Identification of circulating sphingosine kinase-related metabolites for prediction of type 2 diabetes.

BACKGROUND: Sphingosine Kinase (SphK) that catalyzes sphingosine (Sph) to sphingosine 1-phosphate (S1P), plays a key role in both sphingolipid metabolism and cellular signaling. While SphK has been implicated in type 2 diabetes mellitus (T2DM), it is unexplored in humans. Herein, we investigated whether circulating SphK-related metabolites are associated with T2DM incidence in an established prospective cohort. METHODS: Levels of SphK-related sphingolipid metabolites, including Sph, S1P, dihydrosphingosine (dhSph) and dihydro-S1P (dhS1P) in serum were measured by targeted-lipidomic analyses. By accessing to an established prospective cohort that involves a total of 2486 non-diabetic adults at baseline, 100 subjects who developed T2DM after a mean follow-up of 4.2-years, along with 100 control subjects matched strictly with age, sex, BMI and fasting glucose, were randomly enrolled for the present study. RESULTS: Comparison with the control group, medians of serum dhS1P and dhS1P/dhSph ratio at baseline were elevated significantly prior to the onset of T2DM. Each SD increment of dhS1P and dhS1P/dhSph ratio was associated with 53.5% and 54.1% increased risk of incident diabetes, respectively. The predictive effect of circulating dhS1P and dhS1P/dhSph ratio on T2DM incidence was independent of conventional risk factors in multivariate regression models. Furthermore, combination of serum dhS1P and dhS1P/dhSph ratio with conventional clinical indices significantly improved the accuracy of T2DM prediction (AUROC, 0.726), especially for normoglycemic subjects (AUROC, 0.859). CONCLUSION: Circulating levels of dhS1P and dhS1P/dhSph ratio are strongly associated with increased risk of T2DM, and could serve as a useful biomarker for prediction of incident T2DM in normoglycemic populations.

The PNPLA3 rs738409 C>G variant interacts with changes in body weight over time to aggravate liver steatosis, but reduces the risk of incident type 2 diabetes.

AIMS/HYPOTHESIS: The rs738409 C>G variant of the patatin-like phospholipase domain containing 3 gene (PNPLA3) increases the risk of non-alcoholic fatty liver disease (NAFLD) with no predisposition for insulin resistance. In this study, we aimed to investigate the influence of PNPLA3 polymorphisms on liver fat content (LFC) and glucose metabolic variables, and the associations between these, during the natural course of body weight changes in a Chinese adult cohort. METHODS: The LFC, measured using a quantitative ultrasound method, was prospectively monitored in 2189 middle-aged and elderly adults from the Shanghai Changfeng Study, together with changes in body weight and metabolic variables. General linear models were used to detect interactive effects between the PNPLA3 rs738409 genotype and 4 year changes in body weight on liver steatosis and glucose metabolism. RESULTS: The PNPLA3 homozygous GG genotype dissociated the changes in the LFC and OGTT 2 h post-load blood glucose (PBG) in relation to 4 year changes in body weight. PNPLA3 GG genotype carriers showed greater increases in the LFC and serum alanine aminotransferase (ALT) but lower PBG elevation and incident diabetes than PNPLA3 wild-type (CC) genotype carriers exhibiting the same degree of body weight increase. The interactions between the PNPLA3 genotype and changes in body weight on the LFC (false discovery rate [FDR]-adjusted pinteraction = 0.044) and ALT (FDR-adjusted pinteraction = 0.044) were significant. Subgroup analyses showed that the effect of the PNPLA3 GG genotype on changes in the LFC and PBG was only observed in metabolically unhealthy participants with insulin resistance or abdominal obesity. CONCLUSIONS/INTERPRETATION: The PNPLA3 GG genotype interacted with changes in body weight to aggravate liver steatosis but reduced the risk of incident type 2 diabetes in metabolically unhealthy participants.

Association of visceral adiposity and its longitudinal increase with the risk of diabetes in Chinese adults: A prospective cohort study.

