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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

Aim

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).

Results

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.

Conclusion

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.

Free access

Li Song, Liping Liu, R Tyler Miller, Shirley X Yan, Nancy Jackson, Shelby A Holt and Naim M Maalouf

Objective

Autoimmune lymphocytic parathyroiditis and acquired hypocalciuric hypercalcemia associated with autoantibodies against the calcium-sensing receptor (anti-CaSR) are rare and poorly understood conditions. Here, we describe a patient with acquired parathyroid hormone (PTH)-dependent hypercalcemia with associated hypocalciuria, found to have true lymphocytic parathyroiditis on histopathology, and circulating anti-CaSR antibodies in serum.

Design and methods

A 64-year-old woman was referred to our clinic for persistent hypercalcemia after a subtotal parathyroidectomy. She was normocalcemic until the age of 63 years when she was diagnosed with primary hyperparathyroidism. She underwent subtotal parathyroidectomy with appropriate intraoperative PTH decline. Two weeks post-parathyroidectomy, she presented with persistent hypercalcemia and hyperparathyroidism. Urine studies revealed an inappropriately low 24-h urine calcium (Ca)/creatinine clearance ratio. Surgical pathology was consistent with true lymphocytic parathyroiditis with lymphoid follicles. The presence of circulating anti-CaSR antibodies was detected by immunoprecipitation of CaSR by the patient’s serum. After a 4-week course of prednisone, serum Ca and PTH normalized, and her anti-CaSR titers declined. She remains normocalcemic 10 months after the discontinuation of glucocorticoid therapy. We present this patient in the context of the relevant published literature on lymphocytic parathyroiditis and acquired hypocalciuric hypercalcemia related to anti-CaSR antibodies.

Conclusions

Autoimmune lymphocytic parathyroiditis and acquired hypocalciuric hypercalcemia associated with anti-CaSR antibodies is a very rare yet important condition to be considered in a patient with acquired PTH-dependent hypercalcemia with inappropriate hypocalciuria. Although subtotal parathyroidectomy is unlikely to correct the hypercalcemia, this entity may respond to a short course of prednisone therapy.

Free access

Yujin Zhang, Hongwei Liu, Jin He, Kelei Xu, Huai Bai, Ying Wang, Feng Zhang, Jinxia Zhang, Li Cheng and Ping Fan

Objective

To study the relationship between the lactonase activities and status of paraoxonase 1 (PON1) and its association with the PON1 genetic polymorphisms in women with polycystic ovarian syndrome (PCOS).

Design

A case–control study.

Methods

A total of 455 PCOS patients and 441 control women were included in this study. The lactonase activities and concentrations of PON1 were assayed using 5-thiobutyl butyrolactone (TBBL) and 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase:DEPCyMCase activity. The PON1 genotypes, serum malondialdehyde (MDA) levels and total antioxidant capacity were analyzed.

Results

The lactonase activities and levels of PON1 were higher in PCOS patients than in the control women. However, the NLA did not significantly differ between groups. The −108C T variation of the PON1 gene showed decreased lactonase activities and levels of PON1 in a genotype-dependent manner (CC>CT>TT); the 192Q R variation of the PON1 gene showed increased PON1 lactonase activities and NLA; and the 55L M variation of the PON1 gene showed decreased lactonase activities and levels of PON1 but an increased NLA. A multivariable regression analysis showed that the −108C/T, 192Q / R, and 55L/M variations of the PON1 gene, serum apolipoprotein A1, and MDA levels were significant predictors of PON1 lactonase activity, PON1 level, and NLA.

Conclusions

The serum lactonase activities and concentrations of PON1 are increased in PCOS patients. The increased oxidative stress and the −108C/T, 192Q/R, and 55L/M genetic polymorphisms of PON1 may be associated with these changes.

Free access

Yanyun Hu, Fang Liu, Jing Shen, Hui Zeng, Lianxi Li, Jun Zhao, Jungong Zhao, Fengdi Lu and Weiping Jia

Objective

Serum cystatin C (CysC) is a sensitive marker of kidney function and recent studies have shown that CysC plays a critical role in degenerative diseases in both the central and the peripheral nervous systems. The aim of this study was to explore the relationship between serum CysC and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes.

Methods

In total, 937 type 2 diabetic patients were enrolled in this cross-sectional study. Serum CysC concentration was measured by immunoturbidimetry. DPN was evaluated by neurological symptoms, neurological signs, neurothesiometer, and electromyogram.

