[show abstract][hide abstract] ABSTRACT: Genome-wide association studies for type 2 diabetes mellitus (T2DM) identified FTO gene as a locus conferring increased risk for common obesity in many populations with European ancestry. However, the involvement of FTO gene in obesity or T2DM related metabolic traits has not been consistently established in Chinese populations. The objective of this study was to investigate the association of FTO genetic polymorphisms with metabolic syndrome (MetS) in Han Chinese.
We tested 41 FTO single nucleotide polymorphisms (SNPs) for association between FTO and MetS-related traits. There were a total of 236 unrelated subjects (108 cases and 128 controls), grouped according to the International Diabetes Federation (IDF) criteria.
Of the 41 SNPs examined, only SNP rs8047395 exhibited statistical significance (P = 0.026) under a recessive model, after Bonferroni adjustment for multiple testing (OR 1.64, 95%CI 1.11-2.42; P = 0.014). The common distributions of this polymorphism among Chinese--with a minor allele frequency (MAF) of 36% in the control group versus 48% in the MetS group--greatly improved our test power in a relatively small sample size for an association study. Previously identified obesity- (or T2DM-) associated FTO SNPs were less common in Han Chinese and were not associated with MetS in this study. No significant associations were found between our FTO SNPs and any endophenotypes of MetS.
A more common risk-conferring variant of FTO for MetS was identified in Han Chinese. Our study substantiated that genetic variations in FTO locus are involved in the pathogenesis of MetS.
Chinese medical journal 07/2010; 123(14):1852-8. · 0.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the influence of short-term high-fat diet (HFD) on glucose and lipid metabolism in male Han Chinese with type 2 diabetes mellitus (T2DM).
Middle-aged T2DM men supported with solely diet or diet and metformin were enrolled into the study. The design was an unblinded crossover design. Each of the subjects randomly received one from two types of isocalorie (8786.4 kJ/d) standard diet for three consecutive days on two occasions, with a 6-week wash-out period in between. The component ratios of fat, carbohydrate, and protein were 50%, 35%, and 15% vs. 25%, 60%, and 15% in patients administered with HFD or high carbohydrate diet (HCD). The 24-hour blood samples during the third day were collected. On the morning of the forth day an intravenous glucose tolerance test (IVGTT) was conducted with 25g of glucose.
According to the determination results of 24-hour profile samples, HFD resulted in a markedly increased circulating level of non-esterified fatty acid (NEFA) as compared to HCD (P < 0.001). Nearly significant higher (P = 0.056) FPG was observed 72 hours after the administration of HFD. Circulating insulin levels were comparable between the two diets. A significantly higher HDL-C was also observed after HFD administration (P < 0.05). As assessed by the IVGTT, acute insulin response of glucose (AIRg) tended to increase after the HFD administration (P = 0.06). Fasting plasma glucagons (GLG) level and AUC(Glucagon) during breakfast period (8:00-12:00) were significantly higher after HFD administration than that of after HCD administration.
Short-term HFD induced the increase of NEFA with lower glucose exposure to the patietns. Fasting plasma glucose increased at the fourth day without remarkable changes of insulin levels which may be due to the increase of hepatic glucose output after HFD administration. The short-term HFD in our study induced early stage of insulin resistance. GLG seemed to play a role in this procedure. beta-cell dysfunction may need a longer high NEFA exposure.
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 09/2008; 30(4):509-15.
[show abstract][hide abstract] ABSTRACT: To evaluate islet beta cell response to intravenous glucagon (a non-glucose secretagogue) stimulation in diabetes mellitus.
Nineteen patients with type 1 diabetes (T1D) and 131 patients with type 2 diabetes (T2D) were recruited in this study. T2D patients were divided into two groups according to therapy: 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intravenous injection of 1 mg of glucagon.
Both fasting and 6-minute post-glucagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients (0.76 +/- 0.36 ng/mL vs. 1.81 +/- 0.78 ng/mL, P < 0.05; 0.88 +/- 0.42 ng/mL vs. 3.68 +/- 0.98 ng/mL, P < 0.05). In T1D patients, the C-peptide level after injection of glucagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy (2.45 +/- 0.93 ng/mL vs. 1.61 +/- 0.68 ng/mL, P < 0.05; 5.26 +/- 1.24 ng/mL vs. 2.15 +/- 0.76 ng/mL, P < 0.05). The serum C-peptide level after glucagon stimulation was positively correlated with C-peptide levels at fasting in all three groups (r = 0.76, P < 0.05).
The 6-minute glucagon test is valuable in assessing the function of islet beta cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.