OBJECTIVE: A Chinese visceral adiposity index (CVAI) was recently established to estimate the visceral fat area in Chinese adults. This study aimed to investigate the risk of incident prediabetes and diabetes in relation to visceral adiposity calculated by CVAI. METHODS: A total of 2558 subjects with normal plasma glucose levels from the Shanghai Changfeng Study were enrolled in a prospective cohort study. The independent associations of basal visceral fat area by CVAI and its longitudinal change with incident prediabetes and diabetes were identified using Cox regression analyses. RESULTS: During an average of 4.4 years of follow-up, 546 (21.3%) and 99 (3.9%) of 2558 nondiabetic subjects developed prediabetes and diabetes, respectively. Visceral fat area by CVAI and its longitudinal increase were independently associated with incident prediabetes and diabetes in Chinese adults. In a multivariable-adjusted regression model, CVAI, as well as its annual change, was the strongest independent predictor of incident prediabetes (HR, 1.383 [1.162-1.647]) and diabetes (HR, 1.607 [1.092-2.364]) compared with other estimates of obesity (BMI and waist circumference). Receiver operating characteristic curve analyses showed that CVAI had better performance than BMI and waist circumference for the prediction of prediabetes and diabetes in Chinese adults. CONCLUSIONS: Visceral adiposity plays a pivotal role in the pathogenesis of diabetes, and the visceral adiposity estimated by CVAI is superior to the traditional estimates of obesity for the prediction of incident prediabetes and diabetes in Chinese adults.

The association of liver fat content and serum alanine aminotransferase with bone mineral density in middle-aged and elderly Chinese men and postmenopausal women.

BACKGROUND: Recent studies have linked non-alcoholic fatty liver disease (NAFLD) to a reduced bone mineral density (BMD). We aimed to detect the quantitative association of liver fat content (LFC) and serum alanine aminotransferase (ALT) with BMD in a middle-aged and elderly Chinese population. METHODS: The lumbar spine, hip and whole body BMDs were measured using dual-energy x-ray absorptiometry (Lunar iDXA, GE Healthcare) in 1659 Chinese (755 men and 1028 postmenopausal women) from Shanghai Changfeng community. Liver fat content was quantified via an ultrasound quantitative method. Multivariate linear regression analyses were carried out to determine the independent association of LFC and serum ALT with BMD and bone metabolic biomarkers. We also attempted to investigate the synergistic association between LFC and ALT as risk factors for bone mineral loss in Chinese. RESULTS: Subjects with higher LFC had significantly lower BMD at all skeletal sites. Univariate correlation analysis showed that both LFC and ALT were inversely associated with BMD at the spine (r = -0.116, P < 0.001 and r = -0.102, P = 0.005), hip (r = -0.095, P = 0.014 and r = -0.075, P = 0.041) and whole body sites (r = -0.134, P < 0.001 and r = -0.164, P < 0.001) in men. After confounders were controlled for, LFC and ALT remained associated with BMD and bone formation biomarkers in men, but not postmenopausal women. When both NAFLD and elevation of ALT were present, there was a significant synergistic worsening of the BMDs at all bone sites. CONCLUSIONS: Liver fat content and serum ALT were inversely correlated with BMD in middle-aged and elderly men. The underlying mechanism might relate to a reduction in osteoblast activity. Elevation of the hepatotoxic biomarker ALT may indicate high risk for osteoporosis in patients with NAFLD.

Glycated haemoglobin in diagnosis of diabetes mellitus and pre-diabetes among middle-aged and elderly population: Shanghai Changfeng study.

OBJECTIVE: To investigate the optimal glycated haemoglobin (HbA1c) cut off points and evaluate the impact of HbA1c on diabetes and pre-diabetes in middle-aged and elderly population. METHODS: Subjects were recruited from Shanghai Changfeng Study. A total of 1973 community-based participants (age ⋝45) without known diabetes underwent oral glucose tolerance test (OGTT) by using a 75-g oral glucose load and HbA1c was measured by using high performance liquid chromatography (HPLC). Subjects were classified as normal glucose tolerance (NGT), pre-diabetes(impaired glucose regulation, IGR) and new diagnosed diabetes (NDD) per 1999 WHO criteria. Two tests are compared with receiver operating characteristic curve (ROC). RESULTS: Among 1973 subjects, 271 (13.7%) were diagnosed as NDD and 474 (24.0%) as IGR by using OGTT. HbA1c was 5.7%±0.7% in this population. Use of 6.5% as the HbA1C cutoff point has sensitivity of 38.7% and specificity of 98.5%. We recommend 6.0% as a better cutoff value for diagnosis of diabetes in this population (AUC 0.829, 95% CI 0.798-0.860, P<0.001) with its sensitivity and specificity as 66.1% and 86.8%. For IGR, the results showed low sensitivity (44.9%) and specificity (66.7%) with an AUC of 0.571 for HbA1c when 5.8% was used as the cutoff point. Participants detected with HbA1c⋝6.0% were associated with nearly the same metabolic characteristics, including body mass index (BMI), blood pressure, lipid profile and urine albumin-creatinine ratio (uACR) compared with diabetic subjects detected by OGTT. CONCLUSION: The optimum HbA1c cutoff point for diabetes in our study population was lower than ADA criteria, and HbA1c may not be used to identify IGR.

