Xuhong Hou

Serum osteocalcin concentrations in relation to glucose and lipid metabolism in Chinese individuals.

OBJECTIVES Osteocalcin, a bone-derived protein, has recently been reported to affect energy metabolism. We investigated the relationship between serum osteocalcin and parameters of adiposity, glucose tolerance, and lipid profile in Chinese subjects. METHODS Serum osteocalcin was measured by electrochemiluminescence immunoassay in 254 men (128 with newly diagnosed type 2 diabetes mellitus (T2DM) and 126 with normal glucose tolerance (NGT)), 66 premenopausal women (33 with T2DM and 33 with NGT) as well as 180 postmenopausal women (92 with T2DM and 88 with NGT). Their associations with parameters of adiposity, glucose tolerance, and lipid profile were examined. RESULTS Serum osteocalcin concentrations in diabetic patients were significantly lower than those in NGT subjects after adjusted for age, gender, and body mass index (P=0.003). Postmenopausal women had higher osteocalcin concentrations than premenopausal women and men (both P<0.001). Multiple stepwise regression analysis showed that age, %fat, high-density lipoprotein cholesterol, fasting plasma glucose, and fasting serum insulin were independently associated with osteocalcin in men (P<0.05). Age and HbA1c were independently correlated with osteocalcin in postmenopausal women. Besides age and HbA1c, serum triglyceride was also an independent factor influencing osteocalcin in premenopausal women. In addition, osteocalcin was also positively associated with homeostasis model assessment of beta-cell function. Furthermore, multiple logistic regression analysis demonstrated that osteocalcin was independently associated with T2DM. CONCLUSIONS Serum osteocalcin was closely associated with not only fat and glucose metabolism but also with lipid metabolism.

PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population.

Background Recent advance in genetic studies added the confirmed susceptible loci for type 2 diabetes to eighteen. In this study, we attempt to analyze the independent and joint effect of variants from these loci on type 2 diabetes and clinical phenotypes related to glucose metabolism. Methods/Principal Findings Twenty-one single nucleotide polymorphisms (SNPs) from fourteen loci were successfully genotyped in 1,849 subjects with type 2 diabetes and 1,785 subjects with normal glucose regulation. We analyzed the allele and genotype distribution between the cases and controls of these SNPs as well as the joint effects of the susceptible loci on type 2 diabetes risk. The associations between SNPs and type 2 diabetes were examined by logistic regression. The associations between SNPs and quantitative traits were examined by linear regression. The discriminative accuracy of the prediction models was assessed by area under the receiver operating characteristic curves. We confirmed the effects of SNPs from PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 on risk for type 2 diabetes, with odds ratios ranging from 1.114 to 1.406 (P value range from 0.0335 to 1.37E-12). But no significant association was detected between SNPs from WFS1, FTO, JAZF1, TSPAN8-LGR5, THADA, ADAMTS9, NOTCH2-ADAM30 and type 2 diabetes. Analyses on the quantitative traits in the control subjects showed that THADA SNP rs7578597 was association with 2-h insulin during oral glucose tolerance tests (P = 0.0005, empirical P = 0.0090). The joint effect analysis of SNPs from eleven loci showed the individual carrying more risk alleles had a significantly higher risk for type 2 diabetes. And the type 2 diabetes patients with more risk allele tended to have earlier diagnostic ages (P = 0.0006). Conclusions/Significance The current study confirmed the association between PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and type 2 diabetes. These type 2 diabetes risk loci contributed to the disease additively.

Glycated haemoglobin A1c for diagnosing diabetes in Chinese population: cross sectional epidemiological survey

