Xiaoping Pan

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

BACKGROUND & AIMS Fibroblast 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. METHODS Serum 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. RESULTS Serum 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. CONCLUSIONS These 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.

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.

Serum Fibroblast Growth Factor 21 Is Associated with Adverse Lipid Profiles and γ-Glutamyltransferase But Not Insulin Sensitivity in Chinese Subjects

OBJECTIVE Fibroblast growth factor (FGF) 21, a hormone primarily secreted by liver, has recently been shown to have beneficial effects on glucose and lipid metabolism and insulin sensitivity in animal models. This study investigated the association of serum FGF21 levels with insulin secretion and sensitivity, as well as circulating parameters of lipid metabolism and hepatic enzymes in Chinese subjects. DESIGN Serum FGF21 levels were determined by ELISA in 134 normal glucose tolerance (NGT), 101 isolated-impaired fasting glucose, and 118 isolated-impaired glucose tolerance (I-IGT) Chinese subjects, and their association with parameters of adiposity, glucose, and lipid profiles, and levels of liver injury markers was studied. In a subgroup of this study, the hyperglycemic clamp technique was performed in 31 NGT, 17 isolated-impaired fasting glucose, and 15 I-IGT subjects to measure insulin secretion and sensitivity to test the associations with serum FGF21. RESULTS The serum FGF21 levels in I-IGT were significantly higher than NGT subjects [164.6 pg/ml (89.7, 261.0) vs. 111.8 pg/ml (58.0, 198.9); P < 0.05], and correlated positively with several parameters of adiposity. Multiple stepwise regression analysis showed an independent association of serum FGF21 with serum triglycerides, total cholesterol, and gamma-glutamyltransferase (all P < 0.05). However, FGF21 did not correlate with insulin secretion and sensitivity, as measured by hyperglycemic clamp and a 75-g oral glucose tolerance test. CONCLUSIONS Serum levels of FGF21 are closely related to adiposity, lipid metabolism, and biomarkers of liver injury but not insulin secretion and sensitivity in humans.

Relationship between serum osteocalcin and glycaemic variability in Type 2 diabetes

1. Recent reports have described the role of osteocalcin in glucose metabolism and glycaemic variability has been proven to be associated with an increased risk of diabetes complications. However, the relationship between osteocalcin and glycaemic variability remains unclear. The aim of the present study was to examine the relationship between serum osteocalcin and glycaemic variability, as determined by a continuous glucose monitoring (CGM) system in patients with Type 2 diabetes mellitus (T2DM).

Serum osteocalcin levels in relation to metabolic syndrome in Chinese postmenopausal women.

ObjectiveIt has been revealed that osteocalcin is a regulator of energy metabolism. We investigated the relationship between serum osteocalcin levels and metabolic syndrome (MetS) in Chinese postmenopausal women. MethodsA total of 1,789 postmenopausal women, aged 41 to 78 years, were selected from four communities in Shanghai, China. Serum levels of osteocalcin were measured with an electrochemiluminescence immunoassay. The diagnostic definition of MetS followed the 2007 Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults. ResultsSerum osteocalcin levels were significantly lower in participants with MetS than in non-MetS participants (median [interquartile range], 18.51 [15.52-23.46] vs 21.09 [16.98-26.26] ng/mL, P < 0.01). The frequency of MetS and its components decreased with increasing increments of serum osteocalcin levels (all P for trend < 0.05), with the exception of the frequency of low levels of high-density lipoprotein cholesterol. Serum osteocalcin levels significantly decreased with increasing number of metabolic disorders (P for trend < 0.01). Furthermore, binary logistic regression analysis revealed that participants with higher serum osteocalcin levels had lower odds ratios (ORs) for MetS (OR, 0.123; 95% CI, 0.053-0.283), central obesity (OR, 0.134; 95% CI, 0.060-0.299), and hyperglycemia (OR, 0.142; 95% CI, 0.066-0.302). ConclusionsSerum osteocalcin levels are negatively associated with MetS, particularly central obesity and hyperglycemia, in Chinese postmenopausal women.

