Association of a SLC30A8 genetic variant with monotherapy of repaglinide and rosiglitazone effect in newly diagnosed type 2 diabetes patients in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate a potential relationship between Solute carrier family 30 (zinc transporter) member 8 (SLC30A8) rs13266634 variant and efficacy of rosiglitazone or repaglinide in treating newly diagnosed Chinese type 2 diabetes patients.</p><p><b>METHODS</b>A total of 209 diabetic patients without any antihyperglycemic history were recruited and treated with repaglinide or rosiglitazone randomly for 48 weeks (104 and 105 patients, respectively). Anthropometric measurements and clinical laboratory tests were carried out before and after the treatment. An non-synonymous variant rs13266634 was genotyped by matrix-assisted laser desorption ionization-time of flight mass spectroscopy.</p><p><b>RESULTS</b>Ninety-one patients in repaglinide group and ninety-three patients in rosiglitazone group completed the study. Δ value of homeostasis model assessment of beta cell function (HOMA-B) and Δ value of fasting proinsulin levels were statistically significant between three genotype groups (P=0.0149 and 0.0246, respectively) after rosiglitazone treatment. However, no genotype association was observed in the repaglinide or rosiglitazone group with other parameters.</p><p><b>CONCLUSION</b>The SLC30A8 variant was associated with the efficacy of insulin sensitizer monotherapy on insulin secretion in patients with newly diagnosed type 2 diabetes mellitus in Shanghai, China.</p>

No association of vascular endothelial growth factor A gene rs9369425 polymorphism with glucose metabolism in Chinese Han population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the vascular endothelial growth factor A gene (VEGFA) rs9369425 single nucleotide polymorphism (SNP) and type 2 diabetes in Chinese Han population.</p><p><b>METHODS</b>One thousand eight hundred and ninety two type 2 diabetes patients and 1808 controls with normal glucose were recruited in this study. Phenotypes including body mass index, waist, waist hip ratio, plasma glucose and serum insulin levels of blood obtained both at 0 and 120 minute during standard 75-gram glucose oral glucose tolerance tests, were analyzed. Insulin resistance and beta cell function were assessed by homeostasis model assessment (HOMA-IR and HOMA-B). Genotyping was performed by time-of-light mass spectrum using a Sequenom platform.</p><p><b>RESULTS</b>The frequencies of minor allele G in the diabetic patients and controls were 10.8% and 11.3% respectively. No significant difference of allele distribution was detected between the cases and controls (P=0.5086). No significant difference (P>0.05) was detected on the association between rs9369425 SNP and clinical phenotypes.</p><p><b>CONCLUSION</b>VEGFA rs9369425 was not associated with type 2 diabetes in Chinese Han population. Whether there is association in any other loci in this gene remained to be investigated.</p>

Comparison of body mass index with body fat percentage in the evaluation of obesity in Chinese / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the present Chinese body mass index (BMI) criteria with body fat percentage (BF%) in determining obesity in Chinese population.</p><p><b>METHODS</b>A total of 4 907 subjects (age: 20-90 yrs) were enrolled in the baseline survey of a longitudinal epidemiological study, and 2 638 of them were reevaluated in 5.5 years later. The Chinese BMI and WHO BF% were used to define obesity, respectively.</p><p><b>RESULTS</b>The diagnostic agreement between the Chinese BMI and WHO BF% definitions for obesity was poor for both men (kappa: 0.210, 95% CI: 0.179-0.241) and women (kappa: 0.327, 95% CI: 0.296-0.358). However, BMI had a good correlation with BF% both in men (r: 0.785, P<0.01) and women (r: 0.864, P<0.01). The age and sex-adjusted relative risks (RR) for incidence of type 2 diabetes (T2DM) were significantly higher in subjects with intermediate BF% (BF%:20.1%-25% for men, 30.1%-35% for women) (RR: 2.35, 95% CI: 1.23-4.48) and high BF%(BF%>25% for men and > 35% for women)(RR: 2.89, 95% CI: 1.43-5.81), or in subjects with high BMI (BMI>or=28 kg/m(2)) (RR: 2.46, 95% CI: 1.31-4.63) when compared to those with low BF% (BF%<or=20% for men and<or=30% for women) or low BMI (BMI24 kg/m(2)) respectively. No difference in risk could be found in those with intermediate BMI (BMI: 24-27.9 kg/m(2)) (RR: 1.44, 95% CI: 0.86-2.40), as compared to those with low BMI (BMI<24 kg/m(2)), whose BF% ranged widely from 7.8 to 50.3%.</p><p><b>CONCLUSION</b>BMI was correlated with BF%. Both BMI and BF% were associated with high risk for T2DM. However, BMI had its limitations in the interpretation of subjects with BMI between 24 and 27.9 kg/m(2).</p>