Renal function-dependent association of serum uric acid with metabolic syndrome and hepatic fat content in a middle-aged and elderly Chinese population.

The effect of uric acid (UA) on the pathogenesis of metabolic disorders is highly dependent on its physicochemical properties, and hyperuricaemia associated with different conditions may have different clinical meanings. The aim of the present study was to investigate the association of serum UA levels with metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) in a middle-aged and elderly population with normal and impaired renal function. The cross-sectional study was performed on 1141 participants (426 men, 715 women; mean age 62 years) enrolled from the Shanghai Changfeng community. Each participant underwent a standard interview, with anthropometric and laboratory measurements. Hepatic fat content (HFC) was determined by a newly established quantitative ultrasound method. Univariate correlation analysis showed that serum UA was associated with all components of metabolic syndrome and HFC (r = 0.193, P < 0.001), especially in participants with a normal estimated glomerular filtration rate (eGFR; r = 0.255, P < 0.001). Logistic regression analysis demonstrated an independent association of serum UA with metabolic syndrome and NAFLD in participants with normal renal function, but not in those with eGFR < 90 mL/min per 1.73 m(2) . Furthermore, multivariate linear analysis showed that UA levels were independently associated with HFC (P = 0.003), but only in participants with normal eGFR. Elevated serum UA is independently associated with metabolic syndrome and NAFLD in patients with normal renal excretory function. However, in those with renal insufficiency, hyperuricaemia has no association with metabolic disorders.

Image enhancement of color fundus photographs for age-related macular degeneration: the Shanghai Changfeng Study.

AIM: To develop and evaluate a new fundus image optimization software based on red, green, blue channels (RGB) for the evaluation of age-related macular degeneration (AMD) in the Chinese population. METHODS: Fundus images that were diagnosed as AMD from the Shanghai Changfeng Study database were analyzed to develop a standardized optimization procedure. Image brightness, contrast, and color balance were measured. Differences between central lesion area and normal retinal area under different image brightness, contrast, and color balance were observed. The optimal optimization parameters were determined based on the visual system to avoid image distortion. A paired-sample diagnostic test was used to evaluate the enhancement software. Fundus optical coherence tomography (OCT) was used as the gold standard. Diagnostic performances were compared between original images and optimized images using McNemar's test. RESULTS: A fundus image optimization procedure was developed using 86 fundus images of 74 subjects diagnosed with AMD. By observing gray-scale images, choroid can be best displayed in red channel and retina in green channel was found. There was limited information in blue channel. Totally 104 participants were included in the paired sample diagnostic test to assess the performance of the optimization software. After the image enhancement, sensitivity increased from 74% to 88% (P=0.008), specificity decreased slightly from 88% to 84% (P=0.500), and Youden index increased by 0.11. CONCLUSION: The standardized image optimization software increases diagnostic sensitivity and may help ophthalmologists in AMD diagnosis and screening.

Elevation of liver enzymes within the normal limits and metabolic syndrome.

1. Metabolic syndrome is frequently associated with elevated liver enzymes. However, the current 'normal' limits for liver enzymes often fail to identify patients with metabolic syndrome and the associated non-alcoholic fatty liver disease (NAFLD). 2. In the present study, 1503 participants, aged between 18 and 95 years, were recruited from the physical examination centre of Shanghai Zhongshan Hospital and Shanghai Changfeng Community Health Centre. The association between liver enzymes within the 'normal' range and metabolic syndrome was investigated and optimal cut-off values for liver enzymes in metabolic syndrome were determined. We further compared the diagnostic performance of the new cut-off values for liver enzymes in metabolic syndrome and NAFLD with the traditional 'normal' range for liver enzymes. 3. Serum liver enzymes within the traditional 'normal' limits, especially alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT), were correlated with most of components of the metabolic syndrome, as determined by Spearman's partial correlation analysis. Logistic regression analysis revealed that within the 'normal' range of liver enzymes, the frequency of metabolic syndrome was significantly increased in the higher quintile for ALT and GGT compared with the lowest quintile. Receiver operating characteristic curve analysis revealed that the optimal cut-off values for ALT, aspartate aminotransferase and GGT to identify metabolic syndrome were 26, 25 and 29 U/L, respectively, in men and 20, 23 and 21 U/L, respectively, in women. These values were much more effective in detecting patients with potential metabolic syndrome and NAFLD than the traditional cut-off values. 4. A slight elevation of liver enzymes within the 'normal' limits, especially ALT and GGT, indicates the presence of metabolic syndrome and NAFLD. Revision of the current normal limits for liver enzymes is advisable so that patients with potential metabolic disorders can be identified.

Prediction of Metabolic Disorders Using NMR-Based Metabolomics: The Shanghai Changfeng Study.

A metabolically healthy status, whether obese or not, is a transient stage with the potential to develop into metabolic disorders during the course of life. We investigated the incidence of metabolic disorders in 1078 metabolically healthy Chinese adults from the Shanghai Changfeng Study and looked for metabolites that discriminated the participants who would develop metabolic disorders in the future. Participants were divided into metabolically healthy overweight/obesity (MHO) and metabolically healthy normal weight (MHNW) groups according to their body mass index (BMI) and metabolic status. Their serum metabolomic profile was measured using a 1H nuclear magnetic resonance spectrometer (1H-NMR). The prevalence of diabetes, hypertriglyceridemia, hypercholesterolemia and metabolic syndrome was similar between the MHNW and MHO participants at baseline. After a median of 4.2 years of follow-up, more MHO participants became metabolically unhealthy than MHNW participants. However, a subgroup of MHO participants who remained metabolically healthy (MHO → MHO) had a similar prevalence of metabolic disorders as the MHNW participants at the follow-up examination, despite a significant reduction in their serum concentrations of high-density lipoprotein (HDL) and an elevation in valine, leucine, alanine and tyrosine. Further correlation analysis indicated that serum intermediate-density lipoprotein (IDL) and very low-density lipoprotein cholesterol (VLDL-CH) might be involved in the transition from metabolically healthy to unhealthy status and could be valuable to identify the MHNW and MHO with increased metabolic risks.

Skeletal muscle loss is associated with diabetes in middle-aged and older Chinese men without non-alcoholic fatty liver disease.

BACKGROUND: Skeletal muscle, a key insulin target organ, has been reported to be associated with diabetes mellitus (DM). Compared to non-diabetic patients, diabetic patients have decreased muscle mass and a higher prevalence of sarcopenia, and patients with sarcopenia may be at increased risk of developing diabetes. In individuals with nonalcoholic fatty liver disease (NAFLD), sarcopenia is associated with the severity of fibrosis and steatosis. Previous studies have demonstrated that NAFLD is strongly associated with DM and sarcopenia. AIM: To determine the relationship between skeletal muscle mass and DM in Chinese middle-aged and elderly men, and whether the association is affected by NAFLD. METHODS: Skeletal muscle mass was calculated as appendicular skeletal muscle mass (ASM) in kg/body weight × 100%. Liver fat content (LFC) was measured using a quantitative ultrasound method. RESULTS: As the ASM decreased, fasting blood glucose (FBG), 2-h postprandial blood glucose (2hBG), and LFC increased in both genders, as did the prevalence of DM and NAFLD. Spearman analysis showed that the ASM was negatively correlated with the FBG, 2hBG, and LFC. Stepwise logistic regression analysis showed that after adjustments, the ASM quartile was negatively associated with the presence of DM in males, but not in females. Subgroup analysis showed that the ASM quartiles remained negatively correlated with the presence of DM in the non-NAFLD population (including males and females), but no correlation was found between ASM quartiles and the presence of DM in the NAFLD population. When stratified by LFC quartiles, ASM was negatively correlated with the presence of DM in the first and second LFC quartiles in males. CONCLUSION: Skeletal muscle mass loss was shown to be associated with the presence of DM in males, but not in females; NAFLD weakens this association. The results suggested that the stratified management of diabetes mellitus should be considered according to skeletal muscle mass and NAFLD.

