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Guoying Wang, Xin Liu, Katherine Kaufer Christoffel, Shanchun Zhang, Binyan Wang, Rong Liu, Zhiping Li, Xue Liu, Wendy J Brickman, Donald Zimmerman, Xiping Xu and Xiaobin Wang

Objective

This study investigated the associations of plasma leptin levels with insulin resistance (IR) and prediabetes in relatively lean, rural Chinese men and women.

Design and methods

This study included 574 subjects aged 21–45 years from a community-based twin cohort. Plasma leptin concentrations were measured by sandwich immunoassays using flowmetric xMAP technology. Prediabetes was defined based on fasting plasma glucose and 75-g oral glucose tolerance test. Multivariate linear and logistic regression analyses were used to investigate gender-specific associations of leptin with IR measures and prediabetes, adjusting for intra-twin correlation, measures of adiposity, and other pertinent covariates.

Results

The body mass index is 22.3±2.7 kg/m2 in men and 22.5±2.7 kg/m2 in women. Leptin levels were positively associated with IR. Individuals with higher tertiles of leptin also had increased risk of prediabetes with odds ratios (OR) of 2.6 (95% confidence interval (CI): 1.4–5.1) and 4.3 (95% CI: 2.1–8.7) in men; OR of 1.1 (95% CI: 0.6–2.1) and 3.1 (95% CI 1.5–6.2) in women for second and third tertile respectively. These associations were attenuated after further adjusting for adiposity measurements only in men. The leptin–prediabetes associations disappeared after adjusting for the homeostatic model assessment of IR in both genders.

Conclusion

In this sample of relatively lean rural Chinese adults, plasma leptin levels were associated with IR and prediabetes in a dose–response fashion, which were not totally explained by adiposity. Our data emphasize that prediabetes is not all about obesity, and leptin may be an additional biomarker for screening individuals at high risk for prediabetes in this population.

Free access

Tao Liu, Wei-Qing Chen, Sean P David, Rachel F Tyndale, Hui Wang, Yu-Ming Chen, Xue-Qing Yu, Wei Chen, Qian Zhou and Wen-Hua Ling

Objective

To explore the interactions between smoking and CYP2A6 genotypes on type 2 diabetes (T2DM) as well as potential pathways for smoking in causing T2DM.

Design

Cross-sectional study.

Methods

A total of 1344 smokers with complete data from a community-based T2DM survey in Guangzhou and Zhuhai of China from July 2006 to June 2007 were interviewed with a structured questionnaire about socio-demographic status and daily cigarette consumption. Serum glucose, insulin, and cotinine were measured after an overnight fast. Subjects were genotyped for CYP2A6 and classified, according to genotype, into normal, intermediate, slow, or poor nicotine metabolizers based on prior knowledge of CYP2A6 allele associations with nicotine C-oxidation rate. Abdominal obesity was defined as a waist-to-hip ratio ≥0.90 for males or ≥0.85 for females. Type 2 diabetic patients (n=154) were diagnosed according to WHO 1999 criteria. Chi-square tests, multivariate logistic regression models, and a structural equation model were used in this study.

Results

Multivariate analysis indicated that, compared with light smoking, heavy smoking significantly increased the risk of T2DM (odds ratio (OR)=1.75, 95% CI=1.01–3.05). There were significant interactions between heavy smoking and slow CYP2A6 (OR=5.12, 95% CI=1.08–24.23) and poor CYP2A6 metabolizer genotypes (OR=8.54, 95% CI=1.28–57.02) on T2DM. Structural equation modeling indicated that CYP2A6 moderation of smoking quantity risk on T2DM was mediated by the effects on serum cotinine, abdominal obesity, insulin resistance, and insulin secretion.

Conclusions

Heavy smoking was significantly associated with T2DM, and this association was moderated by CYP2A6 genotype and mediated by serum cotinine, abdominal obesity, insulin resistance, and insulin secretion.

