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Articles by W. Jia
Total Records ( 7 ) for W. Jia
  C. Hu , W. Jia , R. Zhang , C. Wang , J. Lu , H. Wu , Q. Fang , X. Ma and K. Xiang
 

Abstract

Aims  Retinol binding protein 4 (RBP4) is a newly discovered adipokine, which plays a role in insulin resistance and obesity. The aim of this study was to determine the relationship between genetic variants of the RBP4 gene, circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism in the Chinese population.

Methods  We sequenced exons and the putative promoter region to identify single nucleotide polymorphisms (SNPs) in the RBP4 gene in 32 Chinese subjects. Additional SNPs were selected from a public database to increase marker density. Taking account of the pairwise linkage disequilibrium and minor allele frequencies, a subset of SNPs was further genotyped in 255 Type 2 diabetic patients and 372 normal control subjects. Circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism were measured.

Results  Ten SNPs were identified and five were further genotyped in the full sample. No individual SNP was significantly associated with Type 2 diabetes, but a rare haplotype CAA formed by +5388 C>T, +8201 T>A and +8204 T>A was more frequent in diabetic patients (P = 0.0343, empirical P = 0.0659 on 10 000 permutations). In both groups, non-coding SNPs were associated with circulating RBP4 concentrations (P < 0.05). In the normal control subjects, the SNP +5388 C>T was associated with serum C-peptide levels both fasting and 2 h after an oral glucose tolerance test (P = 0.0162 and P = 0.0075, respectively).

Conclusion  Our findings suggest that genetic variants in the RBP4 gene may be associated with circulating RBP4 concentration and phenotypes related to glucose metabolism.

  D. Li , X. Hou , X. Ma , W. Zong , X. Shao , H. Lu , K. Xiang and W. Jia
  Aims  The overwhelming majority of subjects with normal glucose regulation have the highest plasma glucose concentration at 30 minutes during oral glucose tolerance. We aimed to examine the association between increment of 30-min post-challenge glucose and albuminuria in participants with normal glucose regulation.

Methods  A population-based cross-sectional study was conducted in six communities in Shanghai between 2007 and 2008. A total of 3508 subjects with normal glucose regulation had complete data and were enrolled into the analysis. Among the selected subjects, only 1525 individuals (581 men, 944 women) were examined for their serum insulin levels. We assessed post-challenge blood glucose and insulin at 0, 30 and 120 min, urinary albumin and creatinine. The 30-min post-challenge glucose increment (Δ) was calculated as 30-min post-challenge glucose minus fasting plasma glucose, and albumin/creatinine ratio was used to reflect urinary albumin excretion.

Results  Multivariable logistic regression analysis revealed that the Δ30-min post-challenge glucose was independently associated with increased albumin/creatinine ratio in men with normal glucose regulation (OR = 1.08, = 0.025), but not in women. Furthermore, multivariable linear regression analysis revealed that early-phase glucose disposition index was the main factor responsible for Δ30-min post-challenge glucose and explained 14-20% of the variance of Δ30-min post-challenge glucose in the two subgroups (< 0.05). Notably, men had higher Δ30-min post-challenge glucose and lower early-phase glucose disposition index than women (all P < 0.001).

Conclusions  The 30-min post-challenge plasma glucose increment is associated with urine albumin excretion in men with normal glucose regulation.

  C. Pan , W. Yang , W. Jia , J. Weng , G. Liu , B. Luo , X. Li , Z. Fu and H. Tian
  Aim  To describe the status of glycaemic control, self-reported adherence to treatments, psychological well-being and quality of life in Chinese patients with Type 2 diabetes in 2006.

Methods  Subjects having registered for care for > 12 months at a diabetes clinic were enrolled in this study. Glycaemic control was determined by HbA1c and plasma glucose levels; information about self-reported adherence to treatments was obtained by questionnaire; psychological well-being was assessed by use of a modified World Health Organization-5 Well-being Index; and quality of life was measured by use of a modified Diabetes Attitudes, Wishes and Needs (DAWN) survey. All data were tabulated and statistical analyses were performed.