Objectives To evaluate haemoglobin A1c (HbA1c) in diagnosing diabetes and identify the optimal HbA1c threshold to be used in Chinese adults. Design Multistage stratified cross sectional epidemiological survey. Setting Shanghai, China, 2007-8. Participants 4886 Chinese adults over 20 years of age with no history of diabetes. Main outcome measures Performance of HbA1c at increasing thresholds for diagnosing diabetes. Results The area under the receiver operating characteristics curve for detecting undiagnosed diabetes was 0.856 (95% confidence interval 0.828 to 0.883) for HbA1c alone and 0.920 (0.900 to 0.941) for fasting plasma glucose alone. Very high specificity (96.1%, 95% confidence interval 95.5% to 96.7%) was achieved at an HbA1c threshold of 6.3% (2 SD above the normal mean). Moreover, the corresponding sensitivity was 62.8% (57.1% to 68.3%), which was equivalent to that of a fasting plasma glucose threshold of 7.0 mmol/l (57.5%, 51.7% to 63.1%) in detecting undiagnosed diabetes. In participants at high risk of diabetes, the HbA1c threshold of 6.3% showed significantly higher sensitivity (66.9%, 61.0% to 72.5%) than both fasting plasma glucose ≥7.0 mmol/l (54.4%, 48.3% to 60.4%) and HbA1c ≥6.5% (53.7%, 47.6% to 59.7%) (P<0.01). Conclusions An HbA1c threshold of 6.3% was highly specific for detecting undiagnosed diabetes in Chinese adults and had sensitivity similar to that of using a fasting plasma glucose threshold of 7.0 mmol/l. This optimal HbA1c threshold may be suitable as a diagnostic criterion for diabetes in Chinese adults when fasting plasma glucose and oral glucose tolerance tests are not available.

Impact of waist circumference and body mass index on risk of cardiometabolic disorder and cardiovascular disease in Chinese adults: a national diabetes and metabolic disorders survey.

Background We updated the prevalence of obesity and evaluated the clinical utility of separate and combined waist circumference (WC) or body mass index (BMI) category increments in identifying cardiometabolic disorder (CMD) and cardiovascular disease (CVD) risk in Chinese adults. Methods and Findings 46,024 participants aged ≥20 years, a nationally representative sample surveyed in 2007–2008, were included in this analysis. Taking the cutoffs recommended by the Chinese Joint Committee for Developing Chinese Guidelines (JCDCG) and the Working Group on Obesity in China (WGOC) into account, the participants were divided into four WC and four BMI groups in 0.5-SD increments around the mean, and 16 cross-tabulated combination groups of WC and BMI. 27.1%, 31.4%, and 12.2% of Chinese adults are centrally obese, overweight, or obese according to JCDCG and WGOC criteria. After adjustment for confounders, after a 1-SD increment, WC is associated with a 1.7-fold or 2.2-fold greater risk of having DM or DM plus dyslipidemia than BMI, while BMI was associated with a 2.3-fold or 1.7-fold higher hypertension or hypertension plus dyslipidemia risk than WC. The combination of WC and BMI categories had stronger association with CMD risk, i.e., the adjusted ORs (95% CI) of having DM, hypertension, and dyslipidemia for the combined and separate highest WC and BMI categories were 2.19 (1.96–2.44) vs 1.88 (1.67–2.12) and 1.12 (0.99–1.26); 5.70 (5.24–6.19) vs 1.51 (1.39–1.65) and 1.69 (1.57–1.82); and 3.73 (3.42–4.07) vs 2.16 (1.98–2.35) and 1.33 (1.25–1.40), respectively. The combination of WC and BMI categories was more likely to identify individuals with lower WC and lower BMI at CVD risk, even after the effects of CMD were controlled (all P<0.05). Conclusion Central obesity, overweight, and obesity are epidemic in Chinese adults. The combination of WC and BMI measures is superior to the separate indices in identifying CMD and CVD risk.

Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4.

Aims/hypothesisMost genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.MethodsWe performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.ResultsWe identified CDKN2A/B and four novel type 2 diabetes association signals with p < 1 × 10−5 from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (pmeta = 2.6 × 10−8; OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (pmeta = 2.3 × 10−10) and a population of European descent (p = 8.6 × 10−3). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians.Conclusions/interpretationOur study identifies rs10229583 near PAX4 as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.

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

BACKGROUND Recent 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. METHODS/PRINCIPAL FINDINGS We 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 (p = 3.5×10(-6), empirical p = 0.0002) which was not observed in the European descent populations. SNPs from GIPR, TCF7L2, CRY2, GLIS3 and SLC30A8 were also associated with type 2 diabetes (p = 0.0487∼2.0×10(-8)). Further adjusting age, gender and BMI as confounders found PROX1 rs340874 was associated with type 2 diabetes (p = 0.0391). SNPs from DGKB, MADD and SLC30A8 were associated with fasting glucose while PROX1 rs340874 was significantly associated with OGTT 2-h glucose (p = 0.0392∼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 (p = 0.0160∼0.0035, adjusted for age, gender and BMI). CONCLUSIONS/SIGNIFICANCE Our 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.

