ObjeclJve To definine the corresponding value to glycated albumin(GA)for a specific target of HbAlc,and to elvaluate the relationship between GA and HbA1c.Methods From Oct.2006 TO Apr.2009, 2 532 subjects were enrolled who accepted oral glucose tolerance test(OGtt)in out-patient department,including 898 with normal glucose regulation,695 with impaired glucose regulation,and 939 with newly-diagnosed diabetes.GA was measured with liquid enzymatic method.HbA1c was measured with high performance liquid chromatography method.The plasma glucose was measured at fasting,0.5 h,1 h,2 h,and 3h after glucose load.The correlation among GA,HbA1c and the other parameters monitored was analyzed.Results (1)The levels of HbA1c and GA in 2 532 subjects were(6.3±1.1)% and(17.9±4.5)%.The ratio of GA/HbA1c was 2.85±0.51.(2)HbAlc and GA were positively correlated with fasting,0.5 h,1 h,2 h and 3 h plasma glucose(r was in 0.567-0.776,atl P<0.01).(3)GA was significantly correlated with HbA1c(r=0.701,P<0.01).Linear regression analysis,using GA and HbA1c summarized by patient(n=2 532),produced a relationship of GA=2.871×HbA1c-0.112.The change in GA per increase of 1% HbA1c was 2.87%.When HbA1c level was 6.5%,the expected value of GA was 18.5%.The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy with GA≤18.5% to predict HbA1c≤6.5% were 82.32%,72.49%,86.48%.65.73%,and 79.19%,respectively.When HbA1c level was 7.0%,the expected value of GA was 20.O%.When HbA1c level was 7.5%.the expected value of GA was 21.4%.Conclusions We initially establish the corresponding value to GA for a specific target of HbA1c and provide the basis for clinical application.

To investigate the relationship between serum glutamic acid decarboxylase antibody (GAD-Ab)titer and the first-phase insulin release (1PH)in newly-diagnosed type 2 diabetic patients. 1053 newly-diagnosed type 2 diabetic patients were divided into 3 groups, including 71 individuals with GAD-Ab≥1 U/ml (positive group), 171 individuals with GAD-Ab ranging from 0 to 1 U/ml (negative-1 group), and 811 individuals with GAD-Ab=0 (negative-2 group). IPH was evaluated by arginine stimulation test. In the patients of negative-2, negative-1, and positive groups, the respective values of 1 PH were subsequently decreased significantly (P< 0. 01) , and the detection rates of the decreased insulin secretion were 74. 85%, 87. 13%, and 100%, respectively. Stepwise regression analysis indicated that disease duration, GAD-Ab titer, HbA_1C, and body mass index were the major independent contributing factors. The titer of GAD-Ab has an important impact on 1PH defect in type 2 diabetic patient. Detection of GAD-Ab not only provides an evidence for clinical type, but would also be helpful in determining the islet β-cell function.

Objective To study the relationship between plasma creatinine and lactic acid levels in type 2 diabetic patients with normal renal function, and the effect of mefformiu administration on plasma lactic acid. Methods Blood samples were collected from 723 type 2 diabetic inpatients(275 cases treated with mefformin as treatment group and 448 without mefformin as control group). Plasma lactic acid was measured with enzyme-electrode assay. The fasting plasma glucose, fasting insulin, creatinine (Cr) , alanine aminotransferase (ALT), and HbA1C levels were also determined. Results (1) The lactic acid level in treatment group was significantly higher than that in control group [(1.33±0.57 vs 1.17±0.47) mmol/L, P<0.01] and so was the incidence of hyperlactacidemia (9.45% vs 4.91%, P<0.01). No lactic acidosis was found in all patients. (2) The correlation analysis showed that Cr, blood urea nitrogen, ALT and body mass index (BMI) were positively correlated with lactic acid in control group, and the positive correlation between Cr and lactic acid still existed (r= 0.345, P<0.01) after adjustment for ALT and BMI. (3) After being divided by 20 μmol/L Cr in control group, lactic acid levels in subgroup increased with the Cr levels, especially when Cr was over 90 μmol/L. The Cr cutpoint for predicting lactatemia was 95.35 μmol/L. Conclusion It is safe to administrate metformin in type 2 diabetic patients with normal renal function, along with low risk of lactic acidemia. The incidence of lactic acidemia may increase when plasma Cr level reaches 95.35 μmol/L,