Study on the mitochondrial DNA mutations in familial diabetes mellitus in Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the prevalence of mutations or variants of the mitochondrial DNA (mtDNA) in familial diabetes mellitus in Chinese population, and to explore the relationship between mtDNA mutations or variants and diabetes.</p><p><b>METHODS</b>Seven hundred and seventy randomly selected, unrelated probands of diabetes pedigrees and 309 controls over 60 years of age with normal glucose tolerance were recruited. PCR-RFLP and PCR-direct sequencing were applied to the screening of mtDNA mutations or variants, including the mutations at nucleotides 3243, 3256 in tRNALeu region, 12258 in tRNASer region, 14709 in tRNAGlu region, 8296, 8344, 8363 in tRNALys region, 3316, 3394, 3426 in ND1 region and 12026 in ND4 region.</p><p><b>RESULTS</b>In the diabetic group, 13 (1.69%) had mt3243 A>G mutation, 9(1.17%) had tRNAGlu 14709 T>C variant, 17 (2.21%) carried mt3316 G>A variant, 18 (2.34%) had mt3394 T>C variant, and 28 (3.63%) harbored the 12026 A>G variant. In the control group, the 14709, 3316, 3394, 12026 variants were detected in 5(1.62%), 5(1.62%), 6(1.94%), and 9(2.91%) subjects respectively. The 3256, 8296, 8344, 8363, 3426 and 12258 point mutations were not detected both in the diabetic patients and the controls. In the diabetic group, we found two double mutations, one was A3243G and T3394C, the other was A3243G and A12026G. Except that the A3243G mutation was only observed in the diabetic group, the frequencies of the other variants mentioned above were not statistically different between the diabetic and control groups. Moreover, clinical characteristics such as age of onset, BMI, and insulin resistance index were not different between diabetic patients with and without the variants.</p><p><b>CONCLUSION</b>The tRNA (LeuUUR) 3243 A>G mutation may be the major cause of diabetes, representing 1.69% of the familial diabetes mellitus in Chinese. The other variants may be polymorphisms in this population, and the mutations not detected in our studied population may not be common contributors to diabetes mellitus in Chinese.</p>

Relationship of plasma creatinine and lactic acid in type 2 diabetic patients without renal dysfunction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>As one of most widely-used biguanides, metformin can induce the lactic acidosis in patients with renal failure though its incidence is very low. However, lactic acidemia induced by metformin was reported in patients without renal dysfunction. It is unclear that whether lactatemia exists in diabetic patients with normal renal function in Chinese or not and its influencing factors. This study aimed to clarify the influencing factors of lactic acid, and identify a practiced clinical marker to predict the hyperlactacidemia in diabetics with normal renal function.</p><p><b>METHODS</b>The clinical data and venous blood samples of 1024 type 2 diabetic patients treated with (n = 426) or without metformin (n = 599) were collected. The lactic acid was assayed by enzyme-electrode method. The biochemical indexes included creatinine (Cr) and hepatase were measured with enzymatic procedures. The lactic acid concentrations of different Cr subgroups were compared, and the correlation and receiver operating characteristic curve analysis were used.</p><p><b>RESULTS</b>The mean lactic acid level and the proportion of hyperlactatemia of metformin group were significantly higher than that of non-metformin group (P < 0.01), but no lactic acidosis was found in all patients. The correlation and multiple stepwise regression analysis indicated that the correlative factors of lactic acid in turn were Cr, metformin, alanine transferase (ALT), body mass index (BMI), Urine albumin (Ualb), and blood urea nitrogen (BUN) in total patients; and Cr, ALT, BMI and BUN in non-metformin treated patients; Cr and ALT in metformin-group. The lactate concentration increased with the increment of Cr levels, and reached its peak at Cr 111-130 micromol/L, and the optimal cutoff of Cr in predicting hyperlactacidemia was 96.5 micromol/L.</p><p><b>CONCLUSIONS</b>Metformin can increase the incidence of lactatemia in type 2 diabetic patients without renal dysfunction. Cr, ALT, and BMI are independent associated factors of blood lactic acid levels. There is low proportion of lactatemia in type 2 diabetics without metformin therapy, the optimal cutoff of Cr to predict lactatemia in these patients is 96.5 micromol/L.</p>

