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  • 1.
    Alvehus, Malin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Simonyte, Kotryna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Andersson, Therése
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Söderström, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Burén, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rask, Eva
    Örebro Univ Hosp, Dept Med, Örebro, Sweden.
    Mattsson, Cecilia
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Adipose tissue IL-8 is increased in normal weight women after menopause and reduced after gastric bypass surgery in obese women2012Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, nr 5, s. 684-690Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective:  The menopausal transition is characterized by increased body fat accumulation, including redistribution from peripheral to central fat depots. This distribution is associated with an increased risk of type 2 diabetes and cardiovascular disease which are linked to low-grade inflammation. We determined whether postmenopausal women have higher levels of inflammatory markers, compared to premenopausal women. We also wanted to determine if these markers are reduced by stable weight loss in obese women. Design and methods:  Anthropometric data, blood samples, and subcutaneous adipose tissue biopsies were collected from normal weight premenopausal and postmenopausal women and obese women before and 2 years after gastric bypass surgery. Serum protein levels and adipose tissue gene expression of inflammatory markers were investigated. Results:  IL-8 expression in adipose tissue and circulating levels were higher in postmenopausal versus premenopausal women. IL-8 expression was associated with waist circumference, independent of menopausal status. IL-6 expression and serum levels of monocyte chemoattractant protein (MCP)-1 were higher in postmenopausal versus premenopausal women. Two years after gastric bypass surgery, adipose expression of IL-8, tumor necrosis factor-α, and MCP-1 decreased significantly. Serum insulin levels were associated with inflammation-related gene expression before gastric bypass surgery, but these associations disappeared after surgery. Conclusion:  Postmenopausal women have an increased inflammatory response in the subcutaneous fat and circulation. Inflammatory markers in adipose tissue decreased significantly after surgery-induced weight loss. This effect may be beneficial for metabolic control and reduced cardiovascular risk after weight loss. © 2011 Blackwell Publishing Ltd.

  • 2. Atiomo, William
    et al.
    Shafiee, Mohamad Nasir
    Chapman, Caroline
    Metzler, Veronika M.
    Abouzeid, Jad
    Latif, Ayşe
    Chadwick, Amy
    Kitson, Sarah
    Sivalingam, Vanitha N.
    Stratford, Ian J.
    Rutland, Catrin S.
    Persson, Jenny L.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Clinical Research Center, Lund University, Malmö, Sweden.
    Ødum, Niels
    Fuentes-Utrilla, Pablo
    Jeyapalan, Jennie N.
    Heery, David M.
    Crosbie, Emma J.
    Mongan, Nigel P.
    Expression of NAD(P)H quinone dehydrogenase 1 (NQO1) is increased in the endometrium of women with endometrial cancer and women with polycystic ovary syndrome2017Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 87, nr 5, s. 557-565Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Women with a prior history of polycystic ovary syndrome (PCOS) have an increased risk of endometrial cancer (EC). Aim: To investigate whether the endometrium of women with PCOS possesses gene expression changes similar to those found in EC. Design and Methods: Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross-sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC. Expression of a subset of differentially expressed genes identified by RNA sequencing, including NAD(P)H quinone dehydrogenase 1 (NQO1), was validated by quantitative reverse transcriptase PCR validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1 was validated by immunohistochemistry in EC samples from a separate cohort (n = 91) comprised of consecutive patients who underwent hysterectomy at St Mary's Hospital, Manchester, between 2011 and 2013. A further 6 postmenopausal women with histologically normal endometrium who underwent hysterectomy for genital prolapse were also included. Informed consent and local ethics approval were obtained for the study. Results: We show for the first that NQO1 expression is significantly increased in the endometrium of women with PCOS and EC. Immunohistochemistry confirms significantly increased NQO1 protein expression in EC relative to nonmalignant endometrial tissue (P < .0001). Conclusions: The results obtained here support a previously unrecognized molecular link between PCOS and EC involving NQO1.

  • 3.
    Brorsson, Camilla
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Dahlqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nilsson, Leif
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Naredi, Silvana
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Saliva stimulation with glycerine and citric acid does not affect salivary cortisol levels2014Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 81, nr 2, s. 244-248Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    In critically ill patients with hypotension, who respond poorly to fluids and vasoactive drugs, cortisol insufficiency may be suspected. In serum over 90% of cortisol is protein-bound, thus routine measures of total serum cortisol may yield 'false lows' due to hypoproteinaemia. Thus, the occurrence of cortisol insufficiency could be overestimated in critically ill patients. Salivary cortisol can be used as a surrogate for free serum cortisol, but in critically ill patients saliva production is decreased, and insufficient volume of saliva for analysis is a common problem. The aim of this study was to investigate if a cotton-tipped applicator with glycerine and citric acid could be used for saliva stimulation without affecting salivary cortisol levels.

