Résumé
Objective:The aim of this study was to examine the change of serum bone-derived hormones osteocalcin and lipocalin 2 (LCN2) level in patients with active acromegaly, and to further investigate the potential role of osteocalcin and LCN2 in glucose metabolism.Methods:Fifty consecutive patients diagnosed as acromegaly in Nanjing Drum Tower Hospital from December 2016 to August 2018 were recruited. Of those, 41 patients after operations with complete follow-up data were also included. 30 sex, age, and body mass index matched healthy persons as normal controls. Serum osteocalcin and LCN2 levels were compared between controls and patients with acromegaly, as well as at pre- and post- operation periods. Univariate and multivariate linear regression analyses were used to investigate the correlation between bone-derived hormones and glucose metabolism indexes and to determine the independent associations between variables.Results:Compared with normal controls, serum osteocalcin increased [(55.45±34.02 vs 19.46±6.69)ng/ml, P<0.01] and LCN2 levels decreased [(34.15±9.95 vs 57.50±29.75)ng/ml, P<0.01] in patients with acromegaly. Homeostasis model assessment for insulin resistance (HOMA-IR) was also elevated ( P<0.01), but homeostasis model assessment for β cell function (HOMA-β) and area under curve of insulin during 0-120 min of the oral glucose tolerance test (AUC INS) changed non-significantly in acromegaly compared to normal controls ( P>0.05). After operation, with the decrease of serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1), serum osteocalcin level decreased [24.79(18.39, 32.59) vs 43.51(26.73, 65.66)ng/ml, P<0.01] and LCN2 level increased [(45.15±15.33 vs 37.03±9.73)ng/ml, P<0.05] significantly compare to pre-operation levels. In a multivariate linear stepwise regression analysis, lean mass was shown to be the only positive predictor for LCN2 ( β=0.44, P=0.015) and elevated serum IGF-1 was a positive predictor for osteocalcin ( β=0.512, P<0.01). In the multivariate models, low LCN2 ( β=-0.398, P=0.017) and elevated serum osteocalcin ( β=0.553, P=0.001) were predictors for AUC INS, osteocalcin was a positive predictor of HOMA- β ( β=0.519, P=0.004). GH ( β=0.294, P=0.029) and IGF-1( β = 0.428, P=0.002) were all identified as positive predictors of HOMA-IR during multivariate testing in acromegaly patients. Conclusions:Acromegaly patients had increased osteocalcin and decreased LCN2 serum levels, and corresponding alteration was detected with the correction of biochemical abnormalities. Serum osteocalcin and LCN2 were predictors of β-cell function in acromegaly patients. This study adds new evidence for the role of bone in regulating glucose metabolism in acromegaly.
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Objective To investigate the frequencies of the impaired glucose tolerance and diabetes mellitus in a large cohort of active acromegaly and to identify risk factors associated with the presence of diabetes at diagnosis in these patients.Methods This study included 88 patients with newly diagnosed acromegaly.Patients were further divided into normal glucose tolerance (NGT),impaired glucose regulation (IGR),and diabetes (DM) groups according to oral glucose tolerance test or previous history.Insulin sensitivity and β cell function were also evaluated by homeostasis model assessment (HOMA).Logistic regression analysis was used to explore the independent risk factors for diabetes in patients with acromegaly.Results Impaired glucose regulation was found in 25 (28.4％),and DM in 37(42.0％) acromegaly patients.Compared to NGT and IGR patients,higher proportion of DM patients had family history of diabetes (P＜0.05).Compared to NGT group,higher post-OGTT growth hormone (GH) levels were detected in IGR and DM groups.Insulin-like growth factor 1 (IGF-1) levels were higher in IGR group while lower in DM group (P＜0.01).Homeostasis model assessment for β cell function (HOMA-β) was slightly higher in IGR group,but significantly lower in DM group (P ＜ 0.01).Homeostasis model assessment for insulin resistance (HOMA-IR) was slightly higher in IGR and DM groups but without significant difference among 3 groups.In multivariate analyses,family history of diabetes(OR=12.710,95％ CI 1.176-137.30,P=0.036),age(OR=1.106,95％ CI 1.018-1.202,P=0.017),and GH levels(OR=1.075,95％ CI 1.007-1.147,P=0.030) were independent risk factors of diabetes in acromegaly patients.Conclusion Impaired glucose metabolism is present in nearly 70％ of patients at diagnosis of acromegaly,and is associated with age,family history of diabetes,and higher GH levels,but not with IGF-1 levels.
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Objective To understand and compare the proportion of neural stem cells (NSCs) in the whole brain and cerebral cortex of mice at different embryonic days, and provide quantitative data for the later optimization of NSCs isolation and culture.Methods The whole brains (at embryonic 12.5, 14, 16 and 18 days) and cerebral cortex (at embryonic14, 16 and 18 days) were isolated and digested into single cell suspension, and were adherently cultured for 3-4 h.Immunofluorescence staining of Nestin, a NSCs specific marker, was used to statistically analyze the proportion of NSCs in each group.Expression of Nestin mRNA in the cerebral cortex of mice at E12.5, E14, E16, and E18 was detected by real-time fluorescence quantitative PCR.Results The result of immunofluorescence assay showed that there were Nestin-positive cells in the whole brain and cerebral cortex of mice at different embryonic days.In the whole brain,the proportion of NSCs was highest at E12.5 (53.42±1.57%) and lowest at E18(25.96±1.31%), and the proportions at E14 and E16 were placed in the middle among the groups.In the cerebral cortex, the highest proportion of NSCs was at E14 (33.65±0.29%), and the lowest at E18(25.29±0.28%), and the middle at E16 (26.82±0.30%).The result of real-time PCR showed that when the mRNA expression of Nestin in the cerebral cortex was set to 1, the relative mRNA expression of Nestin was 0.83±0.04 at E14, 0.77±0.05 at E16, and 0.44 ±0.05 at E18.Thus, the mRNA expression level of Nestin in the mouse cerebral cortex was gradually decreasing with the increase of embryonic days.Conclusions During the brain development, the proportion of NSCs is gradually decreasing in the whole brain and cerebral cortex of mice with the increase of embryonic days.