Comparison of the application of three diagnostic criteria of metabolic syndrome in familial type 2 diabetic pedigrees / 中华预防医学杂志

<p><b>OBJECTIVE</b>To compare the significance of the application of three diagnostic criteria of metabolic syndrome (MS), issued by the National Cholesterol Education Program Adult Treatment Panel II (ATPIII) in 2005, International Diabetes Federation (IDF) in 2005 and Chinese Diabetes Society (CDS) in 2004, in type 2 diabetes mellitus pedigrees.</p><p><b>METHODS</b>Totally,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. The prevalence rates of MS and the unity of three criteria were analyzed.</p><p><b>RESULTS</b>The prevalence rates of MS were 44.94% (2008/4468), 37.87% (1692/4468) and 23.86% (1066/4468) according to the ATPIII, IDF and CDS criteria respectively. It subsequently increased in second-degree relatives, spouses, first-degree relatives and probands (ATP III: 23.78% (117/492), 35.77% (318/889), 45.40% (1077/2372) and 69.37% (496/715); IDF: 20.53% (101/492), 31.61% (281/889), 38.74% (919/2372) and 54.69% (391/715); CDS: 8.94% (44/492), 16.99% (151/889), 25.08% (595/2372) and 38.60% (276/715); ATPIII: chi2 = 266.359, IDF: chi2 = 155.950, CDS: chi2 = 165.087, respectively, P < 0.01). The prevalence rates of MS, as defined by the ATP III and IDF criteria, were higher in females than in males (ATP III: 47.47% (1156/2435) and 41.91% (852/2033); IDF: 43.00% (1047/2435) and 31.73% (645/2033); chi2 = 13.871 and 60.169, respectively, P < 0.01), and was lower in females than in males as defined by the CDS criterion (22.38% and 25.63%, respectively, chi2 = 6.423, P = 0.011). The agreement in the diagnosis of MS using ATPIII and IDF, ATPIII and CDS, IDF and CDS was 92.93%, 75.56% and 77.21% respectively. Kappa index were 0.855, 0.484 and 0.478 respectively (P < 0.01).</p><p><b>CONCLUSION</b>ATP III criterion showed the highest prevalence of MS and the percent of risk factor aggregation which best reflected the characteristics of MS in familial type 2 diabetic pedigrees.</p>

Prevalence and clinical characteristics of the mitochondrial tRNA(Leu(UUR)) gene 3243 A to G mutation in familial diabetes mellitus in Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the prevalence and clinical characteristics of the A to G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene in familial diabetes in Shanghai, Jiangsu and Zhejiang Province of China.</p><p><b>METHODS</b>The mt3243 A to G mutation in 770 randomly selected, unrelated probands of diabetic pedigrees were screened by PCR-RFLP technique and PCR-direct sequencing. Genetic and clinical analyses were further performed in the probands and their family members.</p><p><b>RESULTS</b>Thirteen diabetic patients (13/770, 1.69%) with mt3243 A to G mutation were detected. Eleven diabetic patients and 8 normal glucose tolerance (NGT) first-degree relatives of these 13 probands were also found bearing the mutation. Seventeen patients were associated with sensory hearing loss. In the 24 patients harboring the mutation, the majority had lower body mass index (BMI), 18 showed typical maternal inheritance, 15 had sensory hearing loss, 13 had insulin resistance and 14 required insulin therapy due to secondary failure to oral hypoglycemic agents.</p><p><b>CONCLUSION</b>The mutation of mt3243 A to G in the mitochondrial tRNA(Leu(UUR)) gene is an important cause of diabetes in Shanghai, Jiangsu and Zhejiang Province of China. Mitochondrial gene mutation diabetes (MDM) is clinically characterized by early onset, emaciation, maternal inheritance, sensorineural hearing loss, and lower islet beta cell function, and some have insulin resistance.</p>

