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  • 1
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    β-cell dysfunction in women with previous gestational diabetes is associated with visceral adipose tissue distribution
    Oxford University Press (OUP) ; 2015
    In:  European Journal of Endocrinology Vol. 173, No. 1 ( 2015-07), p. 63-70
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 173, No. 1 ( 2015-07), p. 63-70
    Abstract: Glucose intolerance in pregnancy predicts an increased risk of future type 2 diabetes. Objective The aim of the study was to evaluate glucose metabolism in women with and without gestational diabetes mellitus (GDM) at 5 years follow-up and identify risk factors associated with disturbed glucose metabolism post-partum . Design This follow-up study included 300 consecutively enrolled women from a previous population-based cohort study. The participants underwent oral glucose tolerance test under pregnancy and in the follow-up study, in addition to dual-energy X-ray absorptiometry in the follow-up study. Results Fifty-two women (17.7%) were found to have GDM in pregnancy with an odds ratio of 4.8 developing prediabetes 5 years later. β-cell function, but not insulin resistance or sensitivity, was reduced in the follow-up study after adjusting for known risk factors. Furthermore, visceral fat content at follow-up was increased in GDM women compared to non-GDM women, and the β-cell function declined with increasing visceral fat in both groups but was more pronounced in the women with previous GDM. Conclusions Women with GDM are at increased risk of developing prediabetes and have a decreased β-cell function 5 years post-partum that is associated with increased visceral fat mass.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-15-0153
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 1485160-X
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  • 2
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    Treatment with the PPARγ agonist rosiglitazone downregulates interleukin-1 receptor antagonist in individuals with metabolic syndrome
    Oxford University Press (OUP) ; 2010
    In:  European Journal of Endocrinology Vol. 162, No. 2 ( 2010-02), p. 267-273
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 162, No. 2 ( 2010-02), p. 267-273
    Abstract: Thiazolidinediones (TZDs) reduce insulin resistance, but also have pleiotropic properties including effects on inflammation. The balance between protective and proatherogenic effects may differ in various patient populations. We studied the effect of rosiglitazone on inflammatory markers in patients with metabolic syndrome (MetSyn). Methods In a cross-over randomized controlled trial, 23 subjects with MetSyn were assigned to treatment with rosiglitazone that was uptitrated from 4 mg/day for 6 weeks followed by 8 mg/day for 6 weeks or matching placebo for 12 weeks, and then to the opposite treatment for 12 weeks. Plasma levels of inflammatory and metabolic markers were measured during follow-up. Results Our main findings were i) compared to placebo, rosiglitazone significantly decreased the plasma levels of the naturally occurring interleukin (IL)1 inhibitor, IL1 receptor antagonist (IL1Ra; P =0.001), potentially reflecting inflammatory effects on the IL1 system; ii) parallel to this, rosiglitazone decreased plasma levels of IL10 ( P =0.029) further suggesting inflammatory effects; iii) rosiglitazone decreased uric acid levels ( P =0.001), and monocyte chemoattractant protein-1 ( P =0.05) and C-reactive protein ( P =0.06) tended to be lower after rosiglitazone than placebo, suggesting potential pro- and anti-inflammatory effects simultaneously and iv) in vitro , rosiglitazone enhanced IL1Ra and decreased IL1β in THP-1 monocytes, illustrating the complex effects of these medications, potentially exhibiting anti-inflammatory effects on the IL1 system in certain tissues or cells at least at certain concentrations. Conclusion Our findings suggest inflammatory effects on the IL1 system during rosiglitazone therapy in MetSyn. However, anti-inflammatory effects were also observed, and the net effect of TZDs in MetSyn should be further investigated.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-09-0706
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2010
    detail.hit.zdb_id: 1485160-X
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  • 3