Results  A total of 2702 patients were enrolled during 2006. Only 23% of patients achieved an HbA1c level of < 48 mmol/mol (6.5%) as per the 2007 China guideline for Type 2 diabetes and only 16.2% followed all treatment recommendations from healthcare providers. Of the patients, 46.0-68.6% of the patients showed positive psychological well-being. A quality-of-life survey showed that 28.5-50.6% of the patients experienced various diabetes-related emotional problems. Large percentages (approximately 50%) of patients were experiencing psychological insulin resistance.

Conclusions  Although in China therapies for Type 2 diabetes are more effective and available than ever before, the patient outcomes remain disappointing. Problems with glycaemic control, self-reported adherence to treatments, psychological well-being and quality of life, all of which are key to diabetes control, are common among Chinese patients with Type 2 diabetes.

  Q. Fang , S. Chen , Y. Wang , S. Jiang , R. Zhang , C. Hu , C. Wang , F. Liu , K. Xiang and W. Jia
  Aims  Hepatocyte nuclear factor-1α (HNF-1α) regulates the expression of genes encoding proteins involved in glucose metabolism and insulin secretion. Mutations in the HNF-1α gene cause maturity-onset diabetes of the young Type 3. However, the mechanism leading to this disease has not been completely ascertained. Previously, we found a novel mutation in the regulatory element of the human HNF-1α gene in two Chinese diabetes pedigrees. The nucleotide at position -128 T was substituted by G (nt-128 T[RIGHTWARDS ARROW]G). In this study, we analysed the functional defect of nt-128 T[RIGHTWARDS ARROW]G in HNF-1α transcription activity.

Methods  Luciferase reporter gene assays were carried out to examine the functional characteristics of this mutant. Electrophoretic mobility shift assays and chromatin immunoprecipitation were performed to confirm the binding of nuclear proteins to oligonucleotides.

Results  The variant construct (nt-128 T[RIGHTWARDS ARROW]G) had a 1.65-fold increase in promoter activity compared with that of the wild-type construct in HepG2 cells and a 1.33-fold increase in MIN6 cells, respectively. The variant resided at a FOXA/HNF-3 binding site identified by a series of competitive electrophoretic mobility shift assays and antibody supershift analyses. The assays showed a differential binding affinity in the wild-type and the nt-128 T[RIGHTWARDS ARROW]G mutant fragments by FOXA/HNF-3. Chromatin immunoprecipitation indicated that FOXA/HNF-3 bound to this region in vivo. One nucleotide substitution in the FOXA/HNF-3 site in the human HNF-1α regulatory element caused an increase of HNF-1α transcriptional activity.

Conclusions  Our data suggested that this substitution in the promoter region affects DNA-protein interaction and HNF-1α gene transcription. The mutant may contribute to the development of diabetes in these two nt-128 T[RIGHTWARDS ARROW]G pedigrees of Chinese.

  R. Zhang , F. Jiang , C. Hu , W. Yu , J. Wang , C. Wang , X. Ma , S. Tang , Y. Bao , K. Xiang and W. Jia
  Aims  Metabolic disorders are independent risk factors for the development of Type 2 diabetes. The aim of the study is to test the association of LPIN1 variants with Type 2 diabetes and clinical characteristics in large samples of the Chinese population.

Methods  In the first stage, 15 single nucleotide polymorphisms within the LPIN1 region were selected and genotyped in 3700 Chinese Han participants. In the second stage, the single nucleotide polymorphisms showing significant association or trends towards association were genotyped in an additional 3122 samples for replication. Meta-analyses and genotype-phenotype association studies were performed after combining the data from the two stages.

