Biomedical subjects

Weiping Jia

Publications and source records attributed to Weiping Jia.

9 recordsLinked to original sources

PubMed2006

The significance of tumor necrosis factor-alpha in newly diagnosed type 2 diabetic patients by transient intensive insulin treatment.

This study was performed to investigate whether transient intensive insulin therapy with an insulin pump (TIIT) can decrease serum tumor necrosis factor-alpha (TNF-alpha) and explore whether the decrease of serum TNF-alpha has correlation with the improvement of islet beta-Cell function and the decrease of insulin resistance. Thirty healthy volunteers served as control subjects. One hundred and thirty-eight newly diagnosed type 2 diabetic patients had been treated with TIIT for 2 weeks. TNF-alpha, free fatty acids (FFAs), glucose, and insulin (INS) had been measured before and after TIIT, respectively. Homeostasis model assessment (HOMA) was used to estimate insulin resistance (HOMA-IR) and islet beta-Cell function (HOMA-beta). TNF-alpha was significantly increased in diabetes. After TIIT, TNF-alpha, fasting blood glucose, FFAs, and HOMA-IR were significantly decreased. HOMA-beta and the areas under the curves of INS were significantly increased during intravenous glucose tolerance tests. TNF-alpha had not only significant negative correlation with the changes of insulin secretion, but also significant positive correlation with the changes of HOMA-IR after adjustment of blood glucose. Partial correlation analyses demonstrated that there was an indepenent relationship between TNF-alpha and HOMA-IR and HOMA-beta. Our study confirms that TIIT can effectively decrease serum TNF-alpha in type 2 diabetes. It is inferred that the decrease of serum TNF-alpha might be involved in the improvement of beta-Cell function and the decrease of insulin resistance by TIIT.

Area Under Curve↗

PubMed2006

Ala45Thr variation in neuroD1 gene is associated with early-onset type 2 diabetes with or without diabetic pedigree in Chinese.

OBJECTIVE: Based on onset-age stratified analysis may be useful to determine the association of NeuroD1-Ala45Thr variation with susceptibility to genetic heterogeneous type 2 diabetes mellitus (T2DM), we investigated the Ala45Thr variation in unrelated early-onset and late-onset T2DM with or without diabetic pedigree and unrelated non-diabetic control subjects in Chinese. METHODS: 175 early-onset and 194 late-onset type 2 diabetic patients were further divided into two subgroups according to with or without diabetic pedigree respectively. This NeuroD1-Ala45Thr variation were screened by PCR-direct sequencing in above 369 type 2 diabetic patients and 87 unrelated non-diabetic control subjects. We then compared the distribution of the Ala45Thr variation among the groups, searching for the predictive trends. RESULTS: Frequencies of the variant (AA + GA genotype) in early-onset T2DM are obviously elevated, especially among diabetic pedigree subjects when compared to non-diabetic controls (p= 0.003) and late-onset T2DM subjects (p = 0.014). However, no significant differences were observed between late-onset T2DM with or without diabetic pedigree and non-diabetic control subjects. CONCLUSIONS: Our results suggest that 1) the NeuroD1-Ala45Thr variation may itself have an important role in susceptibility to or be in disequilibrium with early-onset T2DM in Chinese; 2) the Ala45Thr may affect the onset pattern of T2DM, i.e., early-onset but not late-onset T2DM in Chinese; and 3) onset-age stratified analysis may be useful to determine the association of NeuroD1-Ala45Thr variation with susceptibility to genetic heterogeneous T2DM in Chinese.

Adult↗

PubMed2006

Variation within the gene encoding the upstream stimulatory factor 1 does not influence susceptibility to type 2 diabetes in samples from populations with replicated evidence of linkage to chromosome 1q.