Restricted access

Jingjing Jiang, Xue Liu, Xiaotian Liu, Zhongyan Tian, Haiqing Zhang, Xinling Qian, Zhicheng Luo, Dandan Wei, Shuna Jin, Chongjian Wang and Zhenxing Mao

Objective

Previous studies have uncovered a progestin-only contraceptive association with an increased risk of diabetes, but limited studies have explored the relationship of endogenous progesterone and pregnenolone levels with diabetes status. A case–control study was conducted in Henan Rural Cohort (register number: ChiCTR-OOC-15006699) to evaluate the dose–response independent and interactive relationship of progesterone and pregnenolone levels with prediabetes and type 2 diabetes mellitus (T2DM) in Chinese rural population.

Design

A case-control study.

Methods

A total of 798 T2DM patients, 779 prediabetes patients, and 782 individuals with normal fasting plasma glucose were included in this study. Serum progesterone and pregnenolone were detected by liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were used to assess the independent effects of progesterone and pregnenolone on prediabetes and T2DM. Interactive plots were employed to examine the interaction effects of progesterone and pregnenolone.

Results

Progesterone in the fourth versus first quartile was positively associated with prediabetes (odds ratio (OR) (95% CI): 2.66 (1.99–3.55)) and T2DM (OR (95% CI): 6.41 (4.57–8.98)), whereas pregnenolone in the fourth versus first quartile was inversely related to prediabetes (OR (95% CI): 0.23 (0.16–0.33)) and T2DM (OR (95% CI): 0.44 (0.31–0.62)). Additionally, the nonlinear dose–response associations between progesterone and pregnenolone with prediabetes and T2DM were found. Interactive effects of progesterone and pregnenolone on prediabetes and T2DM were observed, and these significant associations remained in gender-stratified analysis.

Conclusions

Prediabetes and T2DM were positively linked to serum concentration of progesterone and negatively related to pregnenolone in a dose–response manner in Chinese rural population.

Open access

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

Background

Convincing evidence has demonstrated the association of TSH receptor (TSHR) with Graves' disease (GD) in the Chinese Han population.

Objective

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.

Results

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.

Conclusions

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.

Restricted access

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.

Methods

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.

Results

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.

Conclusions

Frequent consumption of raw garlic is inversely associated with NAFLD in Chinese men. Further investigations are needed to confirm this finding.

Free access

Weiwei Wang, Weiping Teng, Zhongyan Shan, Sen Wang, Jianxin Li, Lin Zhu, Jin Zhou, Jinyuan Mao, Xiaohui Yu, Jia Li, Yanyan Chen, Haibo Xue, Chenling Fan, Hong Wang, Hongmei Zhang, Chenyang Li, Weiwei Zhou, Bo Gao, Tao Shang, Jiaren Zhou, Bin Ding, Ying Ma, Ying Wu, Hui Xu and Wei Liu

Context

Maternal thyroid disorders during early pregnancy can influence pregnancy outcome and fetal development. The recent Endocrine Society Clinical Practice Guideline recommends a case-finding approach in which pregnant women who are at high risk for developing thyroid disease are tested.

Objective

The purpose of this study was to use the first trimester-specific reference intervals of thyroid-related hormones to explore the prevalence of thyroid dysfunction during early pregnancy and to analyze effectiveness of different screening strategies.

Design

A multicenter cohort study.

Method

A total of 2899 pregnant women were enrolled in this study during their first trimester of gestation. Levels of TSH, free thyroxine, free triiodothyronine, and thyroid peroxidase antibodies (TPOAb) were measured and thyroid disorders of pregnant women were diagnosed based on the first trimester-specific reference intervals.

Results

The prevalence of hypothyroidism was significantly higher in the high-risk group than in the non-high-risk group (10.9 vs 7.0%, χ 2=7.1, P=0.008). The prevalence of hyperthyroidism was not significantly different between the high-risk group and the non-high-risk group (2.7 vs 1.6%, χ 2=2.27, P=0.13). Elevated levels of TPOAb and a personal history of thyroid disease increased the risk of thyroid dysfunction.

Conclusions

A case-finding strategy for screening thyroid function in the high-risk group would miss about 81.6% pregnant women with hypothyroidism and 80.4% pregnant women with hyperthyroidism.