Results  In the first stage, we detected that rs16857876 was significantly associated with Type 2 diabetes with an odds ratio of 0.806 (95% CI 0.677-0.958, P = 0.015), while rs11695610 showed a trend with Type 2 diabetes (odds ratio 0.846, 95% CI 0.709-1.009, P = 0.062). In the second stage, a similar effect of rs11695610 on Type 2 diabetes was observed (odds ratio 0.849, 95% CI 0.700-1.030, P = 0.096). The meta-analyses combining the information from the two stages showed a significant effect of rs11695610 on Type 2 diabetes with an odds ratio of 0.847 (95% CI 0.744-0.965, P = 0.012). Finally, the phenotype-genotype association analyses showed that rs11695610 was associated with 2-h plasma glucose (P = 0.040) and triglyceride levels (P = 0.034).

Conclusions  Our data implied that common single nucleotide polymorphisms within the LPIN1 region were associated with Type 2 diabetes and metabolic traits in the Chinese population.

  W. Yu , F. Zhang , W. Hu , R. Zhang , C. Wang , J. Lu , F. Jiang , S. Tang , D. Peng , M. Chen , Y. Bao , K. Xiang , C. Hu and W. Jia
 

Aim

There is a close link between electrocardiographic ventricular repolarization QT parameters and Type 2 diabetes. The aim of the present study was to assess the effects of QT-related and diabetes-related variants in KCNQ1 on QT interval in a Chinese population.

Methods

We recruited 2415 patients with Type 2 diabetes and 1163 subjects with normal glucose regulation in the present study. QT interval was obtained and the heart rate-corrected QT interval (QTc) was calculated using Bazett's formula. Four single nucleotide polymorphisms in KCNQ1 were selected (rs12296050, rs12576239, rs2237892 and rs2237895) and genotyped.

Results

 In participants with normal glucose regulation, the minor allele T of rs12296050 was associated with a 3.46-ms QTc prolongation under an additive model (P = 0.0109, empirical P = 0.0498). In patients with Type 2 diabetes, we did not find any association for the single nucleotide polymorphisms.

Conclusions

Our findings indicate that KCNQ1 is associated with QT interval in a Chinese population with normal glucose regulation.

  H Li , Y Bao , A Xu , X Pan , J Lu , H Wu , H Lu , K Xiang and W. Jia
 

Objective: Fibroblast growth factor (FGF) 21, a hormone primarily secreted by liver, has recently been shown to have beneficial effects on glucose and lipid metabolism and insulin sensitivity in animal models. This study investigated the association of serum FGF21 levels with insulin secretion and sensitivity, as well as circulating parameters of lipid metabolism and hepatic enzymes in Chinese subjects.

Design: Serum FGF21 levels were determined by ELISA in 134 normal glucose tolerance (NGT), 101 isolated-impaired fasting glucose, and 118 isolated-impaired glucose tolerance (I-IGT) Chinese subjects, and their association with parameters of adiposity, glucose, and lipid profiles, and levels of liver injury markers was studied. In a subgroup of this study, the hyperglycemic clamp technique was performed in 31 NGT, 17 isolated-impaired fasting glucose, and 15 I-IGT subjects to measure insulin secretion and sensitivity to test the associations with serum FGF21.

Results: The serum FGF21 levels in I-IGT were significantly higher than NGT subjects [164.6 pg/ml (89.7, 261.0) vs. 111.8 pg/ml (58.0, 198.9); P < 0.05], and correlated positively with several parameters of adiposity. Multiple stepwise regression analysis showed an independent association of serum FGF21 with serum triglycerides, total cholesterol, and -glutamyltransferase (all P < 0.05). However, FGF21 did not correlate with insulin secretion and sensitivity, as measured by hyperglycemic clamp and a 75-g oral glucose tolerance test.

Conclusions: Serum levels of FGF21 are closely related to adiposity, lipid metabolism, and biomarkers of liver injury but not insulin secretion and sensitivity in humans.

 
 
 
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