| 1. |
- Cunningham, Janet L., et al.
(author)
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Connective tissue growth factor expression in endocrine tumors is associated with high stromal expression of alpha-smooth muscle actin
- 2010
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In: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 163:4, s. 691-697
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Journal article (peer-reviewed)abstract
- OBJECTIVE Complications due to fibrosis development are common in patients with well-differentiated endocrine carcinomas in the small intestine (ileal carcinoids). Connective tissue growth factor (CTGF) expression in ileal carcinoids may be related to this fibrosis development. This study aimed to examine CTGF expression in relation to local myofibroblast differentiation in a large series of ileal carcinoids and in different types of endocrine tumors. METHODS Immunoreactivity (IR) for CTGF and α-smooth muscle actin (α-SMA), a marker for myofibroblasts, was compared in serial tumor tissue sections from 42 patients with ileal carcinoids and from 80 patients with other endocrine tumors. Western blot was performed on an additional 21 patients with ileal carcinoids. RESULTS CTGF IR was present in >50% of tumor cells in all 42 ileal carcinoids and in 2 out of 14 endocrine pancreatic tumors, 4 out of 6 rectal carcinoids, and 1 out of 5 lung carcinoids. Tumors with abundant CTGF expression also displayed α-SMA IR in stromal fibroblast-like cells, whereas other endocrine tumors displayed less or no CTGF and α-SMA IR. Protein bands corresponding to full-length CTGF (36-42 kDa) were detected in protein lysates from ileal carcinoids. CONCLUSION CTGF is uniquely prevalent in ileal carcinoids when compared with most other endocrine tumor types. Immunoreactive cells are adjacent areas with increased fibrovascular stroma that express α-SMA. This supports a potential role for CTGF in myofibroblast-mediated fibrosis associated with ileal carcinoids, and indicates that CTGF should be investigated as a target for future therapy.
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| 2. |
- Gustafsson, Stefan, et al.
(author)
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Adiponectin and cardiac geometry and function in elderly : results from two community-based cohort studies
- 2010
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In: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 162:3, s. 543-550
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Several smaller studies have indicated that adiponectin might be associated with left ventricular (LV) mass and function, but community-based studies with adequate sample size and adjustment for potential confounders are lacking. Our objective was to investigate such associations in two large community-based studies of elderly. DESIGN: Cross-sectional. METHODS: We evaluated cross-sectional relations between serum adiponectin and echocardiographic measures of cardiac geometry and function (LV mass index, LV relative wall thickness, LV end-diastolic diameter, left atrial diameter, ejection fraction, LV isovolumic relaxation time, and E/A ratio) in 954 70-year-old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), and in 427 71-year-old men from the Uppsala Longitudinal Study of Adult Men (ULSAM). RESULTS: In models adjusted for age, sex, body mass index, systolic blood pressure, antihypertensive treatment, antidiabetic treatment, lipid-lowering medication, fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, creatinine, and smoking, adiponectin was inversely associated with ejection fraction in men (beta, -1.62; 95% confidence interval (CI), -2.50, -0.75 in PIVUS; beta, -1.35; 95% CI, -2.41, -0.29 in ULSAM), but not in women. After additional adjustment for N-terminal pro-brain natriuretic peptide (NT-proBNP), the association between adiponectin and ejection fraction was attenuated (beta, -0.98; 95% CI, -1.86, -0.10 in PIVUS; beta, -0.75; 95% CI, -1.84, 0.35 in ULSAM). CONCLUSIONS: Serum adiponectin concentrations were associated with ejection fraction in men, and these associations were partially attenuated by NT-proBNP. Our results imply that adiponectin may be associated with systolic function through pathways that involve natriuretic peptides.
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| 3. |
- Rehman, Javaid-ur, et al.
(author)
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Sleeping during the day : effects on the 24-h patterns of IGF-binding protein 1, insulin, glucose, cortisol, and growth hormone.