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    Umbilical cord levels of sclerostin, placental weight, and birth weight are predictors of total bone mineral content in neonates
    Oxford University Press (OUP) ; 2013
    In:  European Journal of Endocrinology Vol. 168, No. 3 ( 2013-03), p. 371-378
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 168, No. 3 ( 2013-03), p. 371-378
    Abstract: During pregnancy, changes occur in the maternal calcium homeostasis to fulfill fetal demand. We hypothesized that the fibroblast growth factor 23 (FGF23) system and Wnt signaling pathway are important for normal skeletal development in the offspring. Aims Circulating α-klotho, FGF23, sclerostin, and 25-hydroxyvitamin D (25(OH)D) at the fetal and maternal sides of the placenta were measured to investigate associations with newborn bone mass independent of maternal BMI, calcium and phosphate levels, placental weight, and birth weight. Methods In a prospective cohort of healthy pregnant women, the total body bone mineral content (BMC) in 202 newborns was measured by dual-energy X-ray absorptiometry. Maternal circulating levels of the biomarkers were measured at gestational weeks 30–32 and in umbilical cord plasma (UCP) at birth. Results Mean α-klotho and sclerostin concentrations in the UCP were significantly higher than maternal levels (3004 vs 1077 pg/ml; P 〈 0.001 and 629 vs 346 pg/ml; P 〈 0.001 respectively), and mean 25(OH)D was lower (31 vs 45 nmol/l; P 〈 0.001). The UCP and maternal FGF23 levels were similar. No significant effects of maternal biomarkers on BMC were found in regression analyses. Among UCP biomarkers, only UCP sclerostin was significantly associated with BMC in univariate analyses, and the effect remained significant after adjustment for birth weight and other confounders. Conclusions We found that UCP sclerostin levels, birth weight, and placental weight were significant predictors of neonatal BMC but found no evidence for a main role of maternal levels of α-klotho, FGF23, sclerostin, or 25(OH)D nor of UCP levels of α-klotho, FGF23, or 25(OH)D.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-12-0531
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2013
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  • 4
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    Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients
    Proceedings of the National Academy of Sciences ; 2020
    In:  Proceedings of the National Academy of Sciences Vol. 117, No. 40 ( 2020-10-06), p. 25018-25025
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 40 ( 2020-10-06), p. 25018-25025
    Abstract: Respiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we describe systemic complement activation and its association with development of respiratory failure. Clinical data and biological samples were obtained at admission, days 3 to 5, and days 7 to 10. Respiratory failure was defined as PO 2 /FiO 2 ratio of ≤40 kPa. Complement activation products covering the classical/lectin (C4d), alternative (C3bBbP) and common pathway (C3bc, C5a, and sC5b-9), the lectin pathway recognition molecule MBL, and antibody serology were analyzed by enzyme-immunoassays; viral load by PCR. Controls comprised healthy blood donors. Consistently increased systemic complement activation was observed in the majority of COVID-19 patients during hospital stay. At admission, sC5b-9 and C4d were significantly higher in patients with than without respiratory failure ( P = 0.008 and P = 0.034). Logistic regression showed increasing odds of respiratory failure with sC5b-9 (odds ratio 31.9, 95% CI 1.4 to 746, P = 0.03) and need for oxygen therapy with C4d (11.7, 1.1 to 130, P = 0.045). Admission sC5b-9 and C4d correlated significantly to ferritin ( r = 0.64, P 〈 0.001; r = 0.69, P 〈 0.001). C4d, sC5b-9, and C5a correlated with antiviral antibodies, but not with viral load. Systemic complement activation is associated with respiratory failure in COVID-19 patients and provides a rationale for investigating complement inhibitors in future clinical trials.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2010540117
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 5
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    Long-term Depot Specific Changes in Adipose Tissue after Treatment of Acromegaly
    Oxford University Press (OUP) ; 2024
    In:  European Journal of Endocrinology
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP)