Risk factors for overweight and obesity, and changes in body mass index of Chinese adults in Shanghai

BackgroundOver the past two decades, the prevalence of overweight or obesity has increased in China. The aims of this study were to firstly assess the baseline prevelences and the risk factors for overweight and obesity, and secondly to detect the changes of body mass index (BMI) over a follow-up period in Chinese adults in Shanghai.MethodsThe data set of a population-based longitudinal study was analyzed. Anthropometric and biochemical data were collected for 5364 subjects (aged 25–95 years) during a period of 1998–2001. Among those individuals, 3032 subjects were interviewed and reexamined at the second survey from 2003 to 2004. Then the standardized prevalences for overweight and obesity were calculated using baseline data; the possible contributing factors of overweight and obesity were detected using binary logistic regression analysis; and the changes of BMI were evaluated after an average of 3.6-year follow-up period.Results(1) According to the WHO standard and the Chinese standard, the sex- and age-standardized prevalences were 27.5% and 32.4% for overweight, and 3.7% and 9.1% for obesity, respectively. (2) The risks of overweight and obesity differed among different age groups. Family history of obesity increased the risk of overweight and obesity by about 1.2-fold for both genders. Current male smokers had a lower risk of overweight and obesity (OR = 0.76, p < 0.05) than nonsmokers. In contrast, current male drinkers had a higher risk of overweight and obesity (OR = 1.42, p < 0.05) than nondrinkers. Compared with low-educated women, medium- and high- educated women were at lower risk of overweight and obesity, and the corresponding ORs (95% CIs) were 0.64 (0.52–0.79) and 0.50(0.36–0.68), respectively. (3) The annual changes of BMI means ranged from an increase of 0.1 kg/m2 to a decrease of 0.2 kg/m2 (by genders and age groups). Meanwhile, the BMI increase was statistically significant in the 35–44 years age group, and the BMI decrease was significant above 65 years for both genders.ConclusionThis study showed high prevalence of overweight and obesity in Shanghai metropolis populations. The risk factors of overweight and obesity were multifactorial and gender specific. After 3.6 years, BMI means changed slightly, BMI increased mainly in middle-aged individuals and decreased in old individuals.

High serum level of fibroblast growth factor 21 is an independent predictor of non-alcoholic fatty liver disease: A 3-year prospective study in china.

BACKGROUND & AIMS Fibroblast growth factor 21 (FGF21), a hormone predominantly secreted by the liver, has been shown to be positively associated with the severity of non-alcoholic fatty liver disease (NAFLD) in cross-sectional studies. We investigated the prospective association of FGF21 with NAFLD development in a 3-year prospective study involving a population-based cohort comprising 808 Chinese subjects. METHODS Serum FGF21 levels at baseline and follow-up were measured using an enzyme-linked immunosorbent assay. Independent predictors of NAFLD development were identified using multiple logistic regressions. The predicting accuracy of the models was evaluated using area under the receiver-operating characteristic (ROC) curves (AUCs). RESULTS In subjects who had progressed to NAFLD, the baseline FGF21 concentration (319.12 pg/ml [172.65, 518.78]) was significantly higher than that in subjects who did not develop NAFLD (199.10 pg/ml [123.56, 322.80]) (p <0.001). At follow-up, significant increase of FGF21 level was observed in those subjects who developed NAFLD (p <0.05). Baseline FGF21 was an independent predictor of NAFLD (OR: 7.102 [95% CI 2.488-20.270]; p <0.001), together with body mass index (BMI) (OR: 1.489 [95% CI 1.310-1.691]; p <0.001). The ROC-AUC was 0.816 (95% CI 0.766-0.867) for the FGF21 Model, which was calculated with FGF21 and BMI. FGF21 Model <0.13 can be used to rule out (sensitivity=85.71%, negative likelihood ratio=0.23) and ≥0.30 can be rule in (specificity=86.34%, positive likelihood ratio=3.66) ultrasonography-diagnosed NAFLD after 3 years. CONCLUSIONS High serum FGF21 concentration was an independent predictor of NAFLD in humans. The FGF21 Model and its cut-offs may be useful for early diagnosis and intervention of NAFLD.

Non-alcoholic fatty liver disease's prevalence and impact on alanine aminotransferase associated with metabolic syndrome in the Chinese

Background and Aim:  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.

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)

BACKGROUND Diabetes 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. METHODS An 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. RESULTS The 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. CONCLUSION Screening for albuminuria and eGFR is highly recommended for older patients with diabetes, hypertension and CVD to prevent end-stage kidney disease.