Association of apelin genetic variants with type 2 diabetes and related clinical features in Chinese Hans / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Apelin is an adipokine that contributes to the pathogenesis of type 2 diabetes. The plasma levels of apelin increased in obese patients and diabetic subjects. This study aimed to investigate the effects of apelin genetic variants on type 2 diabetes and related quantitative traits.</p><p><b>METHODS</b>We selected three single nucleotide polymorphisms (SNPs) that could capture all common variants in APLN gene region and genotyped them in 1892 type 2 diabetic patients and 1808 normal glucose regulation controls. The clinical features related to glucose metabolism were measured in the controls. The comparison of allele and genotype distribution in the cases and controls were performed by using chi(2) tests. The association between SNPs and quantitative traits were analyzed using Wilcoxon's rank-sum test.</p><p><b>RESULTS</b>None of the SNPs or haplotypes showed evidence of association to type 2 diabetes. However, rs2235306 was nominally associated with fasting plasma glucose levels in the male subjects with normal glucose regulation ((4.93 +/- 0.03) vs (5.01 +/- 0.03) mmol/L, P = 0.04). No significant difference was observed between all three SNPs and other variables.</p><p><b>CONCLUSIONS</b>APLN SNP rs2235306 was associated with fasting plasma glucose levels in males. It suggests that APLN genetic variants may contribute to clinical features related to glucose metabolism in Chinese population.</p>

Study on the status of metabolic syndrome in familial type 2 diabetes pedigrees / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of metabolic syndrome (MS) and its components in type 2 diabetes mellitus pedigrees.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>(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-degree 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 in females for subjects aged below 60 and it was higher in females than in males for subjects aged over 60.</p><p><b>CONCLUSION</b>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.</p>

Intracellular retention of human melanocortin-4 receptor: a molecular mechanism underlying early-onset obesity in F261S pedigree of Chinese / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate how F261S mutation identified from Chinese obese patients affects the function of melanocortin 4 receptor (MC4R) and to analyze the obesity-related phenotypes in subjects carrying the F261S mutation.</p><p><b>METHODS</b>F261S mutant of MC4R was generated by site-directed mutagenesis. Plasmids encoding wild-type or F261S mutant of MC4R were transfected into HEK293 and COS-7 cells to examine their functional characteristics. Signaling properties of F261S MC4R were assessed by measuring intracellular cAMP levels in response to alpha-MSH stimulation. Cell surface expression of F261S MC4R was compared with that of wild-type MC4R. Clinical examinations were performed in subjects carrying F261S mutation and in non-mutated controls.</p><p><b>RESULTS</b>The alpha-MSH-stimulated reporter gene activity was significantly reduced in cells expressing F261S MC4R, with a maximal response equal to 57% of wild-type MC4R. The F261S mutation also led to a significant change in the Es50 value compared with the wild-type receptor (P<0.01). Immunofluorescent assay revealed a marked reduction in plasma membrane localization of the MC4R in cells expressing the F261S mutant receptor. The resting metabolic rate and fat composition of the mutant carriers were not significantly different from those of the non-mutated obese controls.</p><p><b>CONCLUSIONS</b>The decreased response to alpha-MSH due to the intracellular retention of MC4R may cause early-onset obesity in the F261S pedigree of Chinese.</p>

Relationship between the level of fasting plasma glucose and beta cell functions in Chinese with or without diabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Type 2 diabetes is a chronic disease characterized by a progressive loss of beta cell functions. However, the evaluation of beta cell functions is either expensive or inconvenient for clinical practice. We aimed to elucidate the association between the changes of insulin responsiveness and the fasting plasma glucose (FPG) during the development of diabetes.</p><p><b>METHODS</b>A total of 1192 Chinese individuals with normal blood glucose or hyperglycemia were enrolled for the analysis. The early insulinogenic index (DeltaI30/DeltaG30), the area under the curve of insulin (AUC-I), and homeostasis model assessment were applied to evaluate the early phase secretion, total insulin secretion, and insulin resistance respectively. Polynomial regression analysis was performed to estimate the fluctuation of beta cell functions.</p><p><b>RESULTS</b>The DeltaI30/DeltaG30 decreased much more rapidly than the AUC-I accompanying with the elevation of FPG. At the FPG of 110 mg/dl (a pre-diabetic stage), the DeltaI30/DeltaG30 lost 50% of its maximum while the AUC-I was still at a compensated normal level. The AUC-I exhibited abnormal and decreased gradually at the FPG of from 130 mg/dl to higher (overt diabetes), while the DeltaI30/DeltaG30 almost remained at 25% of its maximum value. When hyperglycemia continuously existed at > 180 mg/dl, both the DeltaI30/DeltaG30 and AUC-I were totally lost.</p><p><b>CONCLUSION</b>The increased fasting plasma glucose reflects progressive decompensation of beta cell functions, and could be used to guide the strategy of clinical treatments.</p>