The gene encoding the transcription factor upstream stimulatory factor (USF)1 influences susceptibility to familial combined hyperlipidemia (FCHL) and triglyceride levels. Phenotypic overlap between FCHL and type 2 diabetes makes USF1 a compelling positional candidate for the widely replicated type 2 diabetes linkage signal on chromosome 1q. We typed 22 variants in the F11R/USF1 region (1 per 3 kb), including those previously implicated in FCHL-susceptibility (or proxies thereof) in 3,726 samples preferentially enriched for 1q linkage. We also examined glucose- and lipid-related continuous traits in an overlapping set of 1,215 subjects of European descent. There was no convincing evidence for association with type 2 diabetes in any of seven case-control comparisons, individually or combined. Family-based association analyses in 832 Pima subjects were similarly negative. At rs3737787 (the variant most strongly associated with FCHL), the combined odds ratio, per copy of the rarer A-allele, was 1.10 (95% CI 0.97-1.24, P = 0.13). In 124 Utah subjects, rs3737787 was significantly associated (P = 0.002) with triglyceride levels, but direction of this association was opposite to previous reports, and there was no corroboration in three other samples. These data exclude USF1 as a major contributor to type 2 diabetes susceptibility and the basis for the chromosome 1q linkage. They reveal only limited evidence for replication of USF1 effects on continuous metabolic traits.

Adult↗

PubMed2004

Genome-wide search for type 2 diabetes/impaired glucose homeostasis susceptibility genes in the Chinese: significant linkage to chromosome 6q21-q23 and chromosome 1q21-q24.

This genome-wide search for susceptibility genes to type 2 diabetes/impaired glucose homeostasis (IGH) was performed on a relatively homogeneous Chinese sample with a total number of 257 pedigrees and 385 affected sibpairs. Two regions showed significant linkage to type 2 diabetes/IGH in the Chinese. The region showing linkage to type 2 diabetes/IGH from the entire sample group analysis was located on chromosome 6q21-q23 (128.93 cM, 1-LOD [logarithm of odds] support interval between 124 and 142 cM, according to the Marshfield genetic map), with a maximum likelihood score of 6.23, a nonparametric linkage (all) score of 4.48, and empirical P value <0.001. With a subanalysis based on 101 affected sibpairs with age at diagnosis of type 2 diabetes/IGH <40 years, we detected significant evidence for linkage to chromosome 1q21-q24 (192.1 cM, 1-LOD support interval between 182 and 197 cM), with a maximum likelihood score of 8.91, a nonparametric linkage (all) score of 5.70, and empirical P value <0.001. No interaction was observed between these two regions. Our independent replication of the region on chromosome 1q that has been shown to be linked significantly to type 2 diabetes/IGH in Chinese supports the notion that gene(s) in this region may be universally important in the development of human type 2 diabetes.

Asian People↗

PubMed2002

[The relationship between human serum resistin level and body fat content, plasma glucose as well as blood pressure].

OBJECTIVE: To investigate serum resistin concentration in essential hypertension patients and the relationship between serum resistin level and body fat content, plasma glucose concentration, and blood pressure. METHODS: Fasting serum resistin concentrations were measured with enzyme immunoassay in 71 cases (including 33 men and 38 women), and oral glucose tolerance test and insulin release test were performed in all cases for calculating glucose area under the curve (AUC(G)), the ratio of change in insulin to change in glucose during the first 30 min after glucose ingestion (Delta I(30)/Delta G(30)) and insulin sensitivity index (ISI) according to Cederholm's formula. Systolic pressure (SBP), diastolic pressure (DBP), height, body weight, waist circumference and hip circumference were measured to calculate body mass index (BMI), body fat percentage (BF%) and waist-hip ratio (WHR). RESULTS: Pearson analysis showed that fasting serum resistin concentrations were correlated with AUC(G) (r = 0.380, P < 0.001), BF% (r = 0.353, P < 0.01), ISI (r = -0.242, P < 0.05) and Delta I(30)/Delta G(30) (r = -0.298, P < 0.05), but not correlated with SBP, DBP, BMI and WHR. After adjustment for age and BMI, partial correlation analysis showed that fasting serum resistin concentrations were correlated with AUC(G) (r = 0.268, P < 0.05), Delta I(30)/Delta G(30) (r = -0.247, P < 0.05) and not correlated with ISI. A stepwise multiple linear regression analysis showed that resisitin was a significant independent predictor of AUC(G). CONCLUSION: The strong correlation between fasting serum resistin levels and AUC(G), and BF% suggests a possibility that resistin link obesity to diabetes in humans.