    DESIGN:

    Prospective, observational study.

    PARTICIPANTS:

    Thirty-six volunteers (six males, 30 females), age 49 ± 9 years, without known oral mucus membrane rupture in the mouth.

    MEASUREMENTS:

    Forty-two pairs of saliva samples (22 paired morning samples, 20 paired evening samples) were obtained before and after saliva stimulation with glycerine and citric acid. Salivary cortisol was analysed using Spectria Cortisol RIA (Orion Diagnostica, Finland).

    RESULTS:

    The paired samples correlated significantly (P < 0·0001) and there was no significant difference between un-stimulated and stimulated salivary cortisol levels.

    CONCLUSIONS:

    Saliva stimulation with a cotton-tipped applicator containing glycerine and citric acid did not significantly influence salivary cortisol levels in healthy volunteers. This indicates that salivary cortisol measurement after saliva stimulation may be a useful complement when evaluating cortisol status in critically ill patients.

  • 4. Decker, Ralph
    et al.
    Albertsson-Wikland, Kerstin
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Halldin, Maria
    Dahlgren, Jovanna
    Decreased GH dose after the catch-up growth period maintains metabolic outcome in short prepubertal children with and without classic GH deficiency2012Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, nr 3, s. 407-415Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Few studies have evaluated metabolic outcomes following growth hormone (GH) treatment in short prepubertal children during different periods of growth. Previously, we found that individualized GH dosing in the catch-up period reduced the variation in fasting insulin levels by 34% compared with those receiving a standard GH dose. We hypothesized that the GH dose required to maintain beneficial metabolic effects is lower during the prepubertal growth phase after an earlier catch-up growth period.

    DESIGN: Short prepubertal children with isolated GH deficiency or idiopathic short stature were randomized to individualized GH treatment (range, 17-100 μg/kg/day) or a standard dose in a preceding 2-year study. After achieving near mid-parental height(SDS) (,) children receiving an individualized dose were randomized to either a 50% reduced individualized dose (RID, n=28) or an unchanged individualized dose (UID, n=37) for 2 years. The dose remained unchanged in 33 children initially randomized to receive a standard dose (FIX, 43 μg/kg/day).We evaluated whether the variations in metabolic parameters measured during maintenance growth diminished in RID compared with UID or FIX.

    RESULTS: We observed less variation in fasting insulin levels (-50%), insulin sensitivity as assessed by homeostasis model assessment (-55.1%), lean soft tissue (-27.8%) and bone mineral content (-31.3%) in RID compared with UID (all p<0.05), but no differences compared with FIX.

    CONCLUSIONS: Continued individualized GH treatment after the catch-up growth period is safe and reduces hyperinsulinism. Individualized GH dose can be reduced once the desired height(SDS) is achieved to avoid overtreatment in terms of metabolic outcome.

  • 5.
    Decker, Ralph
    et al.
    Department of Pediatrics, Gothenburg Pediatric Growth Research Center (GP-GRC), University of Gothenburg, Institute of Clinical Sciences, The Queen Silvia Children’s Hospital, Gothenburg.
    Albertsson-Wikland, Kerstin
    Department of Pediatrics, Gothenburg Pediatric Growth Research Center (GP-GRC), University of Gothenburg, Institute of Clinical Sciences, The Queen Silvia Children’s Hospital, Gothenburg.
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Nierop, Andreas F M
    Muvara bv, Multivariate Analysis of Research Data, Leiderdorp, Netherlands.
    Gustafsson, Jan
    Department of Women’s and Children’s Health, Uppsala University, Uppsala.
    Bosaeus, Ingvar
    Department of Clinical Nutrition, Research Centre for Endocrinology and Metabolism, Sahlgrenska, University Hospital, Gothenburg, Sweden.
    Fors, Hans
    Department of Pediatrics, Gothenburg Pediatric Growth Research Center (GP-GRC), University of Gothenburg, Institute of Clinical Sciences, The Queen Silvia Children’s Hospital, Gothenburg.
    Hochberg, Ze'ev
    Division of Pediatric Endocrinology, Rambam Medical Centre, Haifa, Israel.
    Dahlgren, Jovanna
    Department of Pediatrics, Gothenburg Pediatric Growth Research Center (GP-GRC), University of Gothenburg, Institute of Clinical Sciences, The Queen Silvia Children’s Hospital, Gothenburg.
    Metabolic outcome of GH treatment in prepubertal short children with and without classical GH deficiency2010Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 73, nr 3, s. 346-354Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context  Few studies have evaluated the metabolic outcomes of growth hormone (GH) treatment in idiopathic short stature (ISS). Moreover, children with ISS appear to need higher GH doses than children with GH deficiency (GHD) to achieve the same amount of growth and may therefore be at increased risk of adverse events during treatment. The individualized approach using prediction models for estimation of GH responsiveness, on the other hand, has the advantage of narrowing the range of growth response, avoiding too low or high GH doses.