Orthogonal factor analysis on metabolic syndrome / 中华流行病学杂志

To elucidate the principal of orthogonal factor analysis, using an example of factor analysis of metabolic syndrome. The basic structures and the fundamental concepts of orthogonal factor analysis were introduced and data involving 1877 women aged of 35-65 years, selected from a cross-sectional study, which was conducted in 1998 - 2001 in Shanghai, were included in this study. Factor analysis was carried out using principle components analysis with Varimax orthogonal rotation of the components of the metabolic syndrome. The different components of the metabolic syndrome were not linked closely with the other components and loaded on the six different factors,which mainly reflected by the variables of obesity, blood pressure, plasma glucose, plasma insulin, triglycerides and HDL-cholesterol respectively. Six major factors of the metabolic syndrome were uncorrelated with each other and explained 86% of the variance in the original data. The factor score and total factor score for the individual could be obtained according to the component score coefficient matrix. Although the components of the metabolic syndrome were related statistically, the finding of six factors suggested that the components of the metabolic syndrome did not show high degrees of intercorrelation. As a linear method of data reduction, the mode reduced a large set of measured intercorrelation variables into a smaller set of uncorrelated factors, which explained the majority of the variance in the original variables. Factor analysis was well suited for revealing underlying patterns or structure among variables showing high degrees of intercorrelation.

Serum lipid profile changes of the adults in Shanghai communities / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the adult lipid profile of Huayang community from 1998 to 2000 and Caoyang communities in 2001.</p><p><b>METHODS</b>Representative serum samples of 5628 adults (aged 20 - 95 years) were obtained in Huayang and Caoyang communities during 1998.9 and 2001.11. Standard epidemiology questionnaire, physical check-ups and serum lipids data were analyzed.</p><p><b>RESULTS</b>After standardization to Chinese census statistics of 2000, the age-and sex-standardized means of total cholesterol, HDL-C, LDL-C and triglycerides of the two communities (Huayang vs. Caoyang) were 5.01 mmol/L vs. 4.43 mmol/L, 1.28 mmol/L vs. 1.32 mmol/L, 3.37 mmol/L vs. 2.99 mmol/L, 1.97 mmol/L vs. 1.60 mmol/L respectively, and the age- and sex- standardized prevalence of dyslipidemia was 52.9% vs. 25.1%, and the prevalence for borderline dyslipidemia was 76.0% vs. 56.2%, respectively. The decreasing order of dyslipidemia prevalence of the two communities was: elevated TG, decreased HDL-C, elevated LDL-C and TC. The standardized proportions of optimal HDL-C level were only 15.7% and 16.1% in Huayang and Caoyang respectively which was much lower than these of TG, LDL and TC.</p><p><b>CONCLUSIONS</b>The standardized prevalence of adult dyslipidemia and borderline dyslipidemia in the two communities were high. Dyslipidemia of the two communities was TG and decreased.</p>

The genetic and clinical characteristics of transcription factor 1 gene mutations in Chinese diabetes / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the genetic and clinical features of mutations and sequence variations of the transcription factor 1 gene (TCF1, HNF-1A) in Chinese with familial early-onset and/or multiplex diabetes mellitus.</p><p><b>METHODS</b>All ten exons of the TCF1 gene were screened, including exon and intron junctions, by direct sequencing method in 341 unrelated Chinese subjects, including 80 healthy controls and 261 probands of early-onset and/or multiplex diabetes pedigrees.</p><p><b>RESULTS</b>Five mutations were found in all. Four of the 5 different TCF1 mutations were newly identified novel mutations(T82M, Q130H, G253G, P353fsdelACGGGCCTGGAGC), mean body mass index of mutation carriers was 21.9 kg/m (2), and insulin secretion was impaired in the mutation carriers. In this study, the maturity-onset diabetes of the young type III (MODY3) only accounted for 3% of Chinese early-onset diabetes. Moreover, eleven substitutions were identified in 261 probands. Of them, three variants IVS1-8 (G-->A), IVS1 -128 (T-->G ) and IVS2+21 (G-->A) were not observed in 80 healthy controls and one of them IVS1-8 (G-->A) was not reported previously and the two promoter variants co-segregated with diabetes.</p><p><b>CONCLUSION</b>TCF1 gene is not a common cause of early-onset and/or multiplex diabetes among Chinese patients.</p>