    Abstract: Patients with active acromegaly present a decreased adipose tissue (AT) mass, and short-term studies show that treatment leads to AT depot specific gain. However, it remains unclear if the increase is persistent in the long-term perspective and/or is sex dependent. Design To characterize the depot specific changes of AT after treatment of acromegaly and identify contributing factors. Methods Adipose tissue, including visceral (VAT), subcutaneous (SAT), total (TAT) and android to gynoid ratio (A/G ratio) were measured by Dual Energy X-ray Absorptiometry (DXA) at diagnosis (n=62), and after treatment at short-term (median (IQR) 1.9 (1.5-2.3)) and long-term 5.5 (3.9-9.5) years, and correlated to clinical and biochemical measurements. Growth hormone (GH), insulin-like growth factor I (IGF-1), glucose and HbA1c levels, gonadal status, and the presence of diabetes mellitus were recorded. Remission status was assessed at the long-term visit (IGF-1/ULN≤1.3). Differences in the temporal course of AT from baseline to short- and long-term follow-up according to sex, diabetes, gonadal and remission status were evaluated by mixed model analysis, adjusted for age. Results Despite a stable body mass index, VAT and A/G ratio increased at both time points, whereas SAT mainly increased at short-term, plateauing afterwards (p & lt;0.05 for all). VAT and A/G ratio were higher in men (p=0.035 and p & lt;0.001), and the A/G ratio increased more than in women (p=0.003). Glucose and HbA1c decreased short-term (p & lt;0.05) and remained stable at long-term. The increase in AT depots correlated with the decrease of disease activity at long-term. Remission status had no effect on changes in AT mass during follow-up. Conclusion Treatment of acromegaly leads to an increase in AT mass in a depot and sex specific manner both at short-term and long-term follow-up. Glucose metabolism improves rapidly after disease control and persists.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1093/ejendo/lvae016
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
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  • 6
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    Increased serum and bone matrix levels of transforming growth factor β1 in patients with GH deficiency in response to GH treatment
    Oxford University Press (OUP) ; 2011
    In:  European Journal of Endocrinology Vol. 165, No. 3 ( 2011-09), p. 393-400
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 165, No. 3 ( 2011-09), p. 393-400
    Abstract: Patients with adult onset GH deficiency (aoGHD) have secondary osteoporosis, which is reversed by long-term GH substitution. Transforming growth factor β1 (TGFβ1 or TGFB1) is abundant in bone tissue and could mediate some effects of GH/IGFs on bone. We investigated its regulation by GH/IGF1 in vivo and in vitro . Design and methods The effects of GH substitution (9–12 months, placebo controlled) on circulating and cortical bone matrix contents of TGFβ1 were investigated in patients with aoGHD. The effects of GH/IGF1 on TGFβ1 secretion in osteoblasts (hFOB), adipocytes, and THP-1 macrophages as well as the effects on release from platelets were investigated in vitro . Results In vivo GH substitution increased TGFβ1 protein levels in cortical bone and serum. In vitro , GH/IGF1 stimulation induced a significant increase in TGFβ1 secretion in hFOB. In contrast, no major effect of GH/IGF1 on TGFβ1 was found in adipocytes and THP-1 macrophages. Finally, a minor modifying effect on SFLLRN-stimulated platelet release of TGFβ1 was observed in the presence of IGF1. Conclusion GH substitution increases TGFβ1 in vivo and in vitro , and this effect could contribute to improved bone metabolism during such therapy, potentially reflecting direct effect of GH/IGF1 on bone cells.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-11-0442
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2011
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  • 7
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    Inflammatory adipokines contribute to insulin resistance in active acromegaly and respond differently to different treatment modalities
    Oxford University Press (OUP) ; 2014
    In:  European Journal of Endocrinology Vol. 170, No. 1 ( 2014-01), p. 39-48
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 170, No. 1 ( 2014-01), p. 39-48