    Design  Short prepubertal children with either isolated GHD (39) or ISS (89) participated in a 2-year randomized trial of either individualized GH treatment with six different GH doses (range, 17–100 μg/kg/day) or a standard dose (43 μg/kg/day).

    Objective  To evaluate if individualized GH treatment reduced the variance of the metabolic measures as shown for growth response and to compare changes in metabolic variables in children with ISS and GHD.

    Hypothesis  Individualized GH dose reduces the range of metabolic outcomes, and metabolic outcomes are similar in children with ISS and GHD.

    Results  We observed a narrower variation for fasting insulin (−34·2%) and for homoeostasis model assessment (HOMA) (−38·9%) after 2 years of individualized GH treatment in comparison with standard GH dose treatment. Similar metabolic changes were seen in ISS and GHD. Delta (Δ) height SDS correlated with Δinsulin-like growth factor I (IGF-I), Δleptin and Δbody composition. Principal component analysis identified an anabolic and a lipolytic component. Anabolic variables [Δlean body mass (LBM) SDS and ΔIGF-I SDS] clustered together and correlated strongly with Δheight SDS and GH dose, whereas lipolytic variables [Δfat mass (FM) SDS and Δleptin] were clustered separately from anabolic variables. Regression analysis showed GH dose dependency in ISS, and to a lesser degree in GHD, for ΔLBM SDS and Δheight SDS, but not for changes in FM.

    Conclusions  Individualized GH dosing during catch-up growth reduces the variance in insulin and HOMA and results in equal metabolic responses irrespective of the diagnosis of GHD or ISS.

  • 6. Elgzyri, Targ
    et al.
    Castenfors, Jan
    Hägg, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Backman, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Thorén, Marja
    Bramnert, Margareta
    The effects of GH replacement therapy on cardiac morphology and function, exercise capacity and serum lipids in elderly patients with GH deficiency2004Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 61, nr 1, s. 113-122Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives:  To assess effects of GH replacement therapy on cardiac structure and function, exercise capacity as well as serum lipids in elderly patients with GH deficiency (GHD).

    Patients and methods:  Thirty-one patients (six females, 25 males), aged 60–79 years (mean 68 years) with GHD on stable cortisone and thyroxine substitution were studied. All men with gonadotropin deficiency had testosterone and one woman had oestrogen replacement. They were randomized in a double-blind manner to GH or placebo treatment for 6 months, followed by another 12 months GH (Humatrope, Eli Lilly & Co, Uppsala, Sweden). GH dose was 0·017 mg/kg/week for 1 month and then 0·033 mg/kg/week divided into daily subcutaneous injections at bedtime. Echocardiography, exercise capacity tests and serum lipid measurements were performed at 0, 6, 12 and 18 months.

    Results:  During the 6-month placebo-controlled period there were no significant changes in the placebo group, but in the GH-treated group there was a significant increase in IGF-I to normal levels for age, with median IGF-I from 6·9 to 18·5 nmol/l, increase in resting heart rate and maximal working capacity. During the open GH study, IGF-I increased from 8·7 to 19·2 nmol/l at 6 months and 18·8 nmol/l at 12 months (P ≤ 0·001). At 6 months, in the open GH study group, a minor decrease in aortic outflow tract integral (VTI) from 21·8 to 20·7 cm (P = 0·031) and an increase in heart rate at rest from 63 to 67 bpm (P = 0·017), heart rate at maximum exercise from 138 to 144 bpm (P = 0·005) and maximum load at exercise from 142 to 151 Watts (P = 0·014) were seen. These changes were temporary and returned at 12 months with no significant difference from baseline values. Left ventricular dimensions and blood pressure showed no significant changes. At 6 months, in the open GH study group, there was a significant decrease in serum low-density lipoprotein (LDL) cholesterol from 3·7 to 3·4 mmol/l (P = 0·006), a decrease in LDL/HDL ratio from 3·4 to 3·1 (P = 0·036) and a decrease in serum total cholesterol from 5·6 to 5·3 mmol/l (P = 0·036). At 12 months, serum lipids showed same changes with a significant decrease in serum LDL cholesterol (P = 0·0008), in LDL/HDL ratio (P = 0·0005) and in serum total cholesterol (P = 0·049). Serum HDL cholesterol showed no significant change at 6 months, at 12 months a significant increase was seen from 1·2 to 1·4 mmol/l (P = 0·007). There were no significant changes in serum triglycerides.

