Xin-Hua Xiao

Peking Union Medical College Hospital, Peping, Beijing, China

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Publications (13)4.97 Total impact

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    ABSTRACT: Background: Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variants in genes CDKAL1, HHEX, ADCY5, SRR, PTPRD that predisposed to type 2 diabetes were also associated with reduced birthweight in Chinese Han population. Methods: Twelve single nucleotide polymorphisms (rs7756992/rs10946398 in CDKAL1, rs1111875 in HHEX, rs391300 in SRR, rs17584499 in PTPRD, rs1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243 in ADCY5) were genotyped in 1174 unrelated individuals born in Peking Union Medical College Hospital from 1921 to 1954 by TaqMan allelic discrimination assays, of which 645 had normal glucose tolerance, 181 had developed type 2 diabetes and 348 impaired glucose regulation. Associations of these 12 genetic variants with birthweight and glucose metabolism in later life were analyzed. Results: Birthweight was inversely associated with CDKAL1-rs10946398 (β = -41 g [95% confidence interval [CI]: -80, -3], P = 0.034), common variants both associated with increased risk of impaired glucose metabolism and decreased insulin secretion index later in life. After adjusting for sex, gestational weeks, parity and maternal age, the risk allele of CDKAL1-rs7756992 was associated with reduced birthweight (β = -36 g [95% CI: -72, -0.2], P = 0.048). The risk allele in SRR showed a trend toward a reduction of birthweight (P = 0.085). Conclusions: This study identified the association between type 2 diabetes risk variants in CDKAL1 and birthweight in Chinese Han individuals, and the carrier of risk allele within SRR had the trend of reduced birthweight. This demonstrates that there is a clear overlap between the genetics of type 2 diabetes and fetal growth, which proposes that lower birth weight and type 2 diabetes may be two phenotypes of one genotype.
    No preview · Article · Jul 2015 · Chinese medical journal
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    ABSTRACT: Chromium is an essential mineral that is thought to be necessary for normal glucose homeostasis. Numerous studies give evidence that chromium picolinate can modulate blood glucose and insulin resistance. The main ingredient of Tianmai Xiaoke (TMXK) Tablet is chromium picolinate. In China, TMXK Tablet is used to treat type 2 diabetes. This study investigated the effect of TMXK on glucose metabolism in diabetic rats to explore possible underlying molecular mechanisms for its action. Diabetes was induced in rats by feeding a high-fat diet and subcutaneously injection with a single dose of streptozotocin (50 mg/kg, tail vein). One week after streptozotocin-injection, model rats were divided into diabetic group, low dose of TMXK group and high dose of TMXK group. Eight normal rats were used as normal control. After 8 weeks of treatment, skeletal muscle was obtained and was analyzed using Roche NimbleGen mRNA array and quantitative polymerase chain reaction (qPCR). Fasting blood glucose, oral glucose tolerance test and homeostasis model assessment of insulin resistance (HOMA-IR) index were also measured. We found that the administration of TMXK Tablet can reduce the fasting blood glucose and fasting insulin level and HOMA-IR index. We also found that 2 223 genes from skeletal muscle of the high-dose TMXK group had significant changes in expression (1 752 increased, 471 decreased). Based on Kyoto encyclopedia of genes and genomes pathway analysis, we found that the most three significant pathways were "insulin signaling pathway", "glycolysis/gluconeogenesis" and "citrate cycle (TCA)". qPCR showed that relative levels of forkhead box O3 (FoxO3), phosphoenolpyruvate carboxykinase 2 (Pck2), and protein tyrosine phosphatase 1B (Ptp1b) were significantly decreased in the high-dose TMXK group, while v-akt murine thymoma viral oncogene homolog 1 (Akt1) and insulin receptor substrate 2 (Irs2) were increased. Our data show that TMXK Tablet reduces fasting glucose level and improves insulin resistance in diabetic rats. The mechanism may be linked to the inactivation of PTP1B and PCK enzymes, or through intracellular pathways, such as the insulin signaling pathway.
    No preview · Article · Apr 2014 · Journal of integrative medicine