Sarcopenia, sarcopenic overweight/obesity and risk of cardiovascular disease and cardiac arrhythmia: A cross-sectional study.

BACKGROUND: Sarcopenia is an age-dependent skeletal muscle disorder that is common in patients with heart failure. The current study aimed to investigate the associations of sarcopenia with carotid atherosclerosis, cardiovascular disease and cardiac arrhythmia in a middle-aged and elderly population without clinical heart failure. METHODS: A total of 2432 participants (992 men and 1440 women) from Shanghai Changfeng Study were included for analysis. The degree of sarcopenia was measured using height-adjusted appendicular skeletal muscle mass (ASM/height2). Carotid plaques were detected by carotid artery ultrasonography, and myocardial ischemia, infarction and cardiac arrhythmia were diagnosed based on electrocardiogram, past history and clinical manifestations. RESULTS: Sarcopenia was associated with higher prevalence of carotid atherosclerosis (26.4% vs 20.4%, P = 0.027), myocardial infarction (4.0% vs 1.1%, P = 0.001), and premature ventricular contraction (4.0% vs 2.0%, P = 0.034) in the participants with normal body weight, and higher prevalence of carotid atherosclerosis (45.0% vs 31.2%, P = 0.016), myocardial infarction (10.0% vs 4.3%, P = 0.020) and atrial fibrillation (7.5% vs 1.3%, P < 0.001) in those with overweight/obese status. After adjustment for age, gender, cigarette smoking, alcohol drinking, menopausal status in women and other metabolic and inflammatory confounding factors, sarcopenia was independently associated with the risk of myocardial infarction in the whole population, and the risk of atrial fibrillation in the overweight/obese participants (all P < 0.05). Compared with nonsarcopenic lean participants, the risk of myocardial infarction was gradually increased in sarcopenic lean (OR 3.08 [1.28-7.45], P = 0.012) and sarcopenic overweight/obese participants (OR 4.07 [1.31-12.62], P = 0.015). For the atrial fibrillation, the participants with either sarcopenia or overweight/obesity alone showed no higher risk. However, concomitant sarcopenia and overweight/obesity was associated with approximately 5-fold risk of atrial fibrillation (OR 5.68 [1.34-24.12], P = 0.019) after multiple adjustment. CONCLUSION: Sarcopenia is associated with myocardial infarction and atrial fibrillation in middle-aged and elderly adults without clinical heart failure.

The PNPLA3 rs738409 C>G variant influences the association between low skeletal muscle mass and NAFLD: the Shanghai Changfeng Study.

BACKGROUND: Age-related skeletal muscle loss and patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphisms are both associated with increased liver steatosis and fibrosis in the absence of obesity. AIM: To investigate the influence of PNPLA3 polymorphism on the relationship between skeletal muscle loss and non-alcoholic fatty liver disease (NAFLD). METHODS: Liver fat content was measured using a quantitative ultrasound method, and liver fibrosis was assessed by NAFLD fibrosis, BARD and FIB-4 scores in 3969 Chinese adults. The degree of sarcopenia was measured by weight-adjusted appendicular skeletal muscle mass (ASM% = appendicular skeletal muscle mass(kg)/body weight(kg)  100%). RESULTS: The NAFLD proportion increased from 19.9% to 41.2% in men and 26.3% to 42.3% in women with decreasing ASM% quartiles (P < 0.001). Low ASM% was inversely associated with NAFLD in PNPLA3 CC (odds ratio [OR]: men, 0.735 [0.610-0.885] and women, 0.812 [0.718-0.918], both P = 0.001) and CG (OR: men, 0.673 [0.573-0.790] and women, 0.798 [0.713-0.893], both P < 0.001) but not GG genotype carriers. The association remained significant after adjustment for age, cigarette smoking, fat mass, interaction between fat mass and ASM%, obesity, diabetes and all components of metabolic syndrome. Subgroup analyses found that PNPLA3 GG gene variant did not increase the risk for NAFLD in individuals with low ASM% regardless of obesity status. Low ASM% also increased risk for liver fibrosis (all P < 0.05), which became insignificant after multiple adjustments. CONCLUSIONS: Low ASM% is associated with NAFLD and liver fibrosis. Dissociation of sarcopenia and NAFLD was found in PNPLA3 GG genotype carriers. A stratification based on PNPLA3 genotypes might facilitate personalised treatment for NAFLD.

Serum folic acid levels are associated with the presence and severity of liver steatosis in Chinese adults.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a common and strong risk factor for cardiovascular disease and hepatocellular carcinoma. The rapid acceleration of the increase in NAFLD prevalence has exceeded the trends observed for obesity, and has been driven by multiple factors. The aim of this study was to investigate the correlation between the serum levels of folic acid, the endogenous source of methyl groups for DNA methylation, and NAFLD in Chinese adults. METHODS: The correlations between the serum folic acid levels and NAFLD were investigated in two independent cohorts of 70 subjects who underwent a liver biopsy and 130 subjects with varying liver fat contents, as measured using proton magnetic resonance spectroscopy (1H-MRS). Independent correlations between serum folic acid levels and liver steatosis grades were detected using a multivariate ordinal regression analysis. The diagnostic performances of serum folic acid levels alone and in combination with existing NAFLD prediction scores were compared with those of traditional NAFLD prediction parameters using receiver operating characteristic (ROC) curve analyses. RESULTS: Serum folic acid concentrations were inversely correlated with liver histological steatosis grades (ρ = -0.371, P < 0.001) and the 1H-MRS-measured liver fat content (r = -0.199, P = 0.038). According to the multivariate ordinal regression analysis, serum folic acid levels were inversely correlated with liver steatosis grades (OR 0.739 [0.594-0.918], P = 0.006) independent of age, gender, BMI, components of metabolic syndrome and the serum TC, LDL-c and HOMA-IR levels. The AUROC of serum folic acid for the diagnosis of NAFLD was 0.75 (0.65-0.83), and the addition of serum folic acid to NAFLD prediction scores significantly improved the diagnostic prediction of NAFLD (AUROC = 0.88 [0.81-0.94]). CONCLUSION: Low serum folic acid levels were identified as an independent risk factor for NAFLD in the Chinese population. The addition of the serum folic acid levels to the current existing NAFLD prediction scores significantly improved the prediction of NAFLD.

Influence of Ethnicity on the Accuracy of Non-Invasive Scores Predicting Non-Alcoholic Fatty Liver Disease.

OBJECTIVES: Presence of non-alcoholic fatty liver disease (NAFLD) can predict risks for diabetes, cardiovascular disease and advanced liver disease in the general population. We aimed to establish a non-invasive score for prediction of NAFLD in Han Chinese, the largest ethnic group in the world, and detect whether ethnicity influences the accuracy of such a score. METHODS: Liver fat content (LFAT) was measured by quantitative ultrasound in 3548 subjects in the Shanghai Changfeng Community and a Chinese score was created using multivariate logistic regression analyses. This new score was internally validated in Chinese and externally in Finns. Its diagnostic performance was compared to the NAFLD liver fat score, fatty liver index (FLI) and hepatic steatosis index (HSI) developed in Finns, Italians and Koreans. We also analyzed how obesity related to LFAT measured by 1H-MRS in 79 Finns and 118 Chinese with type 2 diabetes (T2D). RESULTS: The metabolic syndrome and T2D, fasting serum insulin, body mass index (BMI) and AST/ALT ratio were independent predictors of NAFLD in Chinese. The AUROC in the Chinese validation cohort was 0.76 (0.73-0.78) and in Finns 0.73 (0.68-0.78) (p<0.0001). 43%, 27%, 32% and 42% of Chinese had NAFLD when determined by the Chinese score, NAFLD liver fat score (p<0.001 vs. Chinese score), FLI (p<0.001) and HSI (NS). For any given BMI and waist circumference, the Chinese had a markedly higher LFAT than the Finns. CONCLUSION: The predictors of NAFLD in Han Chinese are as in Europids but the Chinese have more LFAT for any given degree of obesity than Europids. Ethnicity needs to be considered when NAFLD is predicted using risk scores.

A indicator of visceral adipose dysfunction to evaluate metabolic health in adult Chinese.

Visceral adipose dysfunction is a major cause of metabolic disorders. However, there is lack of a clinical index for prediction of visceral fat dysfunction in Asians. The present study aims to establish a visceral adiposity index for evaluation of metabolic health status in Chinese, the largest Asian ethnic group. 485 subjects were recruited from Lianqian Community, Xiamen and received abdominal computed tomography(CT) for visceral fat area. A Chinese visceral adiposity index (CVAI) was created using multivariate linear regression analyses, and was further validated in 6495 subjects recruited from Changfeng Community, Shanghai. CVAI was well associated with visceral obesity (r = 0.68, P < 0.001) and HOMA-IR (r = 0.60, P < 0.001). The AUROCs were 0.89(0.88-0.90), 0.72(0.71-0.73), 0.69(0.68-0.71) and 0.67(0.65-0.68) for determination of metabolic syndrome, hypertension, diabetes and prediabetes, respectively. CVAI was more valuable compared to BMI and waist circumference in evaluation of metabolic risks (all P < 0.001), even in subjects with metabolically unhealthy normal weight (MUNW) and metabolically healthy obese/overweight (MHO). This study demonstrates that CVAI is a reliable and applicable index for evaluation of visceral fat dysfunction in Chinese. It might be used to evaluate metabolic health status in Asians.

Assessment of liver fat content using quantitative ultrasonography to evaluate risks for metabolic diseases.

OBJECTIVE: The ultrasound quantitative method for liver fat content (LFC) is a recent established method for non-invasive assessment of liver steatosis. Its use in clinical practice is further explored by investigating the quantitative relationships between LFC measured by quantitative ultrasonography and metabolic diseases in a middle-aged and elderly Chinese population. METHODS: Liver fat content was measured by the quantitative ultrasound method in 4,916 participants from the Shanghai Changfeng Community Study. The anthropometric and serum biochemical parameters related to glucose and lipid metabolism were detected for each participant. The carotid artery intima-media thickness (CIMT) was measured by ultrasonography. RESULTS: The LFC displayed a non-Gaussian and positively skewed distribution in the community population and was significantly correlated with body weight, serum glucose, lipid profile, and CIMT. The 95th percentile of LFC in the subgroup of participants without any metabolic disease was 10.8%, and a LFC ≥ 10% was correlated with remarkable increases in the risks for glucose and lipid metabolic diseases. CONCLUSIONS: The quantitative ultrasound method that was developed for measuring LFC was useful in a population study. A LFC ≥ 10% might help to identify the subjects with an increased risk for metabolic diseases.

Tetramethylpyrazine protects palmitate-induced oxidative damage and mitochondrial dysfunction in C2C12 myotubes.

AIMS: Tetramethylpyrazine (TMP), one of the active ingredients isolated from a Chinese herbal prescription, possesses protective effects against oxidative stress caused by high glucose in endothelial cells. In this study, the role of TMP in preventing muscle cells from palmitate-induced oxidative damage was investigated and the possible mechanisms of action elucidated. MAIN METHODS: Mitochondrial reactive oxygen species (ROS) were measured in C2C12 myotubes, a palmitate-induced oxidative stress cell model, with or without TMP. Both mitochondrial membrane potential (MMP) and oxygen consumption were assessed in conjunction with quantification of mitochondrial DNA and mitochondrial biogenesis-related factors, such as peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (Tfam), by real-time polymerase chain reaction. Expression of mitochondrial respiratory chain complex III as an index of mitochondrial function was evaluated by immunoblotting, and glucose transport into the C2C12 myotube examined by analyzing 2-deoxy-[(3)H]glucose uptake. KEY FINDINGS: TMP significantly alleviated palmitate-induced mitochondrial ROS production, mitigated mitochondrial dysfunction and increased D-loop mRNA expression as compared with the control. This was accompanied by a marked reversal of palmitate-induced down-regulation in the expression of mitochondrial biogenesis-related factors (PGC1α, NRF1 and Tfam) and decreased glucose uptake in C2C12 myotubes. As a result, cell respiration, as reflected by the elevated expression of mitochondrial respiratory chain complex III and oxygen consumption, was enhanced. SIGNIFICANCE: TMP is capable of protecting C2C12 myotubes against palmitate-induced oxidative damage and mitochondrial dysfunction, and improving glucose uptake in muscle cells partially through the up-regulation of mitochondrial biogenesis.