    Conclusions:  GH substitution to elderly patients with GHD caused only a transient increase in heart rate. At the end of the 12 months there were no significant changes on cardiac noninvasive structural and functional parameters. Maximal working capacity transiently improved. Thus, the therapy was safe without negative effects on cardiac structural and functional noninvasive parameters. Lipid profiles improved with reduction of serum LDL cholesterol accompanied by significant improvement of LDL/HDL ratio and serum HDL cholesterol after 12 months treatment.

  • 7. El-Mansoury, Mostafa
    et al.
    Berntorp, Kerstin
    Bryman, Inger
    Hanson, Charles
    Innala, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Karlsson, Anders
    Landin-Wilhelmsen, Kerstin
    Elevated liver enzymes in Turner syndrome during a 5-year follow-up study2008Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 68, nr 3, s. 485-490Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives  To study the prevalence and incidence of elevated liver enzymes and their relationship with body weight, metabolic factors and other diseases in Turner syndrome (TS).

    Design  Five-year follow-up.

    Patients  Women with TS (n = 218, mean age 33 ± 13, range 16–71 years) from outpatient clinics at university hospitals in Sweden.

    Measurements  Fasting blood samples for aspartate (AST) and alanine aminotransferase (ALT), bilirubin, alkaline phosphatase (ALP), γ-glutamyl transferase (GT), viral hepatitis serology and hepatic auto-antibodies, vitamin B12, blood glucose, lipids and hormones.

    Results  Seventy-nine subjects (36%) had one or more liver enzyme levels higher than the reference level, the most prevalent being GT. Karyotype 45,X was present in 51% of all TS women and in 48% of those with elevated liver enzymes. Body weight, body mass index (BMI), total cholesterol, triglycerides, and apolipoproteins A and B at start were higher in TS women with elevated liver enzymes than in TS women with normal levels. At 5 years, AST, ALT and GT were increased and another 23% of patients had developed elevated liver enzymes, that is, 59% in total (36% + 23%), while in 6%, the elevated liver enzymes had been normalized and all 6% also had lowered cholesterol levels. Multivariate analysis showed that GT was correlated with total cholesterol; P = 0·0032 at start and P = 0·0005 at 5 years, independently of other factors. Liver biopsy in six TS women showed one cholangitis, one hepatitis C, two steatosis and two normal biopsies. Withdrawal of oestrogen substitution did not influence the liver enzymes.

    Conclusions  Pathological liver enzymes were common in TS women, with a prevalence of 36% at 33 years of age, an annual incidence over 5 years of 3·4%. There was no relation to karyotype, alcohol, viral hepatitis, E2 or autoimmunity, but a connection with total serum cholesterol.

  • 8. Evang, Johan Arild
    et al.
    Berg, Jens Petter
    Casar-Borota, Olivera
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Lekva, Tove
    Kringen, Marianne Kristiansen
    Ramm-Pettersen, Jon
    Bollerslev, Jens
    Reduced levels of E-cadherin correlate with progression of corticotroph pituitary tumours2011Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 75, nr 6, s. 811-818Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: Loss of E-cadherin is an important marker of epithelial tumour progression. The aims of this study were to explore whether E-cadherin expression and localization correlate to corticotroph tumour progression, relate the expression of the E-cadherin gene (CDH1) to immunohistochemical E-cadherin staining pattern, and study whether the E-cadherin levels were correlated to methylation status of the CDH1 promoter region.

    Design: Immunohistochemical analyses of E-cadherin protein were performed, as was RT-qPCR of the CDH1 and the POMC genes. Methylation pattern of the promoter region of CDH1 was measured using pyrosequencing of bisulfite-treated DNA.

    Patients: Forty-five patients operated at a tertiary referral centre in Oslo, Norway. Adenoma tissue sections and RNA samples from patients with verified Cushing's disease or Nelson's syndrome were collected.

    Measurements: Expression of E-cadherin mRNA and protein in pituitary corticotroph adenomas and average percentage of methylated cytosines in a cytosine-phosphate-guanosine island of the CDH1 promoter.

    Results: Correlations were observed between tumour progression and both nuclear expression of E-cadherin and reduced CDH1 mRNA. The E-cadherin expression was not determined by the methylation pattern of the CDH1 promoter. Conclusions Corticotroph tumour progression was associated with reduced expression of the epithelial marker E-cadherin.