Blood Glucose↗

PubMed2002

Accelerating the drug optimization process: identification, structure elucidation, and quantification of in vivo metabolites using stable isotopes with LC/MSn and the chemiluminescent nitrogen detector.

Most preclinical leads exhibit poor ADME/PK properties and require optimizing to increase the likelihood of becoming successful pharmaceuticals. As a means of accelerating the evaluation of these leads in vivo, we assessed the use of LC/MS with the chemiluminescent-nitrogen detector (CLND) and a stable isotope to identify and quantify in vivo metabolites and to measure excretion. A 14C-labeled preclinical lead that also contained two chlorine atoms was administered orally to rats, and samples of bile, urine, and plasma were collected and analyzed by LC with radiodetection and by LC/MS-CLND with the chlorine atoms used as tracers. Both methods identified seven metabolites in bile and two metabolites in urine. The amount and abundance of each metabolite was measured, and the results were equivalent for the two methods. Material balance was measured by liquid scintillation counting of the starting samples, by LC/radiodetection, and by LC/MS-CLND. All three methods yielded the same results and showed that the primary route of clearance was metabolism followed by immediate excretion. This study demonstrates that LC/MS-CLND with a stable isotope is a method that can efficiently track and accurately quantify metabolites, making it possible to rapidly study ADME/PK in vivo without radiolabeling.

Animals↗

PubMed2002

[The UCSNP44 variation of calpain 10 gene on NIDDM1 locus and its impact on plasma glucose levels in type 2 diabetic patients].

OBJECTIVE: To study the contribution of single nucleotide polymorphism-UCSNP44 at calpain-10 gene (CAPN-10) on NIDDM1 locus to type 2 diabetes mellitus (T2DM) in Chinese. METHODS: 276 Chinese living in Shanghai, 148 with normal glucose tolerance (NGT) and 128 with T2DM were given 75 g glucose. O, 30, 60, 120, and 180 minutes later their plasma glucose (PG), insulin (INS), C-peptide (CP), and free fatty acids (FFA) were measured and the areas under curve (AUC) were calculated. The islet beta-cell insulin secretion and tissue insulin sensitivity were estimated by formulae of homeostasis model assessment and increment ratio of insulin to glucose levels 30 minutes after glucose challenge. The CAPN-10 UCSNP44 as well as UCSNP43 were genotyped by automated DNA direct sequencing. RESULTS: (1) The major genotype of CAPN-10 UCSNP44 in persons with NGT was TT (with a frequency of 0.82); the major allele was T (0.91). The most frequent genotype combination between UCSNP44 and UCSNP43 was TT-GG (corresponding to haplotype combination TG/TG) (0.64). The most frequent haplotype was TG (0.80). The D value for linkage disequilibrium between UCSNP44 and UCSNP43 was -0.11. (2) The frequencies of UCSNP44 and UCSNP44/UCSNP43 haplotype combination did not differ significantly between subjects with NGT and those with T2DM. (3) The PG levels in T2DM subjects with UCSNP44 TT genotype both at fasting and after glucose challenge were statistically significantly higher than those in subjects with non-TT (TC + CC) genotype, especially the PG levels 0, 60, 120, and 180 minutes after glucose challenge (P = 0.036, 0.040, 0.020, and 0.017) and the PG-AUC (P = 0.013). The PG levels and PG-AUC 0 and 120 minutes after glucose challenge were still significant after adjusted with age, sex, and body mass index and waist circumference. Similar results were observed in comparison between the TG/TG and TG/CG subgroups of UCSNP44/UCSNP43 haplotype combination. In addition, T2DM subjects with UCSNP44 TT genotype had lower CP levels after glucose challenge than those with non-TT genotype. However, the difference became not statistically significant after adjusted with above-mentioned variables. CONCLUSION: The variation of CAPN-10 UCSNP44 has an impact on plasma glucose levels at fasting and after glucose challenge in subjects with type 2 diabetes. The relevant mechanism remains to be elucidated.

