elderly GHD patients. This supports that long-term GH replacement is useful also in elderly GHD patients.
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| 9. |
- Elbornsson, Mariam, et al.
(författare)
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Fifteen years of GH replacement improves body composition and cardiovascular risk factors
- 2013
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 168:5, s. 745-753
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Few studies have determined the effects of more than 5-10 years of GH replacement in adults on body composition and cardiovascular risk factors. Design/patients: In this prospective, single-center, open-label study, the effects of 15 years of GH replacement on body composition and cardiovascular risk factors were determined in 156 hypopituitary adults (93 men) with adult-onset GH deficiency (GHD). Mean age was 50.5 (range 22-74) years at study start. Body composition was measured using dual-energy X-ray absorptiometry. Results: The mean initial GH dose of 0.55 (S. E. M. 0.03) mg/day was gradually lowered to 0.40 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from -1.53 (0.10) at baseline to 0.74 (0.13) at study end (P<0.001 vs baseline). Lean soft tissue (LST) increased to 3% above the baseline level at study end (P<0.001). After a 9% decrease during the first year of treatment (P<0.001 vs baseline), body fat (BF) started to increase and had returned to the baseline level after 15 years. Serum levels of total cholesterol and LDL-cholesterol decreased and serum HDL-cholesterol level increased. Fasting plasma glucose increased from 4.4 (0.1) at baseline to 4.8 (0.1) mmol/l at study end (P<0.001). However, blood HbA1c decreased from 5.0 (0.1) to 4.6 (0.1) % (P<0.001). Conclusions: Fifteen-year GH replacement in GHD adults induced a transient decrease in BF and sustained improvements of LST and serum lipid profile. Fasting plasma glucose increased whereas blood HbA1c was reduced. European Journal of Endocrinology 168 745-753
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| 10. |
- Elbornsson, Mariam, et al.
(författare)
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Fifteen years of GH replacement increases bone mineral density in hypopituitary patients with adult-onset GH deficiency
- 2012
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 166:5, s. 787-795
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Few studies have determined the effects of more than 5-10 years of GH replacement in adults on bone mineral content (BMC) and bone mineral density (BMD). Design/patients: In this prospective, single-centre, open-label study, the effects of 15 years of GH replacement on BMC and BMD, measured using dual-energy X-ray absorptiometry, were determined in 126 hypopituitary adults (72 men) with adult-onset GH deficiency (GHD). Mean age was 49.4 (range 22-74) years at the initiation of the study. Results: The mean initial GH dose of 0.63 (S.E.M. 0.03) mg/day was gradually lowered to 0.41 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from -1.69 (0.11) at baseline to 0.63 (0.16) at the study end (P < 0.001 vs baseline). The 15 years of GH replacement induced a sustained increase in total body BMC (+5%, P < 0.001) and BMD (+2%, P < 0.001). Lumbar (L2-L4) spine BMC increased by 9% (P < 0.001) and BMD by 5% (P < 0.001). In femur neck, a peak increase in BMC and BMD of 7 and 3%, respectively, was observed after 7 years (both P < 0.001). After 15 years, femur neck BMC was 5% above the baseline value (P < 0.01), whereas femur neck BMD had returned to the baseline level. In most variables, men had a more marked response to GH replacement than women. Conclusions: Fifteen-year GH replacement in GHD adults induced a sustained increase in total body and lumbar (L2-L4) spine BMC and BMD. In femur neck, BMC and BMD peaked at 7 years and then decreased towards baseline values.
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