- 2010
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In: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 163:3, s. 383-90
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Journal article (peer-reviewed)abstract
- BACKGROUND: Disturbed sleep is a major risk factor for metabolic disturbances, including type 2 diabetes, but the involved mechanisms are still poorly understood. We investigated how an acute shift of sleep to the daytime affected IGF-binding protein 1 (IGFBP1), which is a risk factor for diabetes. METHODS: Seven healthy men (age, 22-32 years) participated in a night sleep condition (sleep 2300-0700 h) and a day sleep condition (0700-1500 h) with hourly blood samples taken for 25 h (starting at 1900 h) and isocaloric meals every 4th hour awake. The blood samples were analyzed for IGFBP1, insulin, GH, glucose, and cortisol. RESULT: The acute shift of sleep and meal timing (to 8 h) shifted the 24-h patterns of IGFBP1, glucose, insulin, and GH to a similar degree. However, the day sleep condition also resulted in elevated levels of IGFBP1 (area under curve (AUC)+22%, P<0.05), and reduced glucose levels (AUC-7%, P<0.05) compared with nocturnal sleep. Sleeping during the day resulted in elevated cortisol levels during early sleep and reduced levels in late sleep, but also in increased levels the subsequent evening (P's<0.05). CONCLUSION: Sleep-fasting seems to be the primary cause for the elevation of IGFBP1, irrespective of sleep timing. However, sleeping during the day resulted in higher levels of IGFBP1 than nocturnal sleep, suggesting altered metabolism among healthy individuals, which may have implications for other groups with altered sleep/eating habits such as shift workers. Moreover, sleep and meal times should be accounted for while interpreting IGFBP1 samples.
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| 4. |
- Vandenput, Liesbeth, et al.
(author)
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Serum estradiol is associated with lean mass in elderly Swedish men
- 2010
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In: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 162:4, s. 737-745
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Association studies in men have shown that androgens are inversely related to fat measures, while the relation between sex steroids and lean mass remains unclear. We, therefore, investigated the associations between serum sex steroid levels and body composition in elderly men with a main focus on lean mass measures. DESIGN AND METHODS: A cross-sectional survey of a population-based cohort of 3014 elderly men, aged 69-80 years (Osteoporotic Fractures in Men study, Sweden). Serum levels of testosterone and estradiol (E(2)) were measured by mass spectrometry, sex hormone-binding globulin (SHBG) levels were measured by IRMA, and measures of body composition were obtained by dual-energy X-ray absorptiometry. RESULTS: Total as well as free serum testosterone associated independently inversely (P<0.001), while total as well as free serum E(2) associated independently directly (P<0.001) with total body fat mass and trunk fat mass. Serum SHBG associated independently inversely with central fat distribution. Serum E(2) and free E(2) but not serum testosterone or free testosterone levels associated positively with lean mass (P<0.01). Elderly men within the lowest quartile of free E(2) had 0.5 kg less lean mass in the legs than subjects within the highest quartile, while the subjects in the different quartiles of free testosterone did not differ in lean mass. CONCLUSIONS: Serum E(2), but not serum testosterone, is directly associated with lean mass in this large study of elderly Swedish men. In addition, serum SHBG is associated with central fat distribution and we confirmed that serum testosterone is inversely associated with fat mass.
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| 5. |
- Åstrand, Olov, et al.
(author)
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Weight gain by hyperalimentation elevates C-reactive protein levels but does not affect circulating levels of adiponectin or resistin in healthy subjects
- 2010
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In: European Journal of Endocrinology. - Bristol : BioScientifica. - 0804-4643 .- 1479-683X. ; 163:6, s. 879-885
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Journal article (peer-reviewed)abstract
- Objective: Increase of resistin and/or reduction of adiponectin have beenimplicated in the development of insulin resistance followingweight gain. We aimed to study this prospectively in humans.Design: Prospective and interventional with parallel control group.Methods: Twelve healthy men and six healthy women (age 26±6.6years) and an age-matched control group were recruited. Subjectsin the intervention group aimed for a bodyweight increase of5–15% by doubling the baseline caloric intake by eatingat least two fast food-based meals a day in combination withadoption of a sedentary lifestyle for 4 weeks.Results: Bodyweight increased from 67.6±9.1 to 74.0±11kg, P<0.001, by the intervention. Insulin levels increased(before: 27.4±12 pmol/l, after: 53.0±22 pmol/l,P=0.004), while plasma levels of adiponectin (before: 5038±3736ng/ml, after: 6739±7949 ng/ml, P=0.18) and resistin (before:21.8±19 ng/ml, after: 14.4±6.8 ng/ml, P=0.074)remained unchanged by the weight gain and were similar as incontrols. On the other hand, leptin levels increased about threefoldfollowing the intervention (before: 5.7±7.4, after: 16±20ng/ml, P=0.008), and also the inflammatory marker C-reactiveprotein (CRP) increased from 0.34±0.44 to 0.71±0.87mg/l, P=0.03, when two outliers >10 mg/l were disregarded.Conclusions: Hyperalimentation reduces insulin sensitivity when weight gainof 9% was combined with reduction of exercise. However, thelevels of resistin and adiponectin were unaffected by the intervention,while CRP levels increased within this short time period suggestingthat low-grade inflammation can occur early in the process ofdeveloping a metabolic syndrome.
