Kun-san Xiang’s research while affiliated with Shanghai University and other places

Non-alcoholic fatty liver disease (NAFLD) is becoming a major public health hazard in China. The present study aimed to estimate the prevalence of NAFLD, NAFLD with abnormal serum alanine aminotransferase (ALT) levels, and determine the potential associations of ALT levels with the components of metabolic syndrome (MetS) in the absence or presence of NAFLD in Chinese adults. A population-based cross-sectional survey was conducted with 2226 participants. Physical examinations, laboratory tests and hepatic ultrasounds were performed. Individuals were further stratified into higher or lower ALT subgroups with the upper quartiles of ALT in this population. The MetS was identified according to the criteria of the Chinese Joint Committee for Developing Chinese Guidelines (JCDCG). The standardized prevalence of NAFLD was 23.3% (NAFLD with abnormal ALT levels, 3.1%), 26.5% (NAFLD with abnormal ALT levels, 5.1%) in males, and 19.7% (NAFLD with abnormal ALT levels, 0.9%) in females. Multivariate logistic analysis revealed that higher ALT was significantly associated with elevated triglyceride (TG) in the non-NAFLD participants, independent of age, smoking status, drinking status, and other MetS-related measures with odds ratios (95% confidence intervals) of 3.4 (1.6-7.1) and 2.3 (1.4-3.7) in males and females, respectively. On the other hand, the higher ALT was statistically associated with elevated TG and hyperglycemia in the NAFLD cases with odds ratios of 2.2 to 2.5 (P<0.05). The prevalence of NAFLD has become epidemic in Shanghai adults. NAFLD combined with ALT levels may be used to identify the individuals at the different risk levels of metabolic disorders.

1. The aim of the present study was to assess the validity of glycated albumin (GA) and fasting plasma glucose (FPG) as a screening tool for the early detection of diabetes in Chinese subjects. 2. A total of 1971 outpatient subjects underwent a 75 g oral glucose tolerance test (OGTT) and GA measurement. The receiver operating characteristic curve (ROC) was plotted to examine the sensitivity, specificity, and positive and negative predictive values of GA and FPG in detecting undiagnosed diabetes at the different cut-off levels. 3. The prevalence of impaired glucose regulation and diabetes was 27.40% and 38.30%. For these diabetic individuals, 4.64% had isolated fasting hyperglycemia, 50.86% had isolated postprandial hyperglycemia and 44.50% had both. Using ROC analysis, a GA of 17.1% gave an optimal sensitivity of 76.82% (95% confidence interval: 73.64–79.79%) and specificity of 76.89% (74.42–79.23%) for the diagnosis of diabetes. Likewise, a FPG of 6.1 mmol/L gave an optimal sensitivity of 80.93% (77.94–83.67%) and specificity of 85.94% (83.86–87.84%). If subjects met both criteria, they were regarded as having diabetes; the positive predictive value of the combined criteria, FPG ≥ 6.1 mmol/L and GA ≥ 17.1%, was relatively high (84.79% (81.62–87.60%)), and this would have avoided 76% of the OGTT in our survey. 4. In conclusion, a GA value of 17.1%, an optimal cut-off in Chinese subjects, identified a high proportion of potential diabetic individuals. Simultaneous measurement of FPG and GA would enhance the sensitivity of diabetes screening in our population and avoid 76% of OGTT.

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. 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. 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. 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.

To evaluate the present Chinese body mass index (BMI) criteria with body fat percentage (BF%) in determining obesity in Chinese population. 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. 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%. 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).

To investigate a potential association between SNP rs10494366 in the neural nitric oxide synthase adaptor protein (NOS1AP) and efficacy of repaglinide (an insulin secretagogue) in newly diagnosed Shanghai Chinese type 2 diabetes patients. A total of 104 newly diagnosed type 2 diabetes patients (69 men, 35 women) were recruited and treated with repaglinide for 24 weeks. Anthropometric measurements, clinical laboratory tests were obtained at baseline and after 24-week treatment. Genotyping was performed by sequencing. The baseline value of BMI, HOMA-IR, HOMA-B, and fasting insulin level were significantly different between GG, GT, and TT genotypes (P=0.024, 0.030, 0.005, and 0.007, respectively). Carriers of TT genotype were in significant insulin resistance at baseline. After 24-week repaglinide monotherapy, the Delta value of fasting insulin (P=0.019) and HOMA-IR (P=0.011) were significantly different. TT carriers had the least insulin resistance after treatment. The mixed model analysis showed that the variation had an interaction effect with repaglinide treatment only on HOMA-IR (P=0.013). A common variant in rs10494366 is associated with repaglinide monotherapy efficacy on insulin resistance in newly diagnosed Shanghai Chinese type 2 diabetes patients.

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. 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. 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. 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.

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. 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. 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. 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.

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. 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. 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). 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.

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. 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. 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. 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.

To investigate the prevalence, clinical features of latent autoimmune diabetes in adults (LADA) from phenotypic type 2 diabetic patients and the relationship between LADA and metabolic syndrome (MS). Sera from 1711 phenotypic type 2 diabetic patients were screened for glutamic acid decarboxylase antibody (GAD-Ab) and protein tyrosine phosphatase antibody (IA2-Ab) through radioligand assay. The prevalence of LADA and its relation with clinical features were analyzed. (1) The prevalence of LADA in phenotypic type 2 diabetic patients was 6.7% (115/1711), the positive frequency of GAD-Ab and IA2-Ab was 6.0% and 2.4% respectively. (2) The prevalence of LADA from phenotypic type 2 diabetic patients with a duration of diabetes less than 1 year which was much higher than that of patients with a duration over 1 year (10.4% vs 5.9%, P < 0.01). (3) The prevalence of LADA was higher in patients with younger age at onset, lower body mass index and lower level of postprandial C peptide and without diabetes family history. (4) 51.3% of LADA patients were suffered from at least one kind of metabolic disorders besides hyperglycemia, 21.7% of them were with MS. The prevalence from high to low of those metabolic disorders were as follows: hypertension, dyslipidemia, overweight/obesity. (1) 6.7% of phenotypic type 2 diabetic patients were LADA, of whom early diagnosis of diabetic type should be made to guide clinical therapies. (2) More than 1/5 patients with MS were found in LADA patients, indicating an overall screening and intervention of metabolic disorder factors is important in LADA patients.