ABSTRACT
Objective To investigate the gender difference of the plasma lactic acid(LA) levels in type 2 diabetics with normal renal and hepatic function, and the effect of metformin on LA levels in the difference gender. Methods A total of 1 021 type 2 diabetic inpatients with normal renal and hepatic functions were collected,including metformin treatment group (213 males and 210 females) and metformin non-treatment group (299 males and 299 females). LA was measured with enzyme-electrode assay. Fasting plasma glucose ( FPG), creatinine ( Cr), and alanine aminotransferase ( ALT) levels were determined. Results LA level in metformin treatment group was significantly higher than that in metformin non-treatment group [ (1.32±0.53 vs 1.14±0.49) mmol/L,P<0.01],and 61 cases had hyperlactacidemia but no lactic acidosis was found. Spearman correlation analysis showed that LA level was positively associated with gender,metformin, and body mass index( BMI) apart from Cr and ALT( P<0.01). Multivariate logistic regression analysis showed that gender,Cr,ALT,and metformin were independent correlated factors of hyperlactacidemia. LA levels in females were higher than those of males in the whole group and two groups treated or not treated with metformin (all P<0. 05 ). LA levels in females were higher compared to male in Cr and ALT subgroups,as well as age subgroups,especially with age younger than 45 years old (P=0.021). Conclusions There is gender difference of lactate level in diabetic patients,and the effect of metformin on the plasma lactate levels of different gender is varied. The plasma LA level in females,especially those approaching menopause,are prone to hoist.
ABSTRACT
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.
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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.
ABSTRACT
Objective To study the impact of single nucleotide polymorphism 43 (UCSNP43) of calpain 10 gene (CAPN 10) at NIDDM1 locus, chromosome 2q37.3 on glucose intolerance status and its intermediate traits. Methods The studied population consisted of 320 Chinese subjects in Shanghai 〔normal glucose tolerance (NGT) 148, impaired glucose tolerance (IGT) 44 and type 2 diabetes (T2DM) 128〕. Plasma glucose, insulin, C peptide and free fatty acid levels were measured during fasting and 30, 60, 120 and 180 min after oral 75 g glucose load. The tissue insulin sensitivity and islet beta cell insulin secretion were assessed by HOMA formulae and the ratio of the increment of insulin and glucose levels at 30 min. The CAPN 10 UCSNP43 was genotyped by DNA direct sequencing. Results (1) The frequencies of GG, GA and AA genotypes of CAPN 10 UCSNP 43 were 0.80, 0.18 and 0.02 respectively. The G allele frequency was 0.89, which was statistically significant higher than those in Caucasians, Mexican Americans and Pima Indians (all P