Objective To screen the variation in NeuroD1 gene and to study its function in vitro and its clinical phenotypes and genetic characteristics in Chinese early-onset type 2 diabetic probands. Methods PCR-direct sequencing of NeuroD1 gene was performed in 85 early-onset type 2 diabetic probands, 95 late-onset type 2 diabetics with strong diabetic history and 87 non-diabetic control subjects. Distributions of the identified variation were calculated and compared among the three groups. Expression vectors with mouse NeuroD1 (mND1)cDNA wild type or mutant type and reporter vectors with human insulin promotor-linked luciferase were constructed. Then the above vectors were co-transfected into rat INS-1 cells. Relative luciferase activities were measured to compare transcriptional activities of insulin gene between WT and MT. Results S159P (T→C), a new mutation was identified in a proband, which was co-segregated with diabetes in 4 carriers from the paternal side. The functional study showed that the S159P mutant exhibited a 25% reduction in transcriptional activity of insulin gene as compared with the wild type. A45T (G→A), a common variation was identified. The AA + GA genotypic frequencies were markedly increased in early-onset type 2 diabetic probands as compared with late-onset type 2 diabetic probands and non-diabetic control subjects (P=0.006 and P=0.014, respectively). Conclusion The novel S159P mutation in the NeuroDl gene seems to contribute to the development of diabetes in the Chinese early-onset type 2 diabetic family. The A45T variation may increase susceptibility to or be in disequilibrium with early-onset type 2 diabetes mellitus in Chinese population. In addition, the A45T variation may affect the onset pattern of type 2 diabetes mellitns, such as early-onset but not late-onset type 2 diabetes mellitus.

Objective To investigate the effect of solute cartier organic anion transporter family, member 1B1 (SLCOIBI) gene variants on the response to therapy with repaglinide in type 2 diabetes. Methods 100 newly-diagnosed type 2 diabetic patients were treated with repaglinide during a course of 48 weeks. Anthropometrie parameters and indices related to glucose metabolism were measured periodically. Genotypes of SLCO1B1 D130N and V174A were detected by PCR-restriction fragment length polymorphism (RFLP) and sequencing respectively. Results Eighty-nine patients accomplished the 48-week follow-up visits. D130N variant in SLCO1B1 gene was associated with repaglinide treatment, DD genotype had better HbA1C lowering effect than N allele carrier [△HbA1C: (-2.29±0.23) % vs (-1.49±0.21)%, P<0.05]. No association was detected between D130N and the other effects of repaglinide on glucose metabolism related phenotypes. Conclusion D130N variant in SLCO1B1 gene is associated with the response to repaglinide treatment in patients with type 2 diabetes. DD homozygotes had a better effect than N allele carriers.

Objective To compare the differences of metabolic syndrome (MS) prevalence by using four working definitions and their relationship with obesity-related indicators in first-degree relatives of type 2 diabetes mellitus pedigrees. Methods Totally, 2 372 first-degree relatives 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 obesity of four definitions, as defined by National Cholesterol Education Program Adult Treatment Panel Ⅲ (ATPⅢ) in 2005, International Diabetes Federation (IDF) in 2005,Chinese Diabetes Society (CDS) in 2004 aml Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults (JCDCG) in 2007,were analyzed. Results (1)The prevalence rates of MS were 45.40% ,38.74% ,25.08% and 39.29% aecording to four definitions respectively. The prevalence rates of MS were higher in females than in males by using ATPⅢ and IDF definitions (both P<0. 01). (2)The common comhinations of metabolic abnormality was dyslipidemia, hypertension, obesity and hyperglycemia by using four definitions,except in females by using CDS definition. (3)The prevalence rates of obesity were 58.18% ,58.18% ,33.90% and 42.96% acconling to the four definitions respectively. The prevalence rates of MS in obese subjects were 66.59% ,66.59% ,54.85% and 68.99% according to four definitions respectively. (4) Applying the cutoff point for abdominal obesity according to ATPⅢ, IDF and JCDCG definitions, the prevalence rates of abdominal obesity in subjects with body mass index (BMI) <25 kg/m2 were respectively 28.58% and 16.78%, being higher in females than in males(38.90% vs 15.02% ,21.01% vs 11.22% ,both P<0. 01). Conclusion (1)There is significant familial aggregation of MS and obesity,and the first-degree relatives of type 2 diabetic patients are high risk populations. (2) Waist circumference rather than BMI taken as a discriminating component of obesity in MS seems to be clinically more helpful to the early identification and prevention of MS.