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    ABSTRACT: A rapid resolution liquid chromatography. mass spectrometric (RRLC-MS) method was developed and validated for the determination of endogenous lipid metabolites in human serum. The samples were pretreated by lipid extraction with methylene chloride. methanol (2: 1, V/V) mixture solvent and introduced to RRLC. MS under intensive optimization of chromatography conditions and mass spectrometry parameters. The chromatographic separation was performed on an ACQUITY UPLC CSH C-18 column (100 mm x 2. 1 mm, 1. 7 mu m) with mobile phase containing 10 mmol/L ammonium formate (0. 1% formic acid) (A) and acetonitrile. isopropyl alcohol (1: 1, V/V) mixture solution (B) in a linear gradient elution. The MS detection was carried out by the integrated ionization approach using electrospray ionization (ESI) in both positive and negative ion modes and atmosphere pressure chemical ionization (APCI) in positive ion mode. Typical lipid molecules such as free fatty acids (FFAs), phospholipids (PLs), sphingophosphalipids (SPs), glycerolipids (GLs), cholesterol (Chol.) and cholesterol esters (CEs) had been detected with high sensitivity, good precision and reliable stability. Furthermore, the principal component analysis (PCA) results of the quality control (QC) samples among the real sample queue indicated the data reliability of the method in lipidomics applications.
    No preview · Article · Sep 2013 · CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
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    ABSTRACT: Glucose is derived from three sources: intestinal absorption, glycogenolysis, and gluconeogenesis. Hypoglycemia in child is often attributed to depletion of glycogen stores. However, recently, congenital hyperinsulinism becomes an important cause of hypoglycaemia in early infancy. Mutations in the genes encoding SUR1 and KIR6.2 are the most frequent genetic causes of hyperinsulinism followed by mutations in the glutamate dehydrogenase (GDH) gene which encodes hyperinsulinism/hyperammonaemia (HI/HA) syndrome.1 HI/HA syndrome was first reported by Zammarchi et al2 in 1996. In 1998, Stanley et al3 found that the mutations in the GDH gene are the reason of HI/HA syndrome. Here we describe a boy with a severe form of HI/HA syndrome with a GDH gene mutation, which had never been reported in China before, and evaluated the efficacy of oral carbohydrateprotein-adipose tolerance test in the diagnosis. We also designed a test to choose a proper ratio between carbohydrate and protein in its treatment, whereas six-month follow-up showed that dietary therapy could be a useful treatment.
    Preview · Article · Jul 2010 · Chinese medical journal
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    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.
    Full-text · Article · Jul 2010 · Chinese medical journal
  • Wen-hui Li · Xin-hua Xiao · Kang Yu · Qi Sun · Guo-hua Yang · Heng Wang · Schmitz Ole
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    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.
    No preview · Article · Sep 2008 · Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae
  • Tong Wang · Xin-Hua Xiao · Wen-Hui Li · Heng Wang · Qi Sun · Tao Yuan · Guo-Hua Yang
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    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.
    No preview · Article · Jun 2008 · Chinese Medical Sciences Journal
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    Tong Wang · Xin-hua Xiao · Wen-hui Li · Tao Yuan · Xiao-fang Sun · Heng Wang

    Preview · Article · Feb 2008 · Chinese medical journal
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    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.
    No preview · Article · Jul 2007 · Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae
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    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.
    No preview · Article · Jul 2006 · Chinese Medical Sciences Journal
  • Wen-Hui Li · Xin-Hua Xiao · Qi Sun · Guo-Hua Yang · Heng Wang
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    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.
    No preview · Article · Jun 2006 · Chinese Medical Sciences Journal
  • Kai Feng · Heng Wang · Qi Sun · Xin-Hua Xiao
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    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.
    No preview · Article · Jan 2005 · Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae
  • Kai Feng · Heng Wang · Qi Sun · Xin-hua Xiao
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    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.
    No preview · Article · Nov 2004 · Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae