Showing papers by "Cheng Hu published in 2008"

Association of KCNJ11 and ABCC8 genetic polymorphisms with response to repaglinide in Chinese diabetic patients.

Abstract: Aim: The aim of this study was to investigate the association of KCNJ11 E23K and ABCC8 exon16–3T/C with the therapeutic effect of repaglinide in patients with type 2 diabetes. Methods: A total of 100 Chinese patients with newly diagnosed type 2 diabetes were treated with repaglinide for 24 weeks. Arginine stimulation tests were performed to evaluate beta cell function. Gene variations were detected with PCR-restriction fragment length polymorphism. Responders were defined by a greater than 25% decrease in fasting plasma glucose or a greater than 20% decrease in hemoglobin A1c (HbA1c) values (or both) after the 24 week repaglinide treatment. Results: Both baseline HbA1c and the decrease of HbA1c were significantly higher in patients with E/K and K/K genotypes of the KCNJ11 E23K variant when compared with E/E homozygotes (P=0.0103 and 0.0221, respectively). The decrease in 2 h postprandial plasma glucose (2hPG) was significantly greater in E/K heterozygotes than E/E homozygotes (P =0.0367). There was a significant difference in the response rate to repaglinide treatment between the E and K alleles (68% vs 82%, P =0.0324). The changes in fasting insulin and the homeostasis model assessment of insulin resistance were significantly greater in patients with ABCC8 exon16–3 C/C versus the T/C and T/T genotypes (P =0.0372 and 0.0274, respectively). Conclusion: The KCNJ11 E23K variant was associated with the therapeutic effect of repaglinide. In addition, The C/C homozygotes of the ABCC8 exon16–3T/C variant responded better to repaglinide in insulin sensitivity than the T/C and T/T genotypes.

Effect of RBP4 gene variants on circulating RBP4 concentration and Type 2 diabetes in a Chinese population

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 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.

Effects of ABCA1 variants on rosiglitazone monotherapy in newly diagnosed type 2 diabetes patients.

Abstract: Aim: The aim of the present study was to investigate the relationship between R219K, M883I, and R1587K variants of the ATP-binding cassette transporter subfamily A number 1 ( ABCA1 ) gene and response to rosiglitazone treatment in newly diagnosed patients with type 2 diabetes. Methods: A total of 105 diabetic patients with no history of antihyperglycemia medication were treated with rosiglitazone (4 or 8 mg daily) for 48 weeks. Three non-synonymous variants R219K, M883I, and R1587K, were genotyped in all patients. Results: Ninety-three patients completed the entire study. The R219K variant of ABCA1 had an effect on rosiglitazone response with the per-allele odds ratio of 2.04 for treatment failure ( P P Conclusion: The R219K variant of ABCA1 was associated with the therapeutic effect of rosiglitazone. The RR homozygotes had a better response to rosiglitazone treatment in terms of insulin sensitivity improvement than minor K allele carriers. Neither the M883I nor R1587K variant of the ABCA1 gene was associated with rosiglitazone response.

Glycemic variability and its responses to intensive insulin treatment in newly diagnosed type 2 diabetes

Abstract: Background: Recent data show that blood glucose (BG) variability is an HbA 1 c-independent risk factor for diabetic complications. This study investigated the characteristics of BG variability in type 2 diabetic patients and the effect of intensive treatment. Material/Methods: Forty-eight subjects with normal glucose regulation and 69 patients with newly diagnosed type 2 diabetes were monitored using tlie continuous glucose monitoring system. A subset of the type 2 diabetic patients (n=23) whose HbA 1 c was >8.5% was monitored a second time following 2 to 3 weeks of treatment with multiple daily injections. The mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), and the incremental areas above preprandial glucose values (AUCpp) were used for assessing intra-day, inter-day, and postprandial BG variability. Results: In type 2 diabetic patients, the MACE, MODD, and AUCpp levels were all higher than those of subjects with normal glucose regulation (P<0.001). Multivariant regression analysis indicated that AUCpp was the main independent factor influencing MAGE (Adjusted R 2 =0.56), while postprandial hyperglycemia was most prominent following breakfast and less evident during lunch and dinner. After intensive treatment, significant decreases in MAGE, MODD, and AUCpp were observed (41%, 29%, and 49%, respectively, P<0.001). AUCpp after breakfast was higher than after lunch and dinner (P<0.05). In 65.2% of the subjects, peak intra-day values occurred 103±30 minutes after breakfast. Conclusions: Minimizing glycemic variability in type 2 diabetic patients, especially postprandial glucose excursions following breakfast, may be an important aspect of glucose management.

[Genetic characteristics of familial type 2 diabetes pedigrees: a preliminary analysis of 4468 persons from 715 pedigrees].

Abstract: Obiective To analyze the inheritance character of type 2 diabetes mellitus(T2DM)pedigrees.Methods 4468 persons from 715 T2DM pedigrees(including the spouses)undergo peripheral blood sample collection to examine blood sugar and physical examination.Questionnaire survey was conducted to explore the family history.Type 1 DM and maturity-onset DM of young people were to be ruled out.Pedigree chart were made.Results The prevalence rates of 12 DM and impaired glucose regulation(IGR)wsa 47.62%,including 218 T2DM and 422 IGR newly discovered.The prevalence rates of T2DM and IGR were 38.33% and 14.25% in the siblings,and 56.81% and 12.58% in the parents,all significantly higher than those in the second-degree relatives(9.55% and 6.10%)and spouses(10.57% and 9.55% respectively,all P＜0.01).The prevalence and newly discovered rates of IGR in the offspring were 12.46% and 11.73% respectively,both significantly higher than those in the spouses(9.55% and 9.55% respectively,all P＜0.01).Conclusion There is significant familial aggregation in T2DM.The first-degree relatives of T2DM patients are high risk populations,so long term monitoring and early screening should be performed. Key words: Diabetes mellitus,type 2; Prevalence; Pedigree

[Relationship between blood glucose variability and microalbuminuria in type 2 diabetic patients with well-controlled glycosylated hemoglobin].

Abstract: Objective To investigate the relationship between the blood glucose variability and microalbuminuria (MAU) in type 2 diabetic patients with well-controlled glycosylated hemoglobin (HbAlc) and the influencing factors of blood glucose variability. Methods One hundred and seventy-six type 2 diabetic patients with HbAlc under 6.5% and 48 subjects with normal glucose regulation were monitored using the continuous glucose monitoring system (CGMS). The mean blood glucose (MBG) and mean amplitude of glucose excursions(MAGE) were analyzed. Results ( 1 ) The MBG and MAGE levels of type 2 diabetic patients were (7.0±0.9) and (3.8±2.5) mmol/L respectively, both higher than those of the subjects with normal glucose regulation [ (5.4±0.6) and (2.0±0.7) mmol/L respectively, both P< 0.01]. (2)The incidence ratio of MAU of the patients with ascended SAGE level was 18.7%, significantly higher of those with normal MAGE (7.1%, P<0.05). (3) The SAGE level was positively correlated with age, duration of diabetes, and systolic blood pressure, and negatively correlated with glomerular fdtration rate and the levels of fasting and postprandial C-peptide. Multivariant regression analyses indicated that duration of diabetes and the level of postprandial C-peptide 30 min after meal were the independent influential factors of MAGE. (4) In the type 2 diabetic patients, the MAGE of the MAU group was higher than that of the non-MAU group (P<0.05). Logistic regression analyses indicated that diastolic blood pressure and MAGE were the risk factors of MAU (OR=1.201 and 1.357, both P<0.05). Conclusion In weB-controlled patients with type 2 diabetes, blood glucose variability is one of the risk factors for MAU, duration of diabetes and early stage of insulin secretion function are the main factors influencing glycemic variability. Key words: Diabetes mellitus, type 2; Albuminuria; Continuous glucose monitoring

Association of variants in APPL1 gene with body fat and its distribution in Chinese patients with type 2 diabetic mellitus

Abstract: Objective To investigate the impact of single nucleotide polymorphisms(SNPs)in APPL1 gene on body fat and its distribution.Methods 590 unrelated Shanghai residents of Han nationality,including 358 subjects with normal glucose tolerance(NGT)and 232 subjects with type 2 diabetes mellitus(rT2DM),underwent measurement of body mass index(BMI),waist circumference(W),hip circumference(H),and femoral circumference(F).Peripheral blood samples were collected to detect the blood sugar,blood lipids,fasting C-peptide(FCP),fasting insulin(FINS),fasting plasma glucose (FGLU),total cholesterol(TC),and triglyceride(TG)0 and 120 minutes after glucose challenge.Polymerase chain reaction-restriction fragment length polymorphism was used to detect the 2 SNPs (rs3806622 and rs4640525).Results No differences in the frequencies of rs3806622 and rs4640525 genotypes between the subjects with the BMI＜25 kg/m2 and those with the BMI≥25 kg/m2 either in the NGT group or T2DM group.The G allele frequencies of the rs3806622 and rs4640525 genotypes in the T2DM patients with longer W values were significantly higher than those in the patients with shorter W value (OR=2.26,95%CI 1.05-4.86,and OR=4.13,95%CI 1.21-14.09).The W values of the T2DM subiects with G alleles were significantly higher than those of the T2DM subjects without G alleles after adjustment of age,sex,and BMI(all P＜0.05).Stepwise regression analysis showed that in addition to sex and BMI,rs4640525 was also an associated factor of waist circumference(all P＜0.05).Conclusion SNPs(rs3806622 and rs4640525)in APPL1 gene are correlated with body fat distribution in T2DM. Key words: Diabetes mellitus,Non-insulin-dependent; Single nucleotide polymorphisms; Gene

An evaluation of the performance of HapMap SNP data in a Shanghai Chinese population: Analyses of allele frequency, linkage disequilibrium pattern and tagging SNPs transferability on chromosome 1q21-q25

Abstract: The HapMap project aimed to catalog millions of common single nucleotide polymorphisms (SNPs) in the human genome in four major populations, in order to facilitate association studies of complex diseases. To examine the transferability of Han Chinese in Beijing HapMap data to the Southern Han Chinese in Shanghai, we performed comparative analyses between genotypes from over 4,500 SNPs in a 21 Mb region on chromosome 1q21-q25 in 80 unrelated Shanghai Chinese and 45 HapMap Chinese data. Three thousand and forty-two SNPs were analyzed after removal of SNPs that failed quality control and those not in the HapMap panel. We compared the allele frequency distributions, linkage disequilibrium patterns, haplotype frequency distributions and tagging SNP sets transferability between the HapMap population and Shanghai Chinese population. Among the four HapMap populations, Beijing Chinese showed the best correlation with Shanghai population on allele frequencies, linkage disequilibrium and haplotype frequencies. Tagging SNP sets selected from four HapMap populations at different thresholds were evaluated in the Shanghai sample. Under the threshold of r2 equal to 0.8 or 0.5, both HapMap Chinese and Japanese data showed better coverage and tagging efficiency than Caucasian and African data. Our study supported the applicability of HapMap Beijing Chinese SNP data to the study of complex diseases among southern Chinese population.

[Association of -6735T-->C variant of glucokinase-associated dual-specificity phosphatase 12 gene with type 2 diabetes in Chinese].

Abstract: Objective To investigate the impact of glucokinase-associated dual-specificity phosphatase 12 gene (DUSP12) single nucleotide polymorphism (SNP) on type 2 diabetes mellitus in Chinese. Methods The genotypes of -6735T→C of DUSP12 were determined by PCR-RFLP in 577 Chinese in Shanghai, 359 with normal glucose tolerance (NGT) and 218 being newly diagnosed DM patients without taking any drug. Oral glucose tolerance test was conducted. Height, weight, glucose and insulin concentrations, serum lipid profiles, and fat distribution parameters were determined. Results The genotype frequency distributions of -6735T→C variant in DUSP12 gene of the DM group and NGT group were not significantly different ( all P 0.05 ). The fasting plasma glucose concentration of the NGT subjects with C allele was 5.00 ( 4.69 - 5.28 ) mmol/L, significantly higher than that of the subjects with TT genotype [ 4. 90(4.50- 5.26 )mmol/L, P = 0. 035 ] . The serum HDL-c concentration of the NGT subjects with Callele was ( 1.25 ± 0.30 ) mmol/L, significantly lower than that of those with TT genotype [ ( 1.34 ± 0.30) mmol/L, P = 0. 010]. These two results still showed significant statistical differences after adjusted with sex, age, and BMI (P =0. 035). Conclusion -6735T→C variant in DUSP12 doesn't play a major role in diabetes, but it may have some effects on glucose and lipid metabolism. Key words: Diabetes,type 2; Polymorphism,single nucleotide

Study on the status of metabolic syndrome in familial type 2 diabetes pedigrees

Abstract: Objective To investigate the prevalence of metabolic syndrome (MS) and its components in type 2 diabetes meUitus pedigrees. Methods A total number of 4468 subjects (including spouses) from 715 type 2 diabetic pedigrees were selected in this study. Complete laboratory data including blood pressure, lipid profile and plasma glucose, were collected. All subjects who were not defined as diabetic were valued by oral glucose tolerance test. MS was diagnosed according to the definition proposed by the China Diabetes Society (CDS) in 2004. Results (1)The prevalence of MS was 23.86% in diabetic pedigrees, and subsequently increased in second-degree relatives, spouses, first-degree relatives and probands. (2)The prevalence rates of 'at least' 1 metabolic abnormality in first-degree relatives, second-degrcc relatives and spouses were 80.10 %, 59.76 % and 70.30 %, respectively. (3) Ratios on non-metabolic abnormality, 1-2 metabolic abnormality and MS were 19.90%, 55.02% and 25.08% in first-degree relatives, 40.24%, 50.82% and 8.94% in second-degree relatives, 29.70%, 53.31% and 16.99% in spouses, respectively. (4) Among the first-degree relatives, the common manifestation of metabolic abnormality was dyslipidemia for subjects aged below 40 years, and hyperglycemia for subjects aged over 40 years of age. (5)The prevalence of MS in first-degree relatives was higher in males than infemales for subjects aged below 60 and it was higher in females than in males for subjects aged over 60.Conclusion There was significant familial aggregation of MS found in our study. The first-degree relatives of type 2 diabetic patients were high risk populations, suggesting that early recognition and prevention were important issues to be carried out. Key words: Metabolic syndrome; Diabetes mellitus,type 2; Prevalence; Pedigree