  • 9. Evans, Juliet
    et al.
    Goedecke, Julia H
    Söderström, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Burén, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Alvehus, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blomquist, Caroline
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Jonsson, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hayes, Philip M
    Adams, Kevin
    Dave, Joel A
    Levitt, Naomi S
    Lambert, Estelle V
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Depot- and ethnic-specific differences in the relationship between adipose tissue inflammation and insulin sensitivity2011Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 74, nr 1, s. 51-59Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective  It is unclear whether there are differences in inflammatory gene expression between abdominal and gluteal subcutaneous adipose tissue (SAT), and between black and white women. We therefore tested the hypotheses that SAT inflammatory gene expression is greater in the abdominal compared to the gluteal depot, and SAT inflammatory gene expression is associated with differential insulin sensitivity (S(I) ) in black and white women.

    Design and methods  S(I) (frequently sampled intravenous glucose tolerance test) and abdominal SAT and gluteal SAT gene expression levels of 13 inflammatory genes were measured in normal-weight (BMI 18-25 kg/m(2) ) and obese (BMI >30 kg/m(2) ) black (n = 30) and white (n = 26) South African women.

    Results  Black women had higher abdominal and gluteal SAT expression of CCL2, CD68, TNF-α and CSF-1 compared to white women (P < 0·01). Multivariate analysis showed that inflammatory gene expression in the white women explained 56·8% of the variance in S(I) (P < 0·005), compared to 20·9% in black women (P = 0·30). Gluteal SAT had lower expression of adiponectin, but higher expression of inflammatory cytokines, macrophage markers and leptin than abdominal SAT depots (P < 0·05).

    Conclusions  Black South African women had higher inflammatory gene expression levels than white women; however, the relationship between AT inflammation and S(I) was stronger in white compared to black women. Further research is required to explore other factors affecting S(I) in black populations. Contrary to our original hypothesis, gluteal SAT had a greater inflammatory gene expression profile than abdominal SAT depots. The protective nature of gluteo-femoral fat therefore requires further investigation.

  • 10. Fougner, Stine Lyngvi
    et al.
    Casar Borota, Olivera
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Heck, Ansgar
    Berg, Jens Petter
    Bollerslev, Jens
    Adenoma granulation pattern correlates with clinical variables and effect of somatostatin analogue treatment in a large series of patients with acromegaly2012Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 76, nr 1, s. 96-102Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context Somatotroph adenomas have been classified into densely granulated (DG) and sparsely granulated (SG) tumours with a transitional, intermediate group. Gsp oncogenes are activating mutations in the Gsa subunit gene, found in approximately 40% of somatotroph adenomas.

  • 11. Heck, Ansgar
    et al.
    Ringstad, Geir
    Fougner, Stine L.
    Casar-Borota, Olivera
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Nome, Terje
    Ramm-Pettersen, Jon
    Bollerslev, Jens
    Intensity of pituitary adenoma on T2-weighted magnetic resonance imaging predicts the response to octreotide treatment in newly diagnosed acromegaly2012Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, nr 1, s. 72-78Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Primary, preoperative medical treatment is an option in selected patients with acromegaly, but a subset of patients respond poorly. Valid prediction of response to somatostatin analogues (SA) might thus alter treatment stratification. The aims of this study were to assess whether T2 signal intensity could determine long-term response to first-line SA treatment and to assess clinical and biochemical baseline characteristics, as well as histological subtype in relation to the magnetic resonance imaging (MRI) appearances. Methods In 45 newly diagnosed patients, T2-weighted signal intensity of the tumour was classified into hypo-, iso- or hyperintense. Biochemical and clinical baseline variables for the three groups were compared. In 25 patients primarily treated with long-acting SA for a median of 6 months [interquartile range (IQR):155180 days], GH and IGF-1 reduction was assessed, and in 34 cases, immunohistochemical granulation pattern was evaluated. Results The results showed that 12 (27%) adenomas were hypointense, 15 (33%) isointense and 18 (40%) hyperintense. Median IGF-1 [ratio IGF-1/ULN; (upper limit of normal)] was 3.5 (2.34.9), 2.9 (2.63.8) and 1.9 (1.32.6), respectively (P = 0.006 for difference between groups). Median GH values (mu g/l) of a 3- to 5-point profile were 17.5 (6.135), 9.3 (6.032.5) and 4.1 (1.58.3), (P = 0.025). Median IGF-1 reduction (% of baseline) after first-line SA treatment was 51 (4970), 36 (1974) and 13 (542) (P = 0.03); median reduction in GH (% of baseline) was 86 (7294), 78 (6285) and 46 (170) (P = 0.02). T2 hyperintensity was associated with sparse granulation pattern on immunohistochemistry. Conclusion In patients with acromegaly, T2 signal intensity at diagnosis correlates with histological features and predicts biochemical outcome of first-line SA treatment.