    Abstract: Active acromegaly is associated with insulin resistance, but it is uncertain whether inflammation in adipose tissue is a contributing factor. Aim To test if GH/IGF1 promotes inflammation in adipocytes, and if this is relevant for systemic insulin resistance in acromegaly. Furthermore, to investigate the effect of treatment modalities (transsphenoidal surgery (TS), somatostatin analogs (SAs), and pegvisomant (PGV)) on glucose metabolism and inflammatory biomarkers in acromegaly. Methods The in vitro effects of GH/IGF1 on gene expression of adipokines in human adipocytes were investigated. Body composition, glucose metabolism, and circulating adipokines (adiponectin (AD), high-molecular weight AD (HMWAD), leptin, vascular endothelial growth factor-A (VEGF-A), monocyte chemotactic protein 1 (MCP1), and thioredoxin (TRX)) were measured in 37 patients with active acromegaly before and after treatment. Results In vitro GH, but not IGF1, increased VEGF and MCP1 in human adipocytes. In all treatment groups, body fat increased and IGF1 decreased to the same extent. Fasting glucose decreased in the TS ( P =0.016) and PGV ( P =0.042) groups, but tended to increase in the SA group ( P =0.078). Insulin and HOMA-IR decreased in both TS and SA groups, while the PGV group showed no changes. Serum VEGF and MCP1 decreased significantly in the TS group only ( P =0.010, P =0.002), while HMWAD increased with PGV treatment only ( P =0.018). A multivariate analysis model identified the changes in GH and VEGF as predictors of improvement in HOMA-IR after treatment ( R 2 =0.39, P =0.002). Conclusions i) GH directly promotes inflammation of human adipocytes by increasing VEGF and MCP1 levels; ii) glucose metabolism and inflammation (VEGF and MCP1) improve to some extent after treatment, despite an increase in adipose tissue mass; and iii) the decrease in insulin resistance after therapy in acromegaly depends, to some extent, on treatment modalities.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-13-0523
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2014
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  • 8
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    Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing’s syndrome: A prospective, long-term study
    Oxford University Press (OUP) ; 2006
    In:  European Journal of Endocrinology Vol. 154, No. 1 ( 2006-01), p. 109-118
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 154, No. 1 ( 2006-01), p. 109-118
    Abstract: Objective : Endogenous Cushing’s syndrome (CS) is associated with bone loss and an increased risk of fractures. However, the long-term outcome of treatment on bone health has not been adequately clarified. Design : We followed 33 patients with active CS prospectively before and twice after treatment (mean follow-up 33 ( n = 25) and 71 months ( n = 18), respectively). The patients were compared to age-, sex- and body mass index (BMI)-matched controls, also followed longitudinally. Methods : Bone mineral indices (bone mineral density (BMD), bone mineral content (BMC) and bone area) were evaluated in the lumbar spine (LS), femoral neck (FN), and total body (TB) by dual-energy X-ray absorptiometry (DXA). Biochemical markers of bone turnover were assessed by serum levels of osteocalcin and C-terminal telopeptides of Type-1 collagen (CTX-1). Results : Mann–Whitney rank sum tests showed that BMD of the LS, FN and TB was reduced by 14.8% ( P 〈 0.001), 15.7% ( P 〈 0.001), and 9.2% ( P 〈 0.001) in CS vs. controls at baseline, with markedly reduced serum osteocalcin ( P = 0.014) and increased CTX-1 ( P = 0.012) levels, but no correlation between markers. At first follow-up, BMD was increased in LS (7.9%, P 〈 0.001) and FN (3.5%, P = 0.003) compared to baseline. The time-dependent rise in BMD (LS ( r = 0.59; P = 0.002) and FN ( r = 0.52; P = 0.007); Spearman’s rank correlation), in CS was paralleled by increased osteocalcin (275%, P 〈 0.001) and correlation between biochemical markers ( r = 0.92, P 〈 0.001; Pearson’s correlation). TB BMD did not increase significantly before the second follow-up, when BMD Z-scores were normalized in all three compartments. Conclusion : Our observations demonstrate restoration of coupled bone remodeling and normalization of bone mineral density in all measured skeletal compartments of treated CS patients after prolonged recovery, first significant in predominantly trabecular bone (i.e. lumbar spine).
