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Open access

Michaela Keuper

The crosstalk between macrophages (MΦ) and adipocytes within white adipose tissue (WAT) influences obesity-associated insulin resistance and other associated metabolic disorders, such as atherosclerosis, hypertension and type 2 diabetes. MΦ infiltration is increased in WAT during obesity, which is linked to decreased mitochondrial content and activity. The mechanistic interplay between MΦ and mitochondrial function of adipocytes is under intense investigation, as MΦ and inflammatory pathways exhibit a pivotal role in the reprogramming of WAT metabolism in physiological responses during cold, fasting and exercise. Thus, the underlying immunometabolic pathways may offer therapeutic targets to correct obesity and metabolic disease. Here, I review the current knowledge on the quantity and the quality of human adipose tissue macrophages (ATMΦ) and their impact on the bioenergetics of human adipocytes. The effects of ATMΦ and their secreted factors on mitochondrial function of white adipocytes are discussed, including recent research on MΦ as part of an immune signaling cascade involved in the ‘browning’ of WAT, which is defined as the conversion from white, energy-storing adipocytes into brown, energy-dissipating adipocytes.

Open access

Eva Jakobsson Ung, Ann-Charlotte Olofsson, Ida Björkman, Tobias Hallén, Daniel S Olsson, Oskar Ragnarsson, Thomas Skoglund, Sofie Jakobsson and Gudmundur Johannsson

Objective: Experiences and need of support during surgery and start of replacement therapy in patients with pituitary tumours are highly unknown. This study therefore aimed at exploring patient experiences during pre- and postoperative care and recovery after pituitary surgery in patients with a pituitary tumour.

Methods: Within a qualitative study design, 16 consecutive patients who underwent surgery for pituitary tumours were repeatedly interviewed. In total 42 interviews were performed before and after surgery. Analysis was performed using qualitative interpretation.

Results: Suffering a pituitary tumour was overwhelming for many patients and struggling with existential issues was common. Patients expressed loneliness and vulnerability before and after surgery. How professionals handled information in connection with diagnosis greatly affected the patients. Other patients with the same diagnosis were experienced as the greatest support. Normalisation of bodily symptoms and relationships with others were reported during postoperative recovery. However, a fear that the tumour would return was present.

Conclusions: Patients with pituitary tumours need structured support, including peer support, which acknowledges physical, cognitive as well as emotional and existential concerns. Information related to diagnosis and surgery should be adapted in relation to the loneliness and the existential seriousness of the situation. Care and support for patients with pituitary tumours should preferably be organised based on continuity and an unbroken care pathway from the first pre-operative evaluation through to post-operative care and the start of a life-long endocrine treatment and tumour surveillance.

Open access

Monika Bilic, Huma Qamar, Akpevwe Onoyovwi, Jill Korsiak, Eszter Papp, Abdullah Al Mahmud, Rosanna Weksberg, Alison D Gernand, Jennifer Harrington and Daniel E Roth

Fetal growth restriction is linked to adverse health outcomes and is prevalent in low- and middle-income countries; however, determinants of fetal growth are still poorly understood. The objectives were to determine the effect of prenatal vitamin D supplementation on the insulin-like growth factor (IGF) axis at birth, to compare the concentrations of IGF-I in newborns in Bangladesh to a European reference population and to estimate the associations between IGF protein concentrations and birth size. In a randomized controlled trial in Dhaka, Bangladesh, pregnant women enrolled at 17–24 weeks of gestation were assigned to weekly oral vitamin D3 supplementation from enrolment to delivery at doses of 4200 IU/week, 16,800 IU/week, 28,000 IU/week or placebo. In this sub-study, 559 woman–infant pairs were included for analysis and cord blood IGF protein concentrations were quantified at birth. There were no significant effects of vitamin D supplementation on cord blood concentrations of IGF-I (P = 0.398), IGF-II (P = 0.525), binding proteins (BPs) IGFBP-1 (P = 0.170), IGFBP-3 (P = 0.203) or the molar ratio of IGF-I/IGFBP-3 (P = 0.941). In comparison to a European reference population, 6% of girls and 23% of boys had IGF-I concentrations below the 2.5th percentile of the reference population. IGF-I, IGF-II, IGFBP-3 and the IGF-I/IGFBP-3 ratio were positively associated with at least one anthropometric parameter, whereas IGFBP-1 was negatively associated with birth anthropometry. In conclusion, prenatal vitamin D supplementation does not alter or enhance fetal IGF pathways.

Open access

Rasha Odeh, Abeer Alassaf, Lubna Gharaibeh, Sarah Ibrahim, Fareed Khdair Ahmad and Kamel Ajlouni

Objective

Scientific findings regarding the prevalence of celiac disease (CD) in pediatric patients with type 1 diabetes (T1D) in the Arab world are scarce. We aimed to determine the prevalence of biopsy-proven celiac disease (BPCD) among pediatric patients with T1D from Jordan. We also assessed the possible predictors for developing CD in this cohort of patients and we compared T1D patients who developed BPCD with those who had positive CD serology but negative histology and/or fluctuating CD serology.