  • 12.
    Hedström, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wang, Mingde
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Gideonsson, Ida
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Turkmen, Sahruh
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Women with polycystic ovary syndrome have elevated serum concentrations of and altered GABA A receptor sensitivity to allopregnanolone2015Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 83, nr 5, s. 643-650Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    ObjectiveSeveral studies have reported that -aminobutyric acid (GABA) ergic circuits are involved in the pathophysiology of polycystic ovary syndrome (PCOS). The progesterone metabolite allopregnanolone is a potent GABA(A)-receptor-modulating steroid, and patients may have increased concentrations of allopregnanolone or altered GABA(A) receptor sensitivity. We investigated both of these possibilities in this study. PatientsWe enrolled 9 women with PCOS and 24 age-matched eumenorrhoeic controls, who were divided into two groups by body mass index (BMI) (16 normal weight and 8 overweight). MeasurementsWe investigated the effects of allopregnanolone injection on GABA(A) receptor sensitivity in both groups of women. All women received a single intravenous dose of allopregnanolone (0050mg/kg). GABA(A) receptor sensitivity was assessed with the saccadic eye velocity (SEV) over 30 degrees (SEV30 degrees), the SEV30 degrees/allopregnanolone concentration ([Allo]) ratio, and sedation, which were measured together with serum allopregnanolone at intervals for 180min after injection. The controls were tested in the follicular phase of the menstrual cycle. ResultsBaseline allopregnanolone concentrations were higher in the PCOS women than in the normal-weight (P=0034) and overweight controls (P=0004). The allopregnanolone concentrations after injection were higher in the PCOS women (P=0006) and overweight controls (P=0037) than in the normal-weight controls. All groups showed a decline in the SEV30 degrees/[Allo] ratio after injection. Allopregnanolone had a smaller effect on the SEV30 degrees/[Allo] ratio in the overweight women (PCOS, P=0032; controls, P=0007) than in the normal-weight controls. The sedation score after allopregnanolone injection was lower in the PCOS patients than in the controls, but was not different between the two control groups. ConclusionsPCOS women had elevated baseline allopregnanolone concentrations compared with follicular-phase controls. All overweight women (PCOS and controls) were less sensitive to allopregnanolone than normal-weight controls.

  • 13.
    Lindmark, Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Burén, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Eriksson, Jan W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Insulin resistance, endocrine function and adipokines in type 2 diabetes patients at different glycaemic levels: potential impact for glucotoxicity in vivo2006Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 65, nr 3, s. 301-309Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To evaluate the interplay between hyperglycaemia, insulin resistance, hormones and adipokines in patients with type 2 diabetes mellitus (T2DM). Design and methods Ten patients with T2DM with good glycaemic control (G), 10 with poor control (P) and 10 nondiabetic control subjects (C) were matched for sex (M/F 6/4), age and body mass index. A hyperinsulinaemic, euglycaemic clamp was performed and cytokines and endocrine functions, including cortisol axis activity were assessed. Results Patients with diabetes were more insulin resistant than group C, and group P exhibited the highest degree of insulin resistance ( P = 0·01, P vs C). Tumour necrosis factor (TNF)-alpha levels were elevated in patients with diabetes ( P = 0·05) and group P had the highest levels of fasting serum cortisol ( P = 0·05), nonesterified fatty acids (NEFA; P = 0·06) and C-reactive protein (CRP; P = 0·01). Adiponectin levels were lower in the P group. In partial correlation analyses, significant associations were found: glycaemic level (HbA1c) with insulin resistance, TNF-alpha, CRP and basal and ACTH-stimulated cortisol levels, insulin resistance with plasma NEFA, TNF-alpha and stimulated cortisol levels. Conclusion Poor glycaemic control in patients with T2DM was associated with insulin resistance and with elevated TNF-alpha, CRP and basal as well as stimulated cortisol levels. Inflammatory mediators, e.g. TNF-alpha, may contribute to insulin resistance in hyperglycaemic patients with T2DM and this might be a partial explanation for glucotoxicity.

  • 14.
    Norberg, Lars
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Johansson, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Rasmuson, Torgny
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Pituitary adenomas in northern Sweden. A study on therapy choices and the risk of second primary tumours2008Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 68, nr 5, s. 780-785Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To present the incidence of pituitary adenomas in northern Sweden and to determine whether the incidence of second primary tumours differs from the incidence in the general population or might be related to radiotherapy.