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/eje.1.02067
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2006
    detail.hit.zdb_id: 1485160-X
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  • 9
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    Positive effects of a physiological dose of GH on markers of atherogenesis: a placebo-controlled study in patients with adult-onset GH deficiency
    Oxford University Press (OUP) ; 2006
    In:  European Journal of Endocrinology Vol. 154, No. 4 ( 2006-04), p. 537-543
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 154, No. 4 ( 2006-04), p. 537-543
    Abstract: Objective : GH deficiency is associated with an increased cardiovascular mortality. Fifty-five patients with adult-onset GH deficiency (AO-GHD) (24 female, 31 male, mean age 49 years) were enrolled in a placebo-controlled double-blind crossover study to investigate the effects of GH therapy on a variety of cardiovascular risk factors representing different aspects of atherogenesis, including apolipo-proteins (Apo A-1, Apo B), markers of subclinical inflammation (high-sensitivity C-reactive protein (CRP) and interleukin-6) and markers of endothelial function (intercellular adhesion molecule-1, von Willebrand factor and sCD40L (a pro-atherogenic factor and marker for plaque destabilization)). Methods : GH therapy was individually dosed to obtain an IGF-I concentration within the normal range for age and sex. GH and placebo were administered for 9 months each, separated by a 4 month washout period. Results : The final mean dose of GH was 50% higher for women and IGF-I increased to the same level in both sexes. Compared with placebo, substitution with GH showed a significant effect on Apo B (mean change −0.15 (−0.22 to −0.08) mg/l) and CRP (−1.8 (−3.3 to −0.3) mg/l). The baseline level of and change in IGF-I during treatment with GH contributed significantly to the improvement in both markers. No effects were found on interleukin-6 or Apo A-1, or on markers of endothelial function. No gender differences were observed for any of the markers at baseline or following intervention. Conclusions : GH substitution to naïve patients with AO-GHD at a low, individually titrated dose aiming at normalizing IGF-I was followed by significant reductions in Apo B and CRP, indicating a positive effect of GH on cardiovascular risk.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/eje.1.02125
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2006
    detail.hit.zdb_id: 1485160-X
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  • 10
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    Gene expression profiling of subcutaneous adipose tissue reveals new biomarkers in acromegaly
    Oxford University Press (OUP) ; 2023
    In:  European Journal of Endocrinology Vol. 188, No. 3 ( 2023-03-02), p. 310-321
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 188, No. 3 ( 2023-03-02), p. 310-321
    Abstract: Active acromegaly is characterized by lipolysis-induced insulin resistance, which suggests adipose tissue (AT) as a primary driver of metabolic aberrations. Objective To study the gene expression landscape in AT in patients with acromegaly before and after disease control in order to understand the changes and to identify disease-specific biomarkers. Methods RNA sequencing was performed on paired subcutaneous adipose tissue (SAT) biopsies from six patients with acromegaly at time of diagnosis and after curative surgery. Clustering and pathway analyses were performed in order to identify disease activity-dependent genes. In a larger patient cohort (n = 23), the corresponding proteins were measured in serum by immunoassay. Correlations between growth hormone (GH), insulin-like growth factor I (IGF-I), visceral AT (VAT), SAT, total AT, and serum proteins were analyzed. Results 743 genes were significantly differentially expressed (P-adjusted & lt; .05) in SAT before and after disease control. The patients clustered according to disease activity. Pathways related to inflammation, cell adhesion and extracellular matrix, GH and insulin signaling, and fatty acid oxidation were differentially expressed. Serum levels of HTRA1, METRNL, S100A8/A9, and PDGFD significantly increased after disease control (P & lt; .05). VAT correlated with HTRA1 (R = 0.73) and S100A8/A9 (R = 0.55) (P & lt; .05 for both). Conclusion AT in active acromegaly is associated with a gene expression profile of fibrosis and inflammation, which may corroborate the hyper-metabolic state and provide a means for identifying novel biomarkers.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1093/ejendo/lvad031
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1485160-X
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