Blood Glucose↗

PubMed2002

[Evaluation of abdominal visceral obesity from anthropometric parameters using receiver operating characteristic curves].

OBJECTIVE: To evaluate the best cut-off point, sensitivity and specificity of body mass index (BMI), waist circumference (WC) and Waist-to-hip ratio (WHR) in predicting of abdominal visceral obesity. METHODS: Abdominal visceral fat area (VA) was measured with magnetic resonance image (MRI) in 690 subjects (men: 305, women: 385). Meanwhile, BMI, WC, WHR were assessed. Receiver operating characteristic (ROC) curve was used as index for analysis. RESULTS: 1) 61.7% of over-weight/obesity (OW/OB) and 14.2% of normal weight (NW) individuals were abdominal visceral obesity (VA >/= 100 cm(2)) by MRI diagnosis. 2) VA was significantly positively correlated with anthropometric variables (BMI, WC, WHR), in which WC was the best (r = 0.73 - 0.77, P < 0.001). 3) The best cut-off points of these anthropometric parameters in assessing abdominal visceral obesity were as follow: BMI: 26 kg/m(2), WC: 90 cm, WHR: 0.93. Among them WC showed most sensitive and specific. 4) 95% men and 90% women appeared abdominal visceral obesity in subjects with BMI >/= 28 kg/m(2) or WC >/= 95 cm. CONCLUSION: BMI, WC, WHR can all predict abdominal visceral obesity, with WC the best.

Adipose Tissue↗

PubMed2002

[Effects of uncoupling protein 3 gene -55 C-->T variant on lipid metabolism, body fat, its distribution and non-insulin-dependent diabetes mellitus in Chinese].

OBJECTIVE: To investigate the relationship of UCP3 gene -55 C-->T variant with lipid metabolism, body fat, its distribution and non-insulin-dependent diabetes mellitus(NIDDM) in Chinese. METHODS: Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) was used to detect the genotype of UCP3 gene -55 C-->T in a total of 316 Chinese including 165 individuals with normal glucose tolerance(NGT) and 151 patients with type 2 diabetes). MRI was used to detect local body fat; the enzyme method and sulfate-sephadex-manganese precipitation method were used to detect TC and HDL-C, and then LDL-C was calculated with corresponding formula. RESULTS: (1)No difference was seen on comparing allele and genotype frequencies of Chinese with those of Caucasian (P=0.1120 and P=0.0646, respectively), whereas significant difference in these frequencies was seen between Chinese and Pima Indians(P=0.0 105 and P=0.0314, respectively). (2)Stepwise regression analysis revealed that the independent variables to UCP3 gene -55 C-->T were: HDL-C(P= 0.013)and LDL-C(P=0.012) in male NGT subgroup FA(P=0.023) in female NGT subgroup TG(P=0.004)in male DM subgroup, and waist to hip ratio (WHR)(P=0)in female DM subg roup. (3)The allele frequency of DM group was significantly different from that of NGT(P =0.0358). The odd ratio for the T allele carrier with NIDDM was 1.434 (95%CI 1.031-1.995). CONCLUSION: Although UCP3 gene 55 C-->T variant is associated with lipid metabolism, body fat and its distribution in Chinese, the association is dependent on sex and disease status. The variant is also associated with NIDDM in Chinese.

Adipose Tissue↗