Previous studies found conflicting results about the associations between the exposure to hyperglycemia in utero and the later risks of childhood overweight and obesity. The aim of the present study is to compare the children’s BMI growth between offspring exposed to maternal gestational diabetes mellitus (GDM) and those not exposed and assess the associations between maternal GDM and their offspring’s overweight and obesity risk. We performed a large observational study in 1156 women and their offspring (578 GDM and 578 non-GDM mother–child pairs, matched by their offspring’s gender and age). Maternal GDM was diagnosed according to the World Health Organization criteria. Childhood height, weight, waist circumference, body fat and skinfold were measured using standardized methods. After adjustment for maternal and children’s characteristics, children born to mothers with GDM during pregnancy had higher mean values of Z scores for BMI-for-age, Z scores for weight-for-age, waist circumferences, body fat, subscapular skinfold and suprailiac skinfold, in comparison with their counterparts born to mothers with normal glucose during pregnancy (all P values <0.05). Moreover, maternal GDM was associated with a higher risk of childhood overweight and obesity with multivariate-adjusted odds ratios of 1.42 (95% confidence interval (CI): 1.02–1.97) and 1.18 (95% CI: 1.11–1.24), respectively, compared with the children of mothers without GDM during pregnancy. This study demonstrates that maternal GDM is an independent risk factor of childhood overweight and obesity and is associated with higher BMI in the offspring.
Jing Wang, Leishen Wang, Huikun Liu, Shuang Zhang, Junhong Leng, Weiqin Li, Tao Zhang, Nan Li, Wei Li, Andrea A Baccarelli, Lifang Hou, and Gang Hu
Iulia Soare, Anca Sirbu, Mihai Mircea Diculescu, Bogdan Radu Mateescu, Cristian Tieranu, Sorina Martin, Carmen Gabriela Barbu, Mirela Ionescu, and Simona Fica
Background and aim
Low bone mineral density (BMD) is a common complication in patients with inflammatory bowel disease (IBD). However, debates are ongoing with regard to the other involved factors, especially in younger patients. This study aimed to evaluate the parameters that contribute to decreased BMD, focusing on premenopausal women and men aged <50 years.
This study included 81 patients with IBD and 81 age-, sex- and BMI-matched controls. Blood tests were conducted on IBD patients, and a dual-energy X-ray absorptiometry (DXA) scan was performed on both groups.
Low BMD and fragility fracture were found to be more prevalent in IBD patients than in healthy subjects (49.3% vs 23.4%, P = 0.001 and 9.8% vs 1.2%, P = 0.01, respectively). Patients with low BMD were older, with a longer disease duration, higher faecal calprotectin (FC) levels and lower magnesium and lean mass (appreciated as appendicular skeletal muscle index (ASMI)). Multiple regression analysis revealed that ASMI, age and use of glucocorticoids were the independent parameters for decreased BMD. Although 91.3% of the patients had a 25-hydroxy vitamin D level of <30 ng/mL, it was not a statistically significant factor for decreased BMD.
In our study, the levels of vitamin D did not seem to have an important impact on BMD. Conversely, FC, magnesium and lean mass are important factors, suggesting that good control of disease, adequate magnesium intake and increased lean mass can have a good impact on bone metabolism in patients with IBD.
David Mark Robertson, Chel Hee Lee, and Angela Baerwald
It is recognised that ovarian factors, including steroid and protein hormones, are critical in the feedback regulation of pituitary gonadotropins; however, their individual contributions are less defined. The aim of this study was to explore the reciprocal relationships between ovarian and pituitary hormones across the normal ovulatory menstrual cycle as women age. FSH, LH, oestradiol, progesterone, inhibin A, inhibin B and anti-mullerian hormone (AMH) were measured in serum collected every 1–3 days across one interovulatory interval (IOI) from 26 healthy women aged 18–50 years. The antral follicle count (AFC) for follicles 2–5 mm, >6 mm and 2–10 mm were tabulated across the IOI. Independent associations between ovarian hormones/AFC vs pituitary follicle-stimulating hormone (FSH) and luteinising hormone (LH) were investigated using multivariate regression analysis. The data were sub-grouped based on the presence or absence luteal phase-dominant follicles (LPDF). Serum oestradiol and AMH were inversely correlated with FSH in both follicular and luteal phases. Inhibin B correlated inversely with FSH and LH in the late follicular phase and directly in the luteal phase. AFC, inhibin A and progesterone were not key predictors of either FSH or LH. The strong association between AMH and FSH with age implies that AMH, as well as oestradiol and inhibin B are important regulators of FSH. The change in feedback response of inhibin B with both FSH and LH across the cycle suggests two phases of the negative feedback.
Teodoro Durá-Travé, Fidel Gallinas-Victoriano, María Malumbres-Chacon, Lotfi Ahmed-Mohamed, María Jesús Chueca -Guindulain, and Sara Berrade-Zubiri
The objective of this study was to analyze whether some auxological characteristics or a single basal gonadotropin measurement will be sufficient to distinguish the prepubertal from pubertal status.
Auxologycal characteristics were recorded and serum LH and FSH were measured by immunochemiluminescence assays before and after GnRH stimulation test in a sample of 241 Caucasian girls with breast budding between 6- and 8-years old. Peak LH levels higher than 5 IU/L were considered a pubertal response. Area under the curve, cut-off points, sensitivity, and specificity for auxologycal variables and basal gonadotropins levels were determined by receiver operating curves.
There were no significant differences in age at onset, weight, height, BMI and height velocity between both groups. Bone age was significantly higher in pubertal girls (P < 0.05), although with limited discriminatory capacity. The sensitivity and specificity for the basal LH levels were 89 and 82%, respectively, for a cut off point of 0.1 IU/L. All girls in the pubertal group had a basal LH higher than 1.0 IU/L (positive predictive value of 100%). There was a wide overlap of basal FSH and LH/FSH ratio between prepubertal and pubertal girls.
Auxologycal characteristics should not be used only in the differential diagnosis between prepubertal from pubertal status in 6- to 8-year-old girls. We found a high specificity of a single basal LH sample and it would be useful for establishing the diagnosis of puberty in this age group, reducing the need for GnRH stimulation testing.
Xi Wang and Qi Yu
To evaluate the safety and efficacy of letrozole in girls with progressive precocious puberty (PP) associated with McCune–Albright syndrome (MAS).
Monocentric retrospective cross-sectional and longitudinal study of consecutive patients.
Ten MAS patients treated at Peking Union Medical College Hospital between September 1999 and December 2017 were retrospectively reviewed; those with complications due to PP were followed.
The mean age at letrozole initiation was 4.5 ± 2.6 years, while the mean duration of treatment was 3.3 ± 2.4 years. Letrozole was highly effective at decreasing the rate of skeletal maturation, with a significant decrease in the bone age-to-chronological age (BA/CA) ratio from 1.9 ± 1.1 pre-treatment to 1.5 ± 1.2 on letrozole treatment (P = 0.016). Moreover, growth velocity Z-scores declined from 0.41 ± 0.5 to −0.2 ± 0.31 with treatment (P < 0.001). Predicted adult height Z-scores increased significantly from −2.03 ± 2.33 at baseline to 1.13 ± 0.84 following treatment initiation (P = 0.029). Moreover, vaginal bleeding declined significantly on letrozole.
Our findings suggest that letrozole may be an effective therapy in some girls with MAS, as treatment results in improved BA/CA ratio, growth velocity and predicted adult height. Possible adverse effects include nettle rash.
Xue-Jiao Yang, Le-Yang Zhang, Qing-Hua Ma, Hong-Peng Sun, Yong Xu, Xing Chen, and Chen-Wei Pan
We aimed to examine the associations of platelet parameters with the presence of metabolic syndrome in community-dwelling older Chinese adults.
Study sample was from the Weitang Geriatric Diseases Study, which included 4338 individuals aged 60 years or above. The mean age of the participants was 68 years. Metabolic syndrome was defined based on the Adult Treatment Panel III criteria. Platelet parameters were assessed using an automated hematology analyzer. Multiple logistic regression models were fitted to examine relationships between the platelet parameters and the presence of metabolic syndrome after adjusting for potential confounders.
The adjusted odds ratio (95% CI) of metabolic syndrome for the highest quartile of platelet parameters (platelet count, mean platelet volume, plateletcrit, platelet distribution width, platelet larger cell ratio) when compared to the lowest quartile were 1.32 (1.06, 1.64), 1.00 (0.81, 1.24), 1.37 (1.10, 1.71), 1.45 (1.14, 1.83), 1.11 (0.89, 1.39), respectively. Hypertension and diabetes modified the relationship between platelet distribution width and metabolic syndrome with the associations being significant in hypertensive and non-diabetic groups. The levels of platelet distribution width increased with the risk of metabolic syndrome in men but not in women.
The levels of platelet count, plateletcrit and platelet distribution width increased in older adults with metabolic syndrome, suggesting that these parameters may be useful biomarkers for further risk appraisal of metabolic syndrome in aged population.
Andrew R Dismukes, Vanessa J Meyer, Elizabeth A Shirtcliff, Katherine P Theall, Kyle C Esteves, and Stacy S Drury
The current investigation examined the association between the aging-related biomarkers dehydroepiandrosterone (DHEA) and telomere length (TL) in community-recruited African-American youth. The examination of DHEA included stress reactive, basal and diurnal sampling, in order to elucidate the underlying physiological process that may overlap with TL. One hundred and two participants completed the Trier Social Stressor Test for children (TSST-C). TL was obtained from all youth from buccal swabs on the same day as the TSST-C. Saliva samples from 83 participants were obtained over the course of two additional days to measure waking and diurnal levels of DHEA. DHEA diurnal slope was a robust predictor of TL (B=0.516, P<0.05), while other DHEA values were not significantly associated with TL. This study is one of the first studies to examine basal, diurnal and reactivity measurements of DHEA in youth. Furthermore, this is the first study, to our knowledge, to demonstrate a positive association between DHEA, a putative anti-aging hormone, and TL, an indicator of cellular aging.