Methods

Celiac serology and duodenal biopsy results from 2012 to 2017 were collected from patients with T1D. The outcome of positive celiac serology and the risk factors for CD in T1D patients were investigated.

Results

A total of 538 children of which 278 boys (51.7%) were included in the study. The prevalence of positive serology and the diagnosis of BPCD in this cohort of T1D patients were 16.6 and 9.1% respectively. Eighty percent of those with BPCD were asymptomatic and 47% were diagnosed with CD at onset of T1D. Spontaneous normalization of celiac serology occurred in 23.6% of those with positive serology.

Conclusion

CD is prevalent in T1D pediatric patients from Jordan (9.1%). It is often asymptomatic and the majority of cases were diagnosed at onset or within 5 years of T1D diagnosis. Spontaneous normalization of CD serology occurred in some patients with T1D. Hence, a watchful follow-up is recommended in such patients.

Open access

Shuang Ye, Yuanyuan Xu, Jiehao Li, Shuhui Zheng, Peng Sun and Tinghuai Wang

The role of G protein-coupled estrogen receptor 1 (GPER) signaling, including promotion of Ezrin phosphorylation (which could be activated by estrogen), has not yet been clearly identified in triple-negative breast cancer (TNBC). This study aimed to evaluate the prognostic value of GPER and Ezrin in TNBC patients. Clinicopathologic features including age, menopausal status, tumor size, nuclear grade, lymph node metastasis, AJCC TNM stage, and ER, PR and HER-2 expression were evaluated from 249 TNBC cases. Immunohistochemical staining of GPER and Ezrin was performed on TNBC pathological sections. Kaplan–Meier analyses, as well as logistic regressive and Cox regression model tests were applied to evaluate the prognostic significance between different subgroups. Compared to the GPER-low group, the GPER-high group exhibited higher TNM staging (P = 0.021), more death (P < 0.001), relapse (P < 0.001) and distant events (P < 0.001). Kaplan–Meier analysis showed that GPER-high patients had a decreased OS (P < 0.001), PFS (P < 0.001), LRFS (P < 0.001) and DDFS (P < 0.001) than GPER-low patients. However, these differences in prognosis were not statistically significant in post-menopausal patients (OS, P = 0.8617; PFS, P = 0.1905; LRFS, P = 0.4378; DDFS, P = 0.2538). There was a significant positive correlation between GPER and Ezrin expression level (R = 0.508, P < 0.001) and the effect of Ezrin on survival prognosis corresponded with GPER. Moreover, a multivariable analysis confirmed that GPER and Ezrin level were both significantly associated with poor DDFS (HR: 0.346, 95% CI 0.182–0.658, P = 0.001; HR: 0.320, 95% CI 0.162–0.631, P = 0.001). Thus, overexpression of GPER and Ezrin may contribute to aggressive behavior and indicate unfavorable prognosis in TNBC; this may correspond to an individual’s estrogen levels.

Open access

Karim Gariani, Pedro Marques-Vidal, Gérard Waeber, Peter Vollenweider and François Jornayvaz

Background: Excessive glucocorticoid secretion has been associated with type 2 diabetes mellitus (T2DM) and other features of the metabolic syndrome. We aimed to evaluate if basal salivary cortisol may predict occurrence of new insulin resistance (IR) or T2DM.

Method: This was a prospective, population-based study derived from the CoLaus (Cohorte lausannoise) study including 1525 participants (aged 57.7 ± 10.3 y; 725 women). A total of 1149 individuals were free from diabetes at baseline. Fasting plasma glucose and insulin were measured after a follow-up of 5.3 y. Basal salivary cortisol was measured at baseline. The association between basal salivary cortisol level and incidence of IR or T2DM was analyzed by logistic regression, and the results were expressed for each independent variables as ORs and 95% CI.

Results: After a median follow-up of 5.3 y, a total of 376 subjects (24.7%) developed IR and 32 subjects (2.1%) developed T2DM. Basal salivary cortisol divided in quartiles was not associated with incidence of IR or T2DM. Multivariable analysis for age, gender, body mass index, physical activity and smoking status showed no association between basal and incidence of IR (quartile 2 (Q2) OR: 1.01 (0.70-1.45), quartile 3 (Q3) OR: 1.01 (0.70-1.45), quartile 4 (Q4) OR: 1.05 (0.73-1.52), p=0.805) or T2DM (Q2 OR: 1.00 (0.37 – 2.73), Q3 OR: 0.96 (0.35 – 2.61), Q4 OR: 1.08 (0.40 - 2.95)).

Conclusion: In the CoLaus study of healthy adults, basal salivary cortisol was not associated with incident IR or T2DM.