Serum Levels of Fibroblast Growth Factor 19 Are Inversely Associated with Coronary Artery Disease in Chinese Individuals

Background The fibroblast growth factor 19 (FGF19) has been implicated in recent studies as a potential regulator of glucose and lipid metabolism, which may lead to atherosclerosis. Here, we investigated the association of FGF19 with the presence and severity of coronary artery disease (CAD) in a Chinese population. Methods A total of 315 patients with suspected or established CAD, including 205 males and 110 postmenopausal females, were enrolled and assessed by coronary angiography. CAD severity was determined by the Gensini score. Serum FGF19 was measured by quantitative sandwich ELISA. Results FGF19 levels were not significantly different between male and female patients (median [interquartile range], 143.40 [87.96–250.80] vs. 141.60 [87.13–226.32] pg/mL, P = 0.773). CAD patients had lower levels of FGF19 than those without CAD (128.20 [80.62–226.58] vs. 188.00 [105.10–284.70] pg/mL, P = 0.007). FGF19 was negatively correlated with 2hPG (r = –0.150, P = 0.008), FINS (r = –0.169, P = 0.004), HOMA-IR (r = –0.171, P = 0.004), and the Gensini score (r = –0.141, P = 0.012), but positively correlated with HDL-c (r = 0.116, P = 0.041) and adiponectin (r = 0.128, P = 0.024). Moreover, FGF19 was found to be independently correlated with 2hPG (β = –0.146, P = 0.022) and adiponectin (β = 0.154, P = 0.016). After adjusting for other CAD risk factors, FGF19 was demonstrated to be an independent factor for Gensini score (β = –0.140, P = 0.019) and the presence of CAD (β = –1.248, P = 0.036). Conclusions Serum FGF19 is associated with the presence and severity of CAD in a Chinese population.

Glipizide controlled‐release tablets, with or without acarbose, improve glycaemic variability in newly diagnosed Type 2 diabetes

1. The aim of the present study was to compare the effects of glipizide controlled‐release (CR) tablets monotherapy with that of glipizide CR tablets plus acarbose on glycaemic variability in newly diagnosed Type 2 diabetes (T2DM) patients using a continuous glucose‐monitoring system (CGMS).

Serum Adipocyte Fatty Acid Binding Protein Levels Are Positively Associated With Subclinical Atherosclerosis in Chinese Pre- and Postmenopausal Women With Normal Glucose Tolerance

CONTEXT Recent studies highlight a critical interaction between adipocyte fatty acid binding protein (A-FABP) and cardiovascular disorders. However, associations of A-FABP with subclinical atherosclerosis in a population with normal glucose tolerance remain unknown. OBJECTIVE The study aimed to evaluate the relationship between A-FABP and carotid intima-media thickness (C-IMT) in a Chinese population with normal glucose tolerance. DESIGN AND SETTING A cross-sectional analysis was conducted of 2253 cardiovascular disease-free normal glucose tolerance subjects (835 men, 1418 women; 20-78 years old) from the Shanghai Obesity Study. MAIN OUTCOME AND MEASURES C-IMT was measured by B-mode ultrasound and used to assess subclinical atherosclerosis. Serum A-FABP levels were quantified by a sandwich ELISA. RESULTS The median serum level for A-FABP was 4.0 ng/mL (interquartile range: 2.6-6.0 ng/mL), and significantly higher in women than men (P < .001). After adjusting for age and body mass index (BMI), a partial correlation analysis showed that A-FABP levels correlated with C-IMT in men, premenopausal, and postmenopausal women (P = .024, .006, and .016, respectively). Furthermore, C-IMT increased along with quartile A-FABP values (all P for trend <.001). Regression analyses demonstrated that A-FABP was associated with C-IMT only in women (P = .044 and .001 for pre- and postmenopausal, respectively). Moreover, A-FABP was identified as a risk factor for C-IMT in pre- and postmenopausal women with a normal BMI (P < .001 and P = .012, respectively). CONCLUSIONS Serum A-FABP levels independently and positively correlate with subclinical atherosclerosis in pre- and postmenopausal Chinese women with normal glucose tolerance after adjustments for the traditional risk factors.

Serum pigment epithelium-derived factor levels are independently correlated with the presence of coronary artery disease.

BackgroundPigment epithelium-derived factor (PEDF) has been proved to be closely correlated with metabolic syndrome (MetS) and its components that are all risk factors of cardiovascular disease and may play a protective role against vascular injury and atherosclerosis. The present study was designed to investigate the relationship between serum PEDF and coronary artery disease (CAD).MethodsA total of 312 consecutive in-patients (including 228 with CAD and 197 with MetS) who underwent coronary angiography were enrolled. Serum PEDF was measured by sandwich enzyme immunoassay and used to carry out multivariate stepwise regression analysis to assess correlation with patient demographic and clinical parameters. Multiple logistic regression analysis was performed to identify factors independently correlated with CAD.ResultsPatients with MetS had significantly higher levels of serum PