Hongbo Yang, Kemin Yan, Xu Yuping, Qi Zhang, Linjie Wang, Fengying Gong, Huijuan Zhu, Weibo Xia and Hui Pan
Adult growth hormone deficiency (AGHD) is characterized by low bone density and increased risk of fracture. Bone microarchitecture is insufficiently evaluated in patients with childhood-onset AGHD (CO AGHD).
To assess volumetric bone density (vBMD) and bone microarchitecture in CO AGHD in early adulthood after cessation of recombinant growth hormone (rhGH) treatment.
Design and subjects
Case–control study in a major academic medical center in Beijing, including 20 young male adults with CO AGHD and 30 age- and weight-matched non-athletic healthy men. High-resolution peripheral quantitative computerized tomography (HR-pQCT) of distal radius and tibia was performed.
The main outcomes were vBMD and morphometry parameters from HR-pQCT.
Compared with healthy controls, CO AGHD group had significantly decreased insulin-like growth factor 1 (IGF-1) level and IGF-1 SDS (P < 0.001). β-CTX and alkaline phosphatase levels in CO AGHD group were significantly increased (P < 0.001). CO AGHD group had significantly decreased total vBMD, cortical vBMD, trabecular vBMD, cortical area, cortical thickness as well as trabecular thickness and trabecular bone volume fraction of both tibia and radius (P < 0.001). CO AGHD patients had an 8.4 kg decrease in grip strength and a significant decrease in creatinine levels (P = 0.001). At both tibia and radius, by finite element analysis, bone stiffness and failure load of the CO AGHD patients were significantly decreased (P < 0.001). After adjusting for age, BMI and serum levels of testosterone and free thyroxin, serum IGF-1 level was a positive predictor for total vBMD, cortical vBMD, cortical area, trabecular vBMD, bone stiffness and failure load of both tibia and distal radius in all subjects.
Young adult male patients with childhood-onset adult growth hormone deficiency who are no longer receiving growth hormone replacement have prominently impaired volumetric bone density and bone microarchitecture and lower estimated bone strength.
Xiaoyan Guo, Shu Zhang, Qing Zhang, Li Liu, Hongmei Wu, Huanmin Du, Hongbin Shi, Chongjin Wang, Yang Xia, Xing Liu, Chunlei Li, Shaomei Sun, Xing Wang, Ming Zhou, Guowei Huang, Qiyu Jia, Honglin Zhao, Kun Song and Kaijun Niu
It is widely known that inflammation is related to type 2 diabetes (T2D), but few studies have shown a direct relationship between the immune system and T2D using a reliable biomarker. Neutrophil:lymphocyte ratio (NLR) is an easy-to-analyze inflammation biomarker, but few studies have assessed the relationship between NLR and T2D. In order to evaluate how NLR is related to T2D, we designed a large-scale cross-sectional and prospective cohort study in an adult population.
Subjects and methods
Participants were recruited from the Tianjin Medical University General Hospital-Health Management Centre. Both a baseline cross-sectional (n=87 686) and a prospective (n=38 074) assessment were performed. Participants without a history of T2D were followed up for ∼6 years (with a median follow-up of 2.7 years). Adjusted logistic and Cox proportional hazards regression models were used to assess relationships between the quintiles of NLR and T2D (covariates: age, sex, BMI, smoking status, drinking status, hypertension, hyperlipidemia, and family history of cardiovascular disease, hypertension, hyperlipidemia, or diabetes).
The prevalence and incidence of T2D were 4.9% and 6.8/1000 person-years respectively. The adjusted odds ratio and hazard ratio (95% CI) of the highest NLR quintile were 1.34 (1.21, 1.49) and 1.39 (1.09, 1.78) (both P for trend <0.01) respectively as compared to the lowest quintile of NLR. Leukocyte, neutrophil, and lymphocyte counts do not significantly predict the eventual development of T2D.
The present study demonstrates that NLR is related to the prevalence and incidence of T2D, and it suggests that NLR may be an efficient and accurate prognostic biomarker for T2D.
Bing-Li Liu, Shao-Ying Yang, Wei Liu, Li-Qiong Xue, Xia Chen, Chun-Ming Pan, Zhao-Hui Gu, Ming Zhan, Xiao-Mei Zhang, Jun Liang, Guan-Qi Gao, Wen-Hua Du, Guo-Yue Yuan, Ru Ying, Shuang-Xia Zhao and Huai-Dong Song
Convincing evidence has demonstrated the association of TSH receptor (TSHR) with Graves' disease (GD) in the Chinese Han population.
The aim of this study was to identify the causal variants for GD in the region encompassing TSHR by a refining association study.
Design and methods
GD patients (1536) and 1516 sex-matched controls were recruited in the first stage, and an additional 3832 GD patients and 3426 sex-matched controls were recruited in the replication stage. Genotyping was performed using Illumina Human660-Quad BeadChips or TaqMan single nucleotide polymorphism (SNP) Genotyping Assays and the Fluidigm EP1 platform.
When the results of regression analysis for 74 genotyped SNPs and 922 imputed SNPs in the first-stage cohort were combined, rs179243 and rs3783949 were the probable susceptibility SNPs associated with GD in TSHR. Eleven SNPs, including rs179243 and rs3783949, were selected to further refine the association in the replication study. Finally, rs12101261 and rs179243 were confirmed as independent GD susceptibility variants in the replication and combined populations. Further, we also found that the rate of persistent TSHR autoantibody positivity (pTRAb+) was significantly higher in the GD patients with the susceptible genotypes rs12101261 or rs179243 than in the GD patients carrying the protective genotypes, after the GD patients had been treated for more than 1 year.
These findings indicate that rs12101261 and rs179243 are the possible causal SNPs for GD susceptibility in the TSHR gene and could serve as genetic markers to predict the outcome of pTRAb+ in GD patients.
Feng Sun, Jun-Xiu Zhang, Chang-Yi Yang, Guan-Qi Gao, Wen-Bin Zhu, Bing Han, Le-Le Zhang, Yue-Yue Wan, Xiao-Ping Ye, Yu-Ru Ma, Man-Man Zhang, Liu Yang, Qian-Yue Zhang, Wei Liu, Cui-Cui Guo, Gang Chen, Shuang-Xia Zhao, Ke-Yi Song and Huai-Dong Song
Congenital hypothyroidism (CH), the most common neonatal metabolic disorder, is characterized by impaired neurodevelopment. Although several candidate genes have been associated with CH, comprehensive screening of causative genes has been limited.
Design and methods
One hundred ten patients with primary CH were recruited in this study. All exons and exon–intron boundaries of 21 candidate genes for CH were analyzed by next-generation sequencing. And the inheritance pattern of causative genes was analyzed by the study of family pedigrees.
Our results showed that 57 patients (51.82%) carried biallelic mutations (containing compound heterozygous mutations and homozygous mutations) in six genes (DUOX2, DUOXA2, DUOXA1, TG, TPO and TSHR) involved in thyroid hormone synthesis. Autosomal recessive inheritance of CH caused by mutations in DUOX2, DUOXA2, TG and TPO was confirmed by analysis of 22 family pedigrees. Notably, eight mutations in four genes (FOXE1, NKX2-1, PAX8 and HHEX) that lead to thyroid dysgenesis were identified in eight probands. These mutations were heterozygous in all cases and hypothyroidism was not observed in parents of these probands.
Most cases of congenital hypothyroidism in China were caused by thyroid dyshormonogenesis rather than thyroid dysgenesis. This study identified previously reported causative genes for 57/110 Chinese patients and revealed DUOX2 was the most frequently mutated gene in these patients. Our study expanded the mutation spectrum of CH in Chinese patients, which was significantly different from Western countries.
Shunming Zhang, Yeqing Gu, Liu Wang, Qing Zhang, Li Liu, Min Lu, Ge Meng, Zhanxin Yao, Hongmei Wu, Yang Xia, Xue Bao, Honglei Wang, Hongbin Shi, Shaomei Sun, Xing Wang, Ming Zhou, Qiyu Jia, Kun Song, Huiling Xiang and Kaijun Niu
Background and Aims
The protective effect of garlic against nonalcoholic fatty liver disease (NAFLD) has been reported in animal studies. However, in humans, the association between garlic consumption and NAFLD is unclear. The study sought to explore the association between habitual raw garlic intake and newly diagnosed NAFLD among Chinese adults.
We performed a study of 11,326 men and 12,780 women aged 20–90 years. Habitual food intake was assessed using a validated and standardized 100-item food frequency questionnaire. Diagnosis of NAFLD was based on the liver ultrasonography and self-reported alcohol intake. Multiple logistic regression was used to evaluate the association of raw garlic intake with newly diagnosed NAFLD.
The prevalence of newly diagnosed NAFLD was 28.9% in men and 10.1% in women, respectively. In men, the fully adjusted odds ratios (95% confidence interval) of having NAFLD across increasing frequency of raw garlic intake were 1.00 (reference) for <1 time/week, 0.81 (0.73, 0.90) for 1–3 times/week, 0.66 (0.54, 0.80) for 4–6 times/week, and 0.71 (0.55, 0.90) for ≥7 times/week (P for trend <0.0001). The odds ratio for NAFLD associated with each 1 g of raw garlic/1000 kcal was 0.93 (0.90, 0.97) in men. In women, no significant association between raw garlic intake and NAFLD was identified. These associations between raw garlic intake and NAFLD were consistent in several sensitivity analyses.
Frequent consumption of raw garlic is inversely associated with NAFLD in Chinese men. Further investigations are needed to confirm this finding.