An analysis method to apply linkage disequilibrium maps to association study / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To apply linkage disequilibrium (LD) maps to associations studies with high throughput single nucleotide polymorphisms (SNPs).</p><p><b>METHODS</b>Seven hundred and fifty-four SNPs were genotyped in 160 Shanghai Chinese. LD maps were constructed in cases and controls separately. By comparing the decline of LD unit with distance between the two groups, disease susceptible loci were estimated. This method was compared with traditional analyses including LD analysis, single SNP and haplotype analyses.</p><p><b>RESULTS</b>The analysis of LD maps could detect the chromosome regions with different LD patterns between the cases and controls. The alleles and/or haplotypes frequencies of SNPs within the regions had significantly different distributions or trends of significantly different distributions.</p><p><b>CONCLUSION</b>This method may be applied to analyze the data from association studies with high throughput SNPs genotype information.</p>

Association of a common haplotype of hepatocyte nuclear factor 1alpha with type 2 diabetes in Chinese population / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To analyze the association of variants of hepatocyte nuclear factor-1alpha (HNF-1alpha) gene with type 2 diabetes in Chinese population.</p><p><b>METHODS</b>In 152 unrelated type 2 diabetes patients and 93 unrelated controls, eleven single nucleotide polymorphisms (SNPs) were identified and genotyped. Statistical analyses were performed to investigate whether these SNPs were associated with diabetes status in our samples.</p><p><b>RESULTS</b>In the individual SNP study, no SNP differed significantly in frequency between type 2 diabetes patients and controls. In the haplotype analysis, two haplotype blocks were identified. In haplotype block 1, no evidence was found between common HNF-1alpha haplotypes and type 2 diabetes. However, in haplotype block 2, a common haplotype GCGC formed by four tagging SNPs (tSNPs) was found to be associated with decreased risk of type 2 diabetes (odds ratio [OR] 0.6011, 95% confidence interval [CI] 0.4138-0.8732, P = 0.0073, empirical P = 0.0511, permutation test). A similar trend was also observed in the diplotype analysis, indicating that the increasing copy number of the haplotype GCGC was associated with the decreased frequency of diabetes (P = 0.0193).</p><p><b>CONCLUSION</b>The results of this study provide evidence that the haplotype of HNF-1alpha decreases the risk of type 2 diabetes in Chinese individuals.</p>

Relationship between adiponectin receptor 1 gene -3881T/C variant and glucose metabolism in the Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between adiponectin receptor 1 gene (ADIPOR1) single nucleotide polymorphism (SNP) and glucose metabolism and insulin resistance in the Chinese.</p><p><b>METHODS</b>The genotypes of -3881T/C of ADIPOR1 were determined through polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) in 664 Chinese in Shanghai. Among them, 370 were subjects with normal glucose tolerance and 294 were newly diagnosed diabetic patients without taking any drug. Phenotype measured were: height, weight to calculate body mass index; systolic blood pressure and diastolic blood pressure; plasma glucose level, serum insulin and C-peptide levels of blood obtained both at 0 and 120 minute during a standard 75-gram glucose oral glucose tolerance test. Insulin resistance and beta cell function were assessed by homeostasis model assessment (HOMA-IR and HOMA-B).</p><p><b>RESULTS</b>(1) The frequencies of two alleles did not differ between the type 2 diabetic patients and ones with normal glucose tolerance (P is 0.6749). (2) The frequency of C allele is significantly lower in type 2 diabetic patients with insulin resistance compare with those without insulin resistance (P is 0.0121). (3) In type 2 diabetic patients, the C allele carriers had a significantly lower diastolic blood pressure (P is 0.0466) and HOMA-IR (P is 0.0498). (4) In subjects with normal glucose tolerance, the C allele carriers had a significantly lower fasting plasma glucose (P is 0.0140).</p><p><b>CONCLUSION</b>These findings suggest that variant of ADIPOR1 plays a role in glucose metabolism and insulin resistance in the Chinese.</p>

Current studies on new parameters of metabolic syndrome / 中国医学科学院学报

The current definition of metabolic syndrome focuses on the individual accumulation of multiple cardiovascular risk factors. However, metabolic syndrome is often also constantly accompanied with abnormal body fat distribution, tissue insulin resistance, low-grade inflammation, and dysfunctional secretion and regulation of adipokines, which have become new highlights in the research of the pathogenesis and clinical indices of metabolic syndrome.

