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Ke Li, Ling Li, Mengliu Yang, Hua Liu, Dongfang Liu, Hao Yang, Guenther Boden and Gangyi Yang

Objective

To investigate the effects of short-term continuous subcutaneous insulin infusion (CSII) on plasma vaspin levels in patients with newly diagnosed type 2 diabetes mellitus (T2DM).

Method

Thirty patients with severe newly diagnosed T2DM, 37 subjects with impaired glucose tolerance (IGT) and 38 gender-, age- and body mass index (BMI)-matched normal GT (NGT) controls participated in the study. The T2DM group was treated with CSII for 2 weeks. Euglycemic–hyperinsulinemic clamps were performed in 16 subjects of the T2DM group. Plasma vaspin concentrations were measured with a commercial ELISA kit. The relationship between plasma vaspin levels and metabolic parameters was also analyzed.

Results

Fasting plasma vaspin levels were higher in the T2DM group than in IGT and NGT groups (1.83±0.55 vs 0.51±0.21 vs 0.53±0.24 μg/l, P<0.05), but there was no difference between IGT and NGT groups. In T2DM patients, fasting plasma vaspin concentrations were significantly decreased after CSII treatment for 2 weeks (1.83±0.55 vs 1.19±0.57 μg/l, P<0.05), accompanied by significant amelioration of insulin sensitivity and glucose control. The changes in plasma vaspin levels were positively associated with the amelioration of insulin resistance (IR) shown by the changes in homeostasis model assessment of IR.

Conclusion

Plasma vaspin level is associated with IR and is significantly reduced following short-term CSII treatment.

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Tao Tao, Shengxian Li, Aimin Zhao, Yanyun Zhang and Wei Liu

Objective

Alterations in the phenotypes of macrophages in adipose tissue play a key role in inflammation and insulin resistance (IR). The phenotypes of macrophages in subcutaneous adipose tissue (SAT) and the relationship between proinflammation markers and IR in women with polycystic ovary syndrome (PCOS) remain unclear. The objectives of this study are to characterize the gene expression of macrophage markers and cytokines in the SAT of PCOS women and to estimate their relationships with circulating levels of cytokines and IR.

Methods

The cross-sectional study involves 16 PCOS women and 18 normal control women. Cytokines and macrophage markers in the circulation and SAT were determined using ELISA, quantitative PCR, or immunofluorescence staining. IR was estimated using the homeostasis model assessment (HOMA-IR).

Results

The gene expression levels of CD11c along with TNF α and leptin in SAT remained significantly higher in PCOS women than in normal women (P<0.05). However, no significant differences were found in CD68 mRNA expression in SAT between women with and without PCOS (P>0.05). Furthermore, CD11c mRNA abundance provided a stronger contribution to models predicting serum levels of TNFα (sTNFα) than did CD68 mRNA abundance. Lastly, increased sTNFα was associated with increased HOMA-IR in PCOS women, and this association was independent of both overall and visceral adiposity.

Conclusion

The high expression level of CD11c mRNA in SAT was proved to be an important feature in PCOS women. Furthermore, CD11c mRNA abundance made a stronger contribution to models predicting sTNFα in which existing proinflammatory properties might significantly contribute to the pathogenesis of IR in PCOS women.

Free access

Dandong Wu, Ling Li, Mengliu Yang, Hua Liu and Gangyi Yang

Objective

Secreted protein acidic and rich in cysteine (SPARC) also known as BM-40 which has been studied in various pathological conditions, has recently been suggested as a key player in the pathology of obesity and type 2 diabetes mellitus (T2DM). However, there are few studies on putative pathophysiologic roles of SPARC in glucose metabolism. The aim of this study was to determine whether plasma SPARC concentrations were altered in subjects with different glucose metabolic conditions and to investigate the affecting factors.

Design and methods

In this study, 54 newly diagnosed T2DM subjects, 53 subjects with impaired glucose regulation (IGR), and 53 normal subjects (body mass index (BMI): 24.98±3.75 vs 24.70±2.78 and 24.53±3.66 kg/m2, P>0.05) were enrolled. Plasma SPARC levels were measured with an ELISA under overnight fasting conditions. The relationships between plasma SPARC and several metabolic factors, such as BMI, blood lipids, blood glucose, plasma insulin levels, and other factors were also assessed.

Results

SPARC levels were higher in subjects with T2DM compared with IGR and control subjects (16.74±6.99 vs 14.04±8.03 μg/l, P<0.05 and 16.74±6.99 vs 11.72±4.47 μg/l, P<0.01). However, there was no difference in plasma SPARC levels between IGR subjects and the controls. Plasma SPARC levels correlated positively with BMI, the percentage of fat, triglyceride, fasting plasma insulin, 2 h plasma insulin after a glucose load, and the homeostasis model assessment of insulin resistance in simple regression analysis.