    DESIGN: A retrospective register study.

    PATIENTS: A total of 546 patients with pituitary adenomas were identified in the Cancer Registry of northern Sweden between 1958 and 2004. Only patients with histopathological verification and/or endocrine activity of the adenoma and more than 12 months of follow-up were included, resulting in 376 patients in the study.

    MEASUREMENTS: The number of patients receiving surgery and/or radiotherapy and presenting second primary tumours were registered. Standard incidence ratios (SIRs) between the observed and the expected incidence of second primary tumours were calculated.

    RESULTS: The total number of person-years at risk for a second primary tumour was 4730. Fifty-four out of 376 (14%) patients had 63 second primary tumours. Forty patients had second primary tumours diagnosed more than 12 months after diagnosis of the pituitary adenoma (expected 42.6, SIR 0.94, 95% CI 0.67-1.28). A significantly increased incidence of second primary tumours was seen in 42 men with GH-secreting adenomas. Ten second tumours were found (expected 4.55, SIR 2.20, 95% CI 1.05-4.04). A total of 261 patients received radiotherapy and 31 second primary tumours occurred after radiotherapy (expected 32.9, SIR 0.94, 95% CI 0.64-1.34). Three second primary intracranial tumours appeared within the irradiation volume (expected 0.85, SIR 3.51, 95% CI 0.71-10.36).

    CONCLUSIONS: No significant increase was found in the incidence of second primary tumours in general in patients with pituitary adenomas. An increased incidence of second primary tumours was seen in men with GH-secreting adenomas.

  • 15. Nygren, Anders
    et al.
    Sunnegårdh, Jan
    Teien, Dag
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Jonzon, Anders
    Björkhem, Gudrun
    Lindell, Sven
    Albertsson-Wikland, Kerstin
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Rapid cardiovascular effects of growth hormone treatment in short prepubertal children: impact of treatment duration2012Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, nr 6, s. 877-884Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective Previous studies show that growth hormone (GH) treatment increases cardiac dimensions in short children with GH deficiency (GHD) and has diverse cardiac effects in children with idiopathic short stature (ISS). This study was performed to assess the effect of GH on the cardiovascular system in short children with a broad range of GH secretion and GH sensitivity/responsiveness.

    Design and patients In this prospective, multicentre study, short prepubertal children diagnosed with isolated GHD (89) or ISS (38) were followed during 2 years of GH treatment. They were randomized to receive either a standard (43 mu g/kg/day) or an individualized GH dose (range 17100 mu g/kg/day) based on GH responsiveness estimated by a prediction model and distance to target height. Echocardiography, blood pressure and electrocardiography were performed at baseline, 3, 12 and 24 months.

    Results Left ventricular mass (LVM) indexed to body surface area increased significantly during 2 years of GH treatment in both GHD and ISS irrespective of randomized dose. This change was already apparent at 3 months, when standard deviation scores (SDS) of wall thickness and diameter were increased. At 24 months, left ventricular diameter SDS remained increased, whereas myocardial thickness SDS returned to baseline values. There was no impairment of systolic or diastolic function. There was no correlation with treatment dose and LVM SDS at 24 months.

    Conclusions Irrespective of GH status, there was a rapid increase in LVM during GH treatment in short children. At 3 months, wall thickness and diameter were increased, whereas only diameter remained increased at 24 months.

  • 16. Rask, E
    et al.
    Simonyte, Kotryna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lönn, L
    Axelson, M
    Cortisol metabolism after weight loss: associations with 11 beta-HSD type 1 and markers of obesity in women2013Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 78, nr 5, s. 700-705Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective Increased glucocorticoid metabolite excretion and enhanced expression and activity of 11-hydroxysteroid dehydrogenase type 1 in adipose tissue are closely correlated with obesity and its detrimental consequences. Weight loss ameliorates the latter. The aim of this study was to explore whether increased glucocorticoid exposure in obesity is improved with substantial weight loss and thus is a consequence rather than a cause of obesity. Design and patients A prospective cohort study in 31 women. Measurements 11-HSD type 1 expression and activity, urinary glucocorticoid metabolite excretion, body composition including regional adipose tissue depots and insulin resistance by HOMA-IR before and 2years after gastric bypass surgery. Results After weight loss, excretion of cortisol and cortisone metabolites decreased. Both cortisol and cortisone metabolite excretion correlated with central obesity, where the intraabdominal fat depot showed the strongest association. Cortisol metabolites correlated with 11-HSD type 1 activity in abdominal subcutaneous adipose tissue. The ratio of cortisol to cortisone metabolites [(5-tetrahydrocortisol (5THF)+tetrahydrocortisol (THF)+-cortol)/(tetrahydrocortisone (THE)+-cortolone)] and the ratio of 5-THF/THF both decreased after stable weight loss, reflecting a downregulation of the net activities of 11-HSD type 1 and 5-reductase. Conclusion Long-term weight loss in women is not only followed by reduced glucocorticoid production, but also favourably decreases the global and tissue-specific activity of the cortisol-activating enzyme 11 -HSD type 1, possibly contributing to the health benefits of bariatric surgery.