Results

Serum CysC levels were significantly higher in DPN patients (1.3 (1.1–1.5) mg/l) compared with patients with signs of DPN (1.1 (0.9–1.3) mg/l, P<0.001) and non-DPN patients (1.0 (0.9–1.3) mg/l, P<0.001). Multiple regression analysis revealed that DPN was associated with age, diabetes duration, HbA1c, and serum CysC. Spearman's correlation analysis showed that serum CysC was closely related with age, sex, diabetes duration, hypertension, glomerular infiltration rate, and serum creatinine (Cr) level. The patients were divided into quartiles according to the serum CysC levels. Compared with quartile 1 (referent), the risk of DPN was significantly higher in quartile 2 (odds ratio (OR), 1.753; 95% CI, 1.055–2.912; P<0.05), quartile 3 (OR, 2.463; 95% CI, 1.445–4.917; P<0.01), and quartile 4 (OR, 5.867; 95% CI, 2.075–16.589; P<0.01). Receiver-operating characteristic analysis revealed that the optimal cutoff point of serum CysC to indicate DPN was 1.25 mg/l in male patients and 1.05 mg/l in female patients. High serum CysC level indicated a onefold higher risk of DPN.

Conclusions

High serum CysC level is closely associated with DPN and may be a potential biomarker for DPN in type 2 diabetic patients.

Free access

Yun Shen, Peng Wang, Leishen Wang, Shuang Zhang, Huikun Liu, Weiqin Li, Nan Li, Wei Li, Junhong Leng, Jing Wang, Huiguang Tian, Cuilin Zhang, Jaakko Tuomilehto, Xilin Yang, Zhijie Yu and Gang Hu

Aims

To compare risks of early postpartum diabetes and prediabetes in Chinese women with and without gestational diabetes mellitus (GDM) during pregnancy.

Subjects and methods

Tianjin GDM observational study included 1263 women with a history of GDM and 705 women without GDM who participated in the urban GDM universal screening survey by using World Health Organization’s criteria. Postpartum diabetes and prediabetes were identified after a standard oral glucose tolerance test. Cox proportional hazards regression was used to assess risks of postpartum diabetes and prediabetes between women with and without GDM.

Results

During a mean follow-up of 3.53 years postpartum, 90 incident cases of diabetes and 599 incident cases of prediabetes were identified. Multivariable-adjusted hazard ratios among women with prior GDM, compared with those without it, were 76.1 (95% CI: 23.6–246) for diabetes and 25.4 (95% CI: 18.2–35.3) for prediabetes. When the mean follow-up extended to 4.40 years, 121 diabetes and 616 prediabetes cases were identified. Women with prior GDM had a 13.0-fold multivariable-adjusted risk (95% CI: 5.54-30.6) for diabetes and 2.15-fold risk (95% CI: 1.76-2.62) for prediabetes compared with women without GDM. The positive associations between GDM and the risks of postpartum diabetes and prediabetes were significant and persistent when stratified by younger and older than 30 years at delivery and normal weight and overweight participants.

Conclusions

The present study indicated that women with prior GDM had significantly increased risks for postpartum diabetes and prediabetes, with the highest risk at the first 3–4 years after delivery, compared with those without GDM.

Free access

Junhong Leng, Gongshu Liu, Cuiping Zhang, Shijuan Xin, Fang Chen, Baojuan Li, Huiguang Tian, Zhijie Yu, Jaakko Tuomilehto, Gang Hu and Xilin Yang

Objective

Physical activity in a nonpregnant state or before pregnancy reduces the risk of type 2 diabetes and is also associated with reduced risk of gestational diabetes mellitus (GDM). However, it is uncertain whether physical activity during pregnancy reduces the risk of GDM.

Design and methods

Using an established universal screening system in Tianjin, China, we prospectively recruited 11 450 pregnant women within the 12th gestational week from 2010 to 2012. These women underwent a 50-g 1-h glucose challenge test (GCT) at 24–28 weeks of gestation and a 75-g 2-h oral glucose tolerance test if GCT glucose ≥7.8mmol/L. GDM was defined according to the International Association of Diabetes and Pregnancy Study Group’s criteria. Self-reported physical activity in the last month was collected at GCT time using a validated questionnaire.

Results

GDM developed in 7.3% (n=840) of the women. Women with GDM were less likely to be engaged in moderate-to-high physical activity during pregnancy than those without (79.8% vs 81.6%, P=0.191). Moderate-to-high physical activity during pregnancy was associated with decreased risk of GDM (multivariable odds ratio (OR): 0.81, 95% confidence interval (CI): 0.67–0.97). Sitting at home for 2–4h per day and >4h per day were associated with significantly increased risk of GDM (multivariable OR of sitting time for 2–4h vs <2h: 1.59, 95% CI: 1.18–2.15; OR of sitting time for >4h vs <2h: 1.73, 95% CI: 1.22–2.43).