Yun Hu, Na Li, Peng Jiang, Liang Cheng, Bo Ding, Xiao-Mei Liu, Ke He, Yun-Qing Zhu, Bing-li Liu, Xin Cao, Hong Zhou, and Xiao-Ming Mao
Thyroid nodules are usually accompanied by elevated thyroglobulin (Tg) level and autoimmune thyroid diseases (AITDs). However, the relationship between Tg and AITDs is not fully understood. Dysfunction of regulatory T cells (Tregs) plays an important role in the development of AITDs. We aimed to evaluate the effects of Tg on the function of Tregs in patients with thyroid nodules.
Tg levels and the functions of Tregs in peripheral blood and thyroid tissues of patients with thyroid nodules from Nanjing First Hospital were evaluated. The effects of Tg on the function of Tregs from healthy donors were also assessed in vitro. The function of Tregs was defined as an inhibitory effect of Tregs on the effector T cell (CD4+ CD25− T cell) proliferation rate.
The level of Tg in peripheral blood correlated negatively with the inhibitory function of Tregs (R = 0.398, P = 0.03), and Tregs function declined significantly in the high Tg group (Tg >77 μg/L) compared with the normal Tg group (11.4 ± 3.9% vs 27.5 ± 3.5%, P < 0.05). Compared with peripheral blood, the function of Tregs in thyroid declined significantly (P < 0.01), but the proportion of FOXP3+ Tregs in thyroid increased (P < 0.01). High concentration of Tg (100 μg/mL) inhibited the function of Tregs and downregulated FOXP3, TGF-β and IL-10 mRNA expression in Tregs in vitro.
Elevated Tg level could impair the function of Tregs, which might increase the risk of AITDs in patient with thyroid nodules.
Qing Zhu, Jianbin Su, Xueqin Wang, Mengjie Tang, Yingying Gao, and Dongmei Zhang
Graves’ disease (GD), an organ-specific autoimmune disease, is the most common cause of hyperthyroidism. Tumour necrosis factor-alpha (TNF-α) exhibits immunological and metabolic activities involved in the induction and maintenance of immune responses. We attempted to evaluate the relationship between GD and serum TNF-α and its soluble receptors (sTNFRs), soluble TNF receptor 1 and 2 (sTNF-R1 and sTNF-R2). A total of 72 GD patients and 72 matched healthy individuals were recruited for this study. Serum TNF-α and sTNFRs were measured by sandwich ELISA. In our study, no significant difference was observed in TNF-α, but sTNFRs were found to be significantly elevated in GD patients compared to healthy individuals. Serum sTNFR levels were positively correlated with free triiodothyronine (FT3) and free thyroxine (FT4), and TNF-α was negatively correlated with thyroid-stimulating hormone (TSH) in the GD group. It was also shown that thyrotropin receptor antibody (TRAb) was positively correlated with TNF-α and sTNFRs. Spearman’s correlation analysis showed that only sTNF-R1 was positively correlated with complement C3. Multiple linear regression analysis suggests that serum levels of sTNF-R1 and FT4 may play an important role in the serum level of FT3. According to the median value of FT3 level, GD patients were further divided into a high FT3 group and a low FT3 group. The serum levels of sTNF-R1 in the high FT3 GD group were significantly higher than those in the low FT3 GD group. In conclusion, sTNFRs may play an important role in anti-inflammatory and immune response in GD.
Earn H Gan, Wendy Robson, Peter Murphy, Robert Pickard, Simon Pearce, and Rachel Oldershaw
The highly plastic nature of adrenal cortex suggests the presence of adrenocortical stem cells (ACSC), but the exact in vivo identity of ACSC remains elusive. A few studies have demonstrated the differentiation of adipose or bone marrow-derived mesenchymal stem cells (MSC) into steroid-producing cells. We therefore investigated the isolation of multipotent MSC from human adrenal cortex.
Human adrenals were obtained as discarded surgical material. Single-cell suspensions from human adrenal cortex (n = 3) were cultured onto either complete growth medium (CM) or MSC growth promotion medium (MGPM) in hypoxic condition. Following ex vivo expansion, their multilineage differentiation capacity was evaluated. Phenotype markers were analysed by immunocytochemistry and flow cytometry for cell-surface antigens associated with bone marrow MSCs and adrenocortical-specific phenotype. Expression of mRNAs for pluripotency markers was assessed by q-PCR.
The formation of colony-forming unit fibroblasts comprising adherent cells with fibroblast-like morphology were observed from the monolayer cell culture, in both CM and MGPM. Cells derived from MGPM revealed differentiation towards osteogenic and adipogenic cell lineages. These cells expressed cell-surface MSC markers (CD44, CD90, CD105 and CD166) but did not express the haematopoietic, lymphocytic or HLA-DR markers. Flow cytometry demonstrated significantly higher expression of GLI1 in cell population harvested from MGPM, which were highly proliferative. They also exhibited increased expression of the pluripotency markers.
Our study demonstrates that human adrenal cortex harbours a mesenchymal stem cell-like population. Understanding the cell biology of adrenal cortex- derived MSCs will inform regenerative medicine approaches in autoimmune Addison’s disease.