  • 17.
    Turkmen, Sahruh
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Hedström, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Gideonsson, Ida
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wang, Mingde
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    The author's reply: Blood allopregnanolone levels in women with polycystic ovary syndrome2016Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 85, nr 1, s. 152-154Artikkel i tidsskrift (Fagfellevurdert)
  • 18. Wake, Deborah J
    et al.
    Strand, Magnus
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Rask, Eva
    Westerbacka, Jukka
    Livingstone, Dawn E W
    Söderberg, Stefan
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin.
    Andrew, Ruth
    Yki-Jarvinen, Hannele
    Olsson, Tommy
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Walker, Brian R
    Intra-adipose sex steroid metabolism and body fat distribution in idiopathic human obesity.2007Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 66, nr 3, s. 440-446Artikkel i tidsskrift (Fagfellevurdert)
  • 19.
    Wiklund, Peder
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Högström, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Engström, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Gustafsson, Thomas
    Karolinska universitetslaboratoriet, Klinisk kemi.
    Franks, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    High impact loading on the skeleton is associated with a decrease in glucose levels in young men2012Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, nr 6, s. 823-827Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective The skeleton has been suggested to be involved in energy metabolism through osteocalcin (OC), an osteoblast-specific molecule. The objective of this study was to investigate whether high impact exercise stimulating bone formation would lead to changes in glucose and lipid metabolism independent of cardiorespiratory effects, and if OC mediates this association.

    Design Prospective intervention study.

    Methods Fifty men aged 20-32 years were allocated to an intervention group or a control group. The intervention group completed six different types of jumps in sets of five, with the frequency of these exercises gradually increasing over 8 weeks. At baseline and after 8 weeks, glycerol concentrations were measured in fat tissue as a marker of lipolysis by using microdialysis. Blood samples were assayed for OC and markers of glucose and lipid metabolism. Physical activity was measured using an accelerometer.

    Results After adjustment for confounders at baseline and changes in physical activity during the intervention period, the intervention was associated with a decrease in levels of glucose (p = 0.04), adrenalin (p = 0.03) and OC (p=0.04) after adjusting for baseline levels and changes in physical activity. No other differences between the groups were significant, although the trends of the metabolic variables favored the intervention group.

    Conclusions The results of this study suggest that high impact loading on the skeleton may affect glucose metabolism independent of the level of aerobic exercise.

  • 20. Zang, Hong
    et al.
    Moritz, Thomas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Norstedt, Gunnar
    Hirschberg, Angelica L.
    Tollet-Egnell, Petra
    Effects of oestrogen and testosterone therapy on serum metabolites in postmenopausal women2012Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, nr 2, s. 288-295Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives Metabolite profiles of body fluids or tissue extracts can be regarded as important indicators of physiological or pathological states. Whether hormone-specific alterations of the serum metabolome can be identified using this technique has not been tested yet. The aim of this study was to investigate metabolic responses during hormone therapy in postmenopausal women by a nontargeted metabolomics approach. Methods Sixty naturally postmenopausal women were randomly assigned to treatment with testosterone undecanoate 40 similar to mg every second day; estradiol valerate 2 similar to mg daily; or the combination of both. Serum metabolites were determined by gas chromatography-mass spectrometry (GC-MS) before and after 3 similar to months of treatment. Metabolites affected by the treatment were identified and correlated with changes in insulin sensitivity and lipid profiles. Results Treatment-dependent and hormone-specific effects on serum metabolites were observed, ranging between 69% reduction and 184% increase, but the metabolites that best explained the differences could not be structurally identified. Effects on annotated metabolites were less associated with clinical parameters as compared to established serum markers for adverse lipid and carbohydrate metabolism, such as cholesterol and triglycerides. However, cystine, lysine and tyrosine were shown to change in correlation with insulin sensitivity and high-density lipoprotein cholesterol levels in response to testosterone, indicating that those responses were somehow related to each other. Conclusions Oestrogen- and androgen-specific alterations in the serum metabolome could be identified using GC-MS, reflecting hormone-specific effects on whole body metabolism. New knowledge regarding steroid-mediated metabolic responses within different tissues might be obtained using a similar approach on tissue extracts.

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