Characteristic of hypertensive subjects with metabolic syndrome and its components in communities / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the clinical characteristics of hypertensive subjects with metabolic syndrome and its components in communities.</p><p><b>METHODS</b>Totally 5628 subjects aged over 20 years were included. Measurement indicators included height, weight, waist circumference (W) , hip circumference, systolic pressure (SP) , diastolic pressure (DP) , total cholesterol ( TC) , triglyceride (TG) , high-density lipoprotein cholesterol (HDL-C) , low-density lipoprotein cholesterol (LDL-C) , fasting plasma glucose (FPG) , 2 h postprandial plasma glucose (2hPG) , fasting serum insulin (FIN) , and 2 h postprandial serum insulin (2hIN). Body mass index (BMI) , waist to hip ratio (WHR), and homeostatic model approach-insulin resistance index (HOMA-IR) were calculated. According to 1999 WHO definition of metabolic syndrome, these individuals were divided into 4 groups: non-metabolic disorder group, isolated hypertension group, hypertension with one component of metabolic syndrome group, hypertension with two components of metabolic syndrome group, and hypertension with three components of metabolic syndrome group.</p><p><b>RESULTS</b>Among subjects with hypertension, 15. 37% were patients with isolated hypertension, 32. 40% with one component of metabolic syndrome, 33. 36% with two components of metabolic syndrome, and 18. 87% with three components of metabolic syndrome. BMI, W, WHR, TC, TG, LDL-C, FPG, 2hPG, FIN, 2hIN and HOMA-IR in three groups (hypertension with one component of metabolic syndrome group, hypertension with two components of metabolic syndrome group, and hypertension with three components of metabolic syndrome group) significantly increased than those in isolated hypertension group (P < 0. 01 ). The hypertensive patients showed a higher insulin resistance, despite other metabolic disorders. Furthermore, the hypertensive patients with more components of metabolic syndrome showed a higher chance to get insulin resistance. Multiple stepwise regression analysis showed FPG, 2hPG, FIN, 2hIN, BMI, SP and TC were risk factors of HOMA-IR.</p><p><b>CONCLUSIONS</b>Patients with isolated hypertension are rare in community-based population. About 85% of hypertensive patients have more than one metabolic disorders, more than half of were metabolic syndrome. The percentage of total body fat, levels of plasma glucose, serum insulin, total cholesterol and systolic blood pressure are independent risk factors of insulin resistance.</p>

Identification of four novel mutations in the HNF-1A gene in Chinese early-onset and/or multiplex diabetes pedigrees / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mutations in the hepatocyte nuclear factor-1A gene cause the type 3 form of maturity-onset diabetes of the young (MODY3). This study was undertaken to determine mutations and sequence variations of the HNF-1A gene in Chinese with familial early-onset and/or multiplex diabetes mellitus.</p><p><b>METHODS</b>We screened all ten exons of the HNF-1A gene, including exon/intron junctions, by direct sequencing in 272 unrelated Chinese, including 80 healthy controls and 192 probands of early-onset and/or multiplex diabetes pedigrees.</p><p><b>RESULTS</b>In addition to one silent mutation of c.864 G > C [p.G288G] in exon4 at codon 288, which had been reported previously, a total of four novel mutations including two missense mutations (c.245C > T [p.T82M] and c. 390 G > T [p.Q130H]) and one frameshift mutation P353fsdelACGGGCCTGGAGC and one silent mutation c.759 G > T [p.G253G] were identified. Moreover, eleven substitutions were identified in 192 probands. Of these, three variants (-8 G > A, -128 T > G and IVS2 + 21 G > A) were not observed in 80 healthy controls and one of them (-8 G > A) was not reported previously and the two promoter variants co-segregated with diabetes. The genotype and allele frequencies of the other eight variants in the diabetic patients were not significantly different from those in the healthy controls. No significant relationships were observed between the eight variants of the HNF-1A gene and clinical variables (plasma glucose, insulin, C-peptide and fasting lipid profile).</p><p><b>CONCLUSION</b>The prevalence of structural mutations in the HNF-1A gene responsible for familial early-onset and/or multiplex diabetes appears to be rare among Chinese patients.</p>