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| 9. |
- Götherström, Galina, 1962, et al.
(author)
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Muscle strength in elderly adults with GH deficiency after 10 years of GH replacement.
- 2010
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In: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 163:2, s. 207-15
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Journal article (peer-reviewed)abstract
- CONTEXT: Only few studies have investigated the effects of GH replacement on muscle strength in elderly patients with GH deficiency (GHD). OBJECTIVE, DESIGN, AND PATIENTS: In this prospective open-labeled study, the effects of 10 years of GH replacement on muscle strength and neuromuscular function were followed in 24 elderly GHD adults (mean age of 65.2 years; range 61-74 years). Muscle strength was compared with reference values obtained from the background population. RESULTS: The mean initial GH dose of 0.72 mg/day was lowered to 0.37 mg/day. The mean IGF1 SDS increased from -1.10 at baseline to 1.17 at study end. GH replacement induced a sustained increase in lean body mass and a transient increase in isometric knee flexor strength. Isometric knee extensor strength was reduced after 10 years. However, after correction for age and gender, using observed/predicted value ratios, there was sustained and even progressive increase in most variables reflecting muscle strength. Measurements of neuromuscular function showed unchanged voluntary motor unit activation after 10 years. CONCLUSIONS: Ten years of GH replacement therapy in elderly GHD adults resulted in a transient increase in isometric knee flexor strength, and provided protection from most of the normal age-related decline in muscle performance and neuromuscular function.
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| 10. |
- Höybye, Charlotte, et al.
(author)
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Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease.
- 2010
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In: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 162:4, s. 677-84
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Patients in remission from Cushing's disease (CD) have many clinical features that are difficult to distinguish from those of concomitant GH deficiency (GHD). In this study, we evaluated the features of GHD in a large cohort of controlled CD patients, and assessed the effect of GH treatment. DESIGN AND METHODS: Data were obtained from KIMS, the Pfizer International Metabolic Database. A retrospective cross-sectional comparison of background characteristics in unmatched cohorts of patients with CD (n=684, 74% women) and nonfunctioning pituitary adenoma (NFPA; n=2990, 39% women) was conducted. In addition, a longitudinal evaluation of 3 years of GH replacement in a subset of patients with controlled CD (n=322) and NFPA (n=748) matched for age and gender was performed. RESULTS: The cross-sectional study showed a significant delay in GHD diagnosis in the CD group, who had a higher prevalence of hypertension, fractures, and diabetes mellitus. In the longitudinal, matched study, the CD group had a better metabolic profile but a poorer quality of life (QoL) at baseline, which was assessed with the disease-specific questionnaire QoL-assessment of GHD in adults. After 3 years of GH treatment (mean dose at 3 years 0.39 mg/day in CD and 0.37 mg/day in NFPA), total and low-density lipoprotein cholesterol decreased, while glucose and HbAlc increased. Improvement in QoL was observed, which was greater in the CD group (-6 CD group versus -5 NFPA group, P<0.01). CONCLUSION: In untreated GHD, co-morbidities, including impairment of QoL, were more prevalent in controlled CD. Overall, both the groups responded similarly to GH replacement, suggesting that patients with GHD due to CD benefit from GH to the same extent as those with GHD due to NFPA.
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