Objective To evaluate the clinical significance of glycated albumin (GA), a parameter in reflecting recent glycemic control, in patients with impaired glucose regulation (IGR) and newly diagnosed diabetes mellitus. Methods From January to June 2007, 516 subjects who accepted oral glucose tolerance test (OGTT) in out-patient department were randomly enrolled, including 130 with normal glucose regulation (NGR), 154 with IGR and 232 with diabetes mellitus. The fasting plasma glucose (FPG), 0.5 h plasma glucose (PG), 1hPG, 2hPG, 3hPG after glucose loading, HbA1c and GA were measured in each subject. The correlation between GA and the other parameters were analyzed. Results There were significant differences in the values of GA among NGR, IGR and diabetes mellitus groups (all P < 0.01), but no difference in the values of HbA1c between NGR group and IGR group (P > 0.05). GA was positively correlated with HbA1c (r = 0.75, P < 0.01). Stepwise regression analysis showed that FPG, 2hPG and body mass index were the major independent contributing factors. Conclusion The combination of plasma glucose with GA measurement may be helpful in evaluating the status of glucose metabolism.

Objective To explore the possible association of single nucleotide polymorphism (SNP) rs3738435 of muscarinic acetylcholine receptor subtype M3 gene (cholinergic receptor, muscarinic 3, CHRM3) with risk of type 2 diabetes mellitus (DM) and metabolic disturbance. Methods The genotypes of T-149C variant of CHRM3 gene were determined by PCR-RFLP in 573 Chinese individuals in Shanghai, including 220 newly-diagnosed type 2 DM patients without taking any drug and 353 subjects with normal glucose tolerance (NGT). In the subjects, height and weight were measured for body mass index(BMI), waist, hip and femoral circumstances for waist-to-hip ratio (WHR) and waist-to-femur ratio (WFR), and serum lipid level including total cholesterol, triglyceride, high-density and low-density lipoprotein cholesterol, blood pressure, plasma glucose levels both at 0 and 120 minute during oral 75 g glucose tolerance test (OGTT) were also determined. Results (1) There was no statistical difference in the gene frequency between groups of type 2 DM and NGT. (2) In the group of type 2 DM, significant differences were observed between TT genotype carriers and TC+CC genotypes carriers for BMI, with an obvious increase in TY genotype carriers [(26.99±3.59vs25.34±3.48)kg/m2, P=0.001]. (3) In the subgroup of type 2 DM with BMI≥25 kg/m2, total cholesterol was higher in TT genotypes than in TC+CC genotypes[(5.75±1.26vs5.27±1.14)mmol/L, P=0.030], so was the low-density lipoprotein cholesterol. Conclusion The genetic variation T-149C in the CHRM3 gene seems to attribute to weight regulation and lipid metabolism of patients with type 2 diabetes mellitus in Chinese population.

OBJECTIVETo 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.

METHODSAbdominal 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.

RESULTS1) 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.

CONCLUSIONBMI, WC, WHR can all predict abdominal visceral obesity, with WC the best.

Adipose Tissue ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Body Constitution ; Body Mass Index ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Obesity ; metabolism ; physiopathology ; Predictive Value of Tests ; Sensitivity and Specificity

OBJECTIVETo 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.

METHODSPolymerase 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).

CONCLUSIONAlthough 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 ; metabolism ; Adult ; Aged ; Alleles ; Body Constitution ; Body Mass Index ; Carrier Proteins ; genetics ; China ; Cholesterol ; metabolism ; Cholesterol, HDL ; metabolism ; Cholesterol, LDL ; metabolism ; Diabetes Mellitus, Type 2 ; genetics ; metabolism ; Female ; Gene Frequency ; Genotype ; Humans ; Ion Channels ; Lipid Metabolism ; Male ; Middle Aged ; Mitochondrial Proteins ; Point Mutation ; Regression Analysis ; Triglycerides ; metabolism ; Uncoupling Protein 3