Open access

Shilpa Lingaiah, Laure Morin-Papunen, Terhi Piltonen, Inger Sundström-Poromaa, Elisabet Stener-Victorin and Juha S Tapanainen

Objective

Serum levels of retinol-binding protein 4 (RBP4), an adipokine thought to affect systemic insulin sensitivity, were compared between women with polycystic ovary syndrome (PCOS) and non-PCOS controls to evaluate the association of RBP4 with clinical, hormonal and metabolic parameters of PCOS.

Subjects and methods

Serum RBP4 levels were analysed in 278 women with PCOS (age range 18–57 years) and 191 non-PCOS controls (age 20–53 years) by enzyme-linked immunosorbent assay.

Results

Serum levels of RBP4 were increased in women with PCOS compared with control women in the whole population (45.1 ± 24.0 (s.d.) vs 33.5 ± 18.3 mg/L, P < 0.001). Age-stratified analysis showed that serum RBP4 levels were increased in women with PCOS aged ≤30 years compared with controls (47.7 ± 23.5 vs 27.1 ± 10.4 mg/L, P < 0.001), whereas no significant differences were seen in the other age groups. No significant correlations of RBP4 were seen with either steroids or indices of insulin resistance.

Conclusions

Although serum RBP4 levels were increased in younger women with PCOS compared with age-matched non-PCOS controls, RBP4 does not seem to be a good marker of insulin resistance or other metabolic derangements in women with PCOS.

Open access

Charlotte Höybye, Laia Faseh, Christos Himonakos, Tomasz Pielak and Jesper Eugen-Olsen

Growth hormone deficiency (GHD) syndrome is associated with adverse levels of several risk factors for cardiovascular diseases (CVD), including metabolic inflammation. However, the impact of GHD and GH treatment on low-grade inflammation is unknown. The aim of the study was to establish the level of the low-grade inflammation biomarker soluble urokinase plasminogen activator receptor (suPAR) in adults with GHD and the response to long-term GH treatment. Measurements of suPAR and CRP were performed in bio-bank serum samples from 72 adults, 34 males and 38 females, with GHD before and during at least 5 years of GH treatment. Mean age was 52.5 ± 15.5 years, BMI 27.3 ± 5 kg/m2. Clinical evaluations and blood sampling were performed at routine visits. Data on demography, anthropometry, lab results and clinical events were retrieved from post-marketing surveillance study databases and medical records. suPAR and high-sensitive (hs) CRP were analysed using ELISA and immunochemistry, respectively. At baseline blood pressure, lipid profile and fasting glucose were within the normal reference range. Baseline geometric mean and 95% CI of suPAR was 2.9 (2.7–3.3) ng/mL and of CRP 2.3 (0.6–4.0) mg/L. Mean follow-up was 8 ± 2 years. The suPAR levels remained stable during follow-up, although individual increases were seen on occurrence or presence of co-morbidities. In contrast, levels of CRP decreased. In conclusion, the decrease in CRP and indirectly the absence of an expected increase in suPAR over time indicates a favourable effect of GH on low-grade inflammation.

Open access

Jeremy Turner, Neil Gittoes, Peter Selby and the Society for Endocrinology Clinical Committee

Open access

Barbora Pekova, Sarka Dvorakova, Vlasta Sykorova, Gabriela Vacinova, Eliska Vaclavikova, Jitka Moravcova, Rami Katra, Petr Vlcek, Pavla Sykorova, Daniela Kodetova, Josef Vcelak and Bela Bendlova

There is a rise in the incidence of thyroid nodules in pediatric patients. Most of them are benign tissues, but part of them can cause papillary thyroid cancer (PTC). The aim of this study was to detect the mutations in commonly investigated genes as well as in novel PTC-causing genes in thyroid nodules and to correlate the found mutations with clinical and pathological data. The cohort of 113 pediatric samples consisted of 30 benign lesions and 83 PTCs. DNA from samples was used for next-generation sequencing to identify mutations in the following genes: HRAS, KRAS, NRAS, BRAF, IDH1, CHEK2, PPM1D, EIF1AX, EZH1 and for capillary sequencing in case of the TERT promoter. RNA was used for real-time PCR to detect RET/PTC1 and RET/PTC3 rearrangements. Total detection rate of mutations was 5/30 in benign tissues and 35/83 in PTCs. Mutations in RAS genes (HRAS G13R, KRAS G12D, KRAS Q61R, NRAS Q61R) were detected in benign lesions and HRAS Q61R and NRAS Q61K mutations in PTCs. The RET/PTC rearrangement was identified in 18/83 of PTCs and was significantly associated with higher frequency of local and distant metastases. The BRAF V600E mutation was identified in 15/83 of PTCs and significantly correlated with higher age of patients and classical variant of PTC. Germline variants in the genes IDH1, CHEK2 and PPM1D were found. In conclusion, RET/PTC rearrangements and BRAF mutations were associated with different clinical and histopathological features of pediatric PTC. RAS mutations were detected with high frequency in patients with benign nodules; thus, our results suggest that these patients should be followed up intensively.