Yuqian Bao

Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.

We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.

Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver disease patients and are correlated with hepatic triglyceride

BACKGROUND & AIMSnFibroblast growth factor 21 (FGF21), a hormone primarily secreted by the liver in response to peroxisome proliferator-activated receptor-α (PPARα) activation, has recently been shown to possess beneficial effects on lipid metabolism and hepatic steatosis in animal models. This study investigated the association of FGF21 with nonalcoholic fatty liver disease (NAFLD) in Chinese patients.nnnMETHODSnSerum FGF21 levels were determined by enzyme-linked immunosorbent assay (ELISA) in 224 NAFLD and 124 control subjects, and their association with parameters of adiposity, glucose, and lipid profiles and levels of liver injury markers was studied. Besides serum concentrations, the mRNA expression of FGF21 in the liver tissue was also quantified by real-time PCR in 17 subjects with different degrees of steatosis, and was correlated with the levels of intrahepatic lipid. The protein levels of FGF21 were determined by quantitative ELISA.nnnRESULTSnSerum FGF21 levels in patients with NAFLD (402.38 pg/ml [242.03, 618.25]) were significantly higher than those in control subjects (198.62 pg/ml [134.96, 412.62]) (p<0.01). In human liver tissues, FGF21 mRNA expression increased with the degree of steatosis. Both FGF21 mRNA expression and serum FGF21 concentrations were positively correlated with intrahepatic triglyceride (TG) having r = 0.692 and r = 0.662, respectively, at p<0.01. Furthermore, the increased expression of FGF21 was accompanied by elevated protein levels in liver tissues.nnnCONCLUSIONSnThese results support the role of FGF21 as a key regulator of hepatic lipid metabolism in humans, and suggest that serum FGF21 can be potentially used as a biomarker for NAFLD.

Variants from GIPR, TCF7L2, DGKB, MADD, CRY2, GLIS3, PROX1, SLC30A8 and IGF1 are associated with glucose metabolism in the Chinese.

BACKGROUNDnRecent meta-analysis of genome-wide association studies in European descent samples identified novel loci influencing glucose and insulin related traits. In the current study, we aimed to evaluate the association between these loci and traits related to glucose metabolism in the Chinese.nnnMETHODS/PRINCIPAL FINDINGSnWe genotyped seventeen single nucleotide polymorphisms (SNPs) from fifteen loci including GIPR, ADCY5, TCF7L2, VPS13C, DGKB, MADD, ADRA2A, FADS1, CRY2, SLC2A2, GLIS3, PROX1, C2CD4B, SLC30A8 and IGF1 in 6,822 Shanghai Chinese Hans comprising 3,410 type 2 diabetic patients and 3,412 normal glucose regulation subjects. MADD rs7944584 showed strong association to type 2 diabetes (pu200a=u200a3.5×10(-6), empirical pu200a=u200a0.0002) which was not observed in the European descent populations. SNPs from GIPR, TCF7L2, CRY2, GLIS3 and SLC30A8 were also associated with type 2 diabetes (pu200a=u200a0.0487∼2.0×10(-8)). Further adjusting age, gender and BMI as confounders found PROX1 rs340874 was associated with type 2 diabetes (pu200a=u200a0.0391). SNPs from DGKB, MADD and SLC30A8 were associated with fasting glucose while PROX1 rs340874 was significantly associated with OGTT 2-h glucose (pu200a=u200a0.0392∼0.0014, adjusted for age, gender and BMI), the glucose-raising allele also showed association to lower insulin secretion. IGF1 rs35767 showed significant association to both fasting and 2-h insulin levels as well as insulin secretion and sensitivity indices (pu200a=u200a0.0160∼0.0035, adjusted for age, gender and BMI).nnnCONCLUSIONS/SIGNIFICANCEnOur results indicated that SNPs from GIPR, TCF7L2, DGKB, MADD, CRY2, GLIS3, PROX1, SLC30A8 and IGF1 were associated with traits related to glucose metabolism in the Chinese population.

Effects of GCK, GCKR, G6PC2 and MTNR1B Variants on Glucose Metabolism and Insulin Secretion

Background Single nucleotide polymorphisms (SNPs) from GCK, GCKR, G6PC2 and MTNR1B were found to modulate the fasting glucose levels. The current study aimed to replicate this association in the Chinese population and further analyze their effects on biphasic insulin secretion. Methods/Principal Findings SNPs from GCK, GCKR, G6PC2 and MTNR1B were genotyped in the Shanghai Chinese, including 3,410 type 2 diabetes patients and 3,412 controls. The controls were extensively phenotyped for the traits related to glucose metabolism and insulin secretion. We replicated the association between GCK rs1799884, G6PC2 rs16856187 and MTNR1B rs10830963 and fasting glucose in our samples (pu200a=u200a0.0003∼2.0×10−8). GCK rs1799884 and G6PC2 rs16856187 showed association to HOMA-β, insulinogenic index and both first- and second-phases insulin secretion (pu200a=u200a0.0030∼0.0396). MTNR1B rs10830963 was associated to HOMA-β, insulinogenic index and first-phase insulin secretion (pu200a=u200a0.0102∼0.0426), but not second-phase insulin secretion (pu200a=u200a0.9933). Combined effect analyses showed individuals carrying more risk allele for high fasting glucose tended to have a higher glucose levels at both fasting and 2 h during OGTTs (pu200a=u200a1.7×10−13 and 0.0009, respectively), as well as lower HOMA-β, insulinogenic index and both first- and second-phases insulin secretion (pu200a=u200a0.0321∼1.1×10−7). Conclusions/Significance We showed that SNPs from GCK, G6PC2 and MTNR1B modulated the fasting glucose levels in the normoglycaemic population while SNPs from G6PC2 and GCKR was associated with type 2 diabetes. Moreover, we found GCK and G6PC2 genetic variants were associated to both first- and second-phases insulin secretion while MTNR1B genetic variant was associated with first-phase insulin secretion, but not second-phase insulin secretion.

Serum levels of osteocalcin are inversely associated with the metabolic syndrome and the severity of coronary artery disease in Chinese men

Objectiveu2002 Osteocalcin is a bone‐derived protein and has been shown to play an important role in regulating glucose and fat metabolism. We therefore investigated the association of serum levels of osteocalcin with the metabolic syndrome (MS) and coronary atherosclerosis in Chinese men.

Serum Levels of Adipocyte Fatty Acid-Binding Protein Are Associated with the Severity of Coronary Artery Disease in Chinese Women

BACKGROUNDnAdipocyte fatty acid-binding protein (A-FABP) has been described as a novel adipokine, playing an important role in the development of metabolic syndrome, type 2 diabetes and atherosclerosis. In this study, we investigated the relationship between serum levels of A-FABP and the presence and severity of coronary artery disease (CAD) in Chinese subjects.nnnMETHODOLOGY/PRINCIPAL FINDINGSnCirculating A-FABP level was determined by ELISA in 341 Chinese subjects (221 men, 120 women) who underwent coronary angiography. A-FABP levels in patients with CAD were significantly higher compared with non-CAD subjects (P = 0.029 in men; P = 0.031 in women). Serum A-FABP increased significantly in multi-vessel diseased patients than in non-CAD subjects (P = 0.011 in men, P = 0.004 in women), and showed an independent correlation with coronary atherosclerosis index (standardized β = 0.173, P = 0.025). In multiple logistic regression analysis, serum A-FABP was an independent risk factor for CAD in women (OR = 5.637, 95%CI: 1.299-24.457, P = 0.021). In addition, amino terminal pro-brain natriuretic peptide (NT-proBNP) was demonstrated to be positively and independently correlated with A-FABP (standardized β = 0.135, P = 0.027).nnnCONCLUSIONS/SIGNIFICANCEnSerum A-FABP is closely associated with the presence and severity of CAD in Chinese women.

Preliminary Evaluation of the Sural Nerve Using 22-MHz Ultrasound: A New Approach for Evaluation of Diabetic Cutaneous Neuropathy

Background The application of 22-MHz high-frequency ultrasound allows for visualization of the inner part of the sural nerve. The aim of this study was to evaluate the morphological changes of sural nerves in patients with type 2 diabetes mellitus using ultrasound. Materials and Methods The thickness/width (T/W) ratio, the cross-sectional area (CSA) of the sural nerves and the maximum thickness (MT) of the nerve fascicles were measured in 100 patients with type 2 diabetes mellitus and 50 healthy volunteers using 22-MHz ultrasound. Receiver operating characteristic (ROC) curves were plotted to determine the optimal cut-off values as well as the sensitivities and specificities. All parameters were significantly different between the subject and control groups. The ROC curves demonstrated that the MT was the most predictive of diabetic cutaneous neuropathy, with an optimal cut-off value of 0.365 mm that yielded a sensitivity of 90.3% and a specificity of 87.7%. Conclusions The results of this study suggest that 22-MHz ultrasound may be a valuable tool for evaluating diabetic cutaneous nerve neuropathy.

Prevalence and risk factors of albuminuria and chronic kidney disease in Chinese population with type 2 diabetes and impaired glucose regulation: Shanghai diabetic complications study (SHDCS)

BACKGROUNDnDiabetes is a major risk factor for the development of kidney disease. We aimed to determine the prevalence of albuminuria and chronic kidney disease (CKD) in Chinese subjects with diabetes and pre-diabetes and the risk factors for kidney disease.nnnMETHODSnAn urban community-based sample of 3714 adults in Shanghai was classified into normal glucose tolerance (NGT), impaired glucose regulation (IGR) and diabetes. The estimated glomerular filtration rate (eGFR) and the urinary albumin-to-creatinine ratio (ACR) were applied to designate renal function and albuminuria, respectively. Binary logistic regression was performed to analyse the contribution of risk factors to CKD. Polynominal regression was used to determine the trends of eGFR with the increment of ACR.nnnRESULTSnThe prevalence of microalbuminuria, macroalbuminuria and CKD in subjects with diabetes was 22.8%, 3.4% and 29.6%, respectively, which was significantly higher than that in non-diabetes subjects. After adjustment for age, the odds ratio of hypertension for albuminuria and renal insufficiency (eGFR <60 mL/min/1.73 m(2,) stages 3-5 of CKD) were 1.23 (P = 0.000) and 2.55 (P = 0.000). Diabetes and cardiovascular disease (CVD) both increased the risk for albuminuria significantly, with the odds ratio of 1.22 (P = 0.04) and 1.36 (P = 0.006), respectively. Diabetes and CVD were not independent risk factor for renal insufficiency. Although the worsening trends of eGFR are similar in diabetes and IGR subjects, IGR was not a significant risk factor for albuminuria and renal insufficiency.nnnCONCLUSIONnScreening for albuminuria and eGFR is highly recommended for older patients with diabetes, hypertension and CVD to prevent end-stage kidney disease.

Determination of diabetic retinopathy prevalence and associated risk factors in Chinese diabetic and pre-diabetic subjects: Shanghai diabetic complications study

The prevalence of diabetic retinopathy is not well studied in the Chinese pre‐diabetic population, also known as impaired glucose regulation. Hence, we investigated the prevalence of and risk factors associated with retinopathy in diabetic and pre‐diabetic subjects from Chinese communities.

Comparison of body mass index with body fat percentage in the evaluation of obesity in Chinese.

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