Chinese Medical Sciences Journal 06/2008; 23(2):117-20.
[show abstract][hide abstract] ABSTRACT: To explore whether A1168C polymorphisms in paired box gene 4 (PAX4) are associated with type 1 diabetes mellitus (T1DM) in Chinese Han population.
Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to genotype A1168C polymorphisms in PAX4 gene. Totally 109 patients with T1DM and 251 control subjects were recruited. The frequency distributions of genotypes between two groups were analyzed by SPSS software.
The genotype distributions were in Hardy-Weinberg equilibrium both among T1DM cases and control subjects. No difference was observed in the genotype frequencies and allele frequencies between T1DM cases and control subjects (P > 0.05), nor was any disease association detected when patients were stratified according to age at diagnosis or sex (P > 0.05).
The A1168C single nucleotide polymorphism in PAX4 gene may not play an essential role in genetic T1DM susceptibility in Chinese Han population.
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 07/2007; 29(3):370-3.
[show abstract][hide abstract] ABSTRACT: To investigate the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes mellitus (T1DM) in the Chinese Han population.
One hundred and thirty-six Chinese Han people, including 54 T1DM patients and 82 unrelated healthy subjects as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism for three restriction sites in the VDR gene, which were ApaI, TaqI, and BamI.
The frequency of B allele of BsmI site in VDR gene was significantly higher in T1DM patients than in healthy subjects (P = 0.033) while no difference was found between the two groups in the distribution of ApaI and TaqI polymorphisms.
The BsmI polymorphism of VDR gene may be associated with the susceptibility to T1DM in the Chinese Han population of Beijing.
Chinese Medical Sciences Journal 07/2006; 21(2):95-8.
[show abstract][hide abstract] ABSTRACT: To investigate the relationship between glycosylated hemoglobin A1c (HbA1c) and blood glucose levels of eight different points throughout the day in well-glycemic-controlled medical nutrition therapy (MNT) alone type 2 diabetic patients.
Data were collected as' capillary blood glucose value of eight different sample points among sixteen observing days in thirty MNT alone type 2 diabetic patients. The correlation between HbA1c and capillary blood glucose value was evaluated by Pearson's correlation method.
The r-values between HbA1c and capillary blood glucose of 3:00, 6:00, and bedtime (22:00-23:00) were 0.81, 0.79, and 0.78, respectively (P < 0.001). The best correlation was found between the mean value of 8-point blood glucose value throughout the day and HbA1c (r = 0.84, P < 0.001).
Fasting blood glucose and postabsorptive blood glucose have better correlations with HbA1c compared with other points in this group of well-glycemic-controlled MNT alone type 2 diabetic patients.
Chinese Medical Sciences Journal 06/2006; 21(2):90-4.
[show abstract][hide abstract] ABSTRACT: To study the effect of insulin, cyclic adenosine monophosphate (cAMP), and dexamethasone (DEX) on 550 bp (-600 -/+ 69) fragment of phosphoenolpyruvate carboxykinase (PEPCK) gene promoter by reporter gene.
The recombinant pGL2-PEPCK-Luc and the control plasmid pSV-beta-Galactosidase were co-transfected to rat hepatoma cell line (CBRH7919) by lipofectin. By measuring luciferase activity, we evaluated in vitro regulation of PEPCK gene promoter on reporter gene transcription.
cAMP and DEX stimulated PEPCK promoter obviously; meanwhile, they also had accumulative effects. At different physiological concentrations, insulin had a suppressive effect on PEPCK promoter, which was dose-independent.
There is a perfect feedback mechanism for PEPCK promoter in hepatoma cell. 550 bp (-600 -/+ 69) fragment of PEPCK may be a candidate gene in the gene therapy of diabetes.
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 01/2005; 26(6):639-42.
[show abstract][hide abstract] ABSTRACT: To evaluate in vitro regulation of phosphoenolpyruvate carboxykinase (PEPCK) gene promoter on gene transcription, and construct luciferase reporter plasmid pGL2-PEPCK-Luc.
A 550 bp fragment of PEPCK promoter cut from plasmid pPEPCK-int was inserted into transitional vector PBS-SK to construct a transition plasmid PBS-PEPCK. Then the recombinant luciferase reporter plasmid pGL2-PEPCK-Luc was cloned.
Restriction enzymes and nucleotide sequence conformed that the coupling site of recombinant plasmid was correct without base mutation and deletion, and the sequence inserted was the same as data of GeneBank. The luciferase could be expressed in hepatoma cell transfected by pGL2-PEPCK-Luc.
Established a new means to study transcriptional regulation of PEPCK promoter.
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 11/2004; 26(5):562-5.