Conclusion

The present work indicates a potential link between SPARC and the pathogenesis of T2DM.

Restricted access

Yunting Lin, Yanna Cai, Jianan Xu, Chunhua Zeng, Huiying Sheng, Yang Yu, Xiuzhen Li and Li Liu

Objective: X-linked hypophosphatemic rickets (XLHR) is the most common form of inherited rickets caused by pathogenic variants of PHEX gene with an X-linked dominant inheritance pattern. Precise molecular diagnosis of pathogenic variant will benefit the genetic counseling and prenatal diagnosis for the family with XLHR. Here we presented an “isolated” germline mosaicism in the phenotypically normal father of a girl with XLHR.

Methods and Results: For the initial molecular screen of PHEX gene, DNA samples of the proband and her parents were extracted from their peripheral blood samples respectively. Sanger sequencing found a 'de novo' novel heterozygous variant, c.1666C>T(p.Q556X), at the PHEX gene in the proband, but not in her phenotypically healthy parents. Due to an occasional abnormality of his serum phosphate previously, further examinations for the father were taken to exclude the possibility of paternal mosaicism. Eight samples from different tissues were analyzed for PHEX gene by Sanger sequencing. Surprisingly, one 'isolated' germline mosaicism was detected only in his sperm with an estimated 26.67% of frequency. The mosaic allele was identical to the c.1666C>T(p.Q556X) variant in the proband.

Conclusions: This is the first case of 'isolated' germline mosaicism with pathogenic PHEX variant. Our study provides accurate diagnosis and valuable counseling for this family. This report also alerts clinicians and geneticists to exclude the possibility of the isolated germline mosaicism and prevent intrafamilial recurrences of inherited diseases.

Free access

Ke Li, Ling Li, Mengliu Yang, Haihong Zong, Hua Liu and Gangyi Yang

Objective

Fibroblast growth factor-21 (FGF-21) has recently been characterized as a potent metabolic regulator, but its pathophysiologic roles in humans remain unknown. This study aimed to investigate the effects of rosiglitazone on plasma FGF-21 levels in patients with type 2 diabetes mellitus (T2DM).

Design and methods

Thirty patients with new-onset T2DM (nT2DM), 34 type 2 diabetic patients with poor glycemic control (pT2DM) after the treatment with single hypoglycemic agent metformin, and 30 sex- and age-matched normal glycaemic controls (NGT) participated in the study. The pT2DM group was treated with rosiglitazone for 12 weeks. Plasma FGF-21 levels were measured with a RIA. The relationship between plasma FGF-21 levels and metabolic parameters was also analyzed.

Results

Fasting plasma FGF-21 levels were higher in nT2DM and pT2DM groups than in the control (1.81±0.64 vs 1.87±0.63 vs 1.52±0.61 μg/l, P<0.05), but there was no difference between nT2DM and pT2DM groups. Fasting plasma FGF-21 levels were decreased significantly in pT2DM group after the treatment with rosiglitazone compared with pre-treatment (1.59±0.63 vs 1.87±0.64 μ/l, P<0.05). In all diabetic patients, multiple regression analysis showed that HbA1c, fasting insulin, and homeostasis model assessment-insulin resistance index were independently associated with plasma FGF-21 levels.

Conclusions

In pT2DM patients, plasma FGF-21 levels are increased, but significantly decreased after the treatment with rosiglitazone on top of ongoing metformin therapy. These data suggest that rosiglitazone may play a role in lowering FGF-21 levels in T2DM patients.

Free access

Mingyuan Tian, Zerong Liang, Rui Liu, Ke Li, Xinrong Tan, Yong Luo, Mengliu Yang, Harvest F Gu, Hua Liu, Ling Li and Gangyi Yang

Objective

Zinc-α2-glycoprotein (ZAG) has recently been characterized as a potent metabolic regulator. However, the effects of anti-diabetic agents on circulating ZAG levels in humans remain largely unknown. To explore the possible mechanisms by which the dipeptidyl peptidase-IV (DPP-IV) inhibitor improves insulin resistance, we investigated the effect of sitagliptin, a DPP-IV inhibitor, on circulating cytokine levels in newly diagnosed type 2 diabetes (nT2DM) patients.

Design and methods

A subset of 141 subjects with nT2DM were assigned to receive placebo (n=47) or sitagliptin (n=94) for 3 months. Before and after treatment, subjects received a 75 g oral glucose tolerance test, euglycemic-hyperinsulinemic clamp (EHC), and measurement of ZAG and adiponectin (ADI) concentrations.

Results

Circulating ZAG levels were lower in nT2DM than in control individuals (P<0.01). After 3 months of sitagliptin treatment, HbA1c, fasting plasma glucose, postprandial glucose, 2-h insulin after glucose overload, triglycerides, and homeostasis model assessment of insulin resistance (HOMA-IR) were decreased significantly compared with pre-treatment (P<0.05 or P<0.01), whereas the glucose infusion rate during the stable period of the clamp (M values) during EHC were significantly increased (P<0.01). In addition, circulating ZAG and ADI concentrations were significantly increased along with improved glucose metabolism and insulin sensitivity compared with pre-treatment (both P<0.01) and the change of ZAG (ΔZAG) was positively associated with ΔADI, ΔHOMA-IR, ΔBMI, Δfasting insulin and negatively associated with Δ tumor necrosis factor-α (TNF-α). Furthermore, sitagliptin treatment resulted in significantly lowered plasma TNF-α level (P<0.05).

Conclusion

A low level of circulating ZAG is associated with insulin resistance and sitagliptin treatment significantly increases circulating ZAG levels. These observations have implications in relation to the mode of action of the DPP-IV inhibitor as an insulin sensitizing agent.

Free access

Peiyun Li, Zhilei Shan, Li Zhou, Manling Xie, Wei Bao, Yan Zhang, Ying Rong, Wei Yang and Liegang Liu

Objective

Epidemiologic studies regarding the association between parity and risk of type 2 diabetes have yielded inconsistent results. Therefore, we performed a systematic review and dose-response meta-analysis to determine the relation between parity and type 2 diabetes risk.

Methods

We searched PubMed and Embase for published epidemiologic studies that assessed the relation between parity and risk of type 2 diabetes up to 31 March 2016. A dose-response random-effects model was used to combine study-specific relative risks (RRs) and 95% confidence intervals (CIs). Potential sources of heterogeneity were explored by meta-regression and subgroup analyses.

Results

Seven cohort studies, 1 case-control study and 9 cross-sectional studies including 296 923 participants were eligible for inclusion. The combined RR for the highest versus lowest category of parity indicated a 54% increment in type 2 diabetes risk (95% CI: 29–83%). In the cubic spline model, a nonlinear association was found between parity and risk of type 2 diabetes (P = 0.02 for nonlinearity). Compared with nulliparous women, the estimated RR (95% CI) of type 2 diabetes for women with one to seven children was 1.01 (0.96–1.07), 1.08 (1.00–1.16), 1.20 (1.12–1.30), 1.32 (1.22–1.42), 1.37 (1.27–1.48), 1.39 (1.26–1.52) and 1.39 (1.23–1.57) respectively.

Conclusions

Higher parity is significantly associated with an increased risk of type 2 diabetes. Further studies are warranted to fully adjust for the potential confounders and explore the causality between parity and type 2 diabetes risk.

Free access

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

Xiaofei Wang, Wenli Cheng, Jingdong Li, Anping Su, Tao Wei, Feng Liu and Jingqiang Zhu

Objective

There is controversy as to whether familial nonmedullary thyroid carcinoma (FNMTC) is more aggressive than sporadic NMTC (SNMTC). The aim of the study was to evaluate the biological characteristics of patients with FNMTC by a meta-analysis.

Methods

Four databases (PubMed, EMBASE, the Cochrane library databases, and the Web of Science) were searched to identify studies published before September, 2014. All original studies that compared clinical characteristics and prognosis of patients with FNMTC and SNMTC were included. The pooled effect sizes of interesting parameters were calculated by odds ratio (OR), standard mean difference (SMD), or hazard ratio (HR).

Results

Twelve studies with a total of 12 741 participants were included in this analysis. FNMTC patients had an increased rate of recurrence (OR=1.72, 95% CI: 1.34 to 2.20) and decreased disease-free survival (DFS) (HR=1.83, 95% CI: 1.34 to 2.52) in comparison with SNMTC patients. FNMTC possessed more aggressive biological behaviors, characterized by younger age at diagnosis (SMD=−0.91, 95% CI: −1.59 to −0.22), higher risk of multifocal (OR=1.50, 95% CI: 1.32 to 1.71), bilateral (OR=1.29, 95% CI: 1.00 to 1.66), extrathyroidal invasion (OR=1.20, 95% CI: 1.02 to 1.41), and lymph node metastasis (OR=1.18, 95% CI: 1.01 to 1.38).

Conclusion

FNMTC is a more aggressive disease and possesses higher recurrence rate and lower DFS. More attention and careful consideration should be paid regarding the decision about treatment for patients with FNMTC.

Free access

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.