Conclusions

Increased physical activity during pregnancy was associated with reduced GDM risk, whereas sedentary lifestyle was associated with increased GDM risk among Chinese pregnant women.

Free access

Qibin Qi, Jing Wang, Huaixing Li, Zhijie Yu, Xingwang Ye, Frank B Hu, Oscar H Franco, An Pan, Yong Liu and Xu Lin

Objective

Resistin increases insulin resistance (IR) in mice. However, the role of resistin in human disease remains controversial. We aimed to assess plasma resistin levels and their associations with inflammatory and fibrinolytic markers, IR and metabolic syndrome (MetS) among Chinese.

Design and methods

Plasma resistin was measured in a population-based cross-sectional survey of 3193 Chinese aged from 50 to 70 years in Beijing and Shanghai.

Results

The median resistin concentration was 8.60 ng/ml (interquartile range, 5.78–14.00) among all participants, and it was higher in women than in men (P=0.008). Resistin was correlated weakly with body mass index, waist circumference, high-density lipoprotein (HDL) cholesterol (negatively), homeostatic model assessment of IR and tumor necrosis factor-α receptor 2 (TNFR2; r=0.04, 0.07, –0.09 and 0.06 respectively, all P<0.05), and more highly with C-reactive protein (CRP), interleukin (IL)6 and plasminogen activator inhibitor (PAI)1 (r=0.12, 0.12 and 0.21 respectively, all P<0.001), but only HDL cholesterol, CRP, IL6, TNFR2, and PAI1 remained significantly associated with resistin in multiple regression analysis (all P<0.05). Furthermore, elevated resistin levels were associated with the higher prevalence of IR and MetS. However, the significant relationships disappeared after adjustment for inflammatory and fibrinolytic markers especially PAI1.

Conclusions

This study suggests that resistin is more strongly associated with inflammatory and fibrinolytic markers than with obesity or IR status. The associations of resistin with IR and MetS could largely be explained by inflammatory and fibrinolytic markers especially PAI1 levels.

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.

Open access

Zhaoyun Zhang, Qin Li, Wenqiang He, Huijia Qiu, Hongying Ye, Yongfei Wang, Ming Shen, Min He, Yifei Yu, Xuefei Shou, Chuanxin Huang, Huan Yu, Guoqian Huang, Weijun Tang, Daoying Geng, Chaowei Fu, Congjin Liu, Zengyi Ma, Zhao Ye, Qilin Zhang, Yichao Zhang, Yue Shen, Yeping Yang, Meng Wang, Xingdang Liu, Yun Lu, Renming Hu, Ying Mao, Liangfu Zhou, Yiming Li, Shiqi Li, Nicholas A Tritos and Yao Zhao

Context

Chronic excess of growth hormone (GH) often leads to systemic complications. The reversibility of these complications after GH resolution is not fully understood.

Objective

To investigate when and to what extent will the comorbidities be ameliorated.

Design

We conducted a prospective study comprising 24 patients with acromegaly, who achieved remission after transsphenoidal surgery. The dynamic changes of endocrine, cardiovascular, respiratory, sleep, bone and morphology parameters were evaluated at enrollment and 1 week, 1 month, 3 months, 6 months and 12 months after surgery.

Results

Random GH dropped by 98.4% at the first day postoperatively. IGF-I index dropped by 50% and 64% at 1 week and 1 month respectively and remained unchanged onwards. Glucose metabolism improved significantly at 1 week and stabilized at 1 month. Testosterone in male patients recovered to normal range since 1 month. Systolic blood pressures dropped markedly at 3 months while diastolic blood pressures fell mildly at later visits. Abnormal lung function showed no improvement. The decrease of bone formation and resorption markers occurred at 1 week and 3 months, respectively. At 1 month, the tongue area declined while the airway volume increased significantly, accompanied with improved obstructive sleep apnea syndrome. Extremities, lips and nasal ala became smaller since 1 week. Liver, kidney and spleen volumes declined by 6.4, 15.9, 9.2%, respectively at 1 month. The volumes of pancreas and adrenal showed no change.

Conclusions

The rapid resolution of excessive GH led to the reversible changes of systemic comorbidities in a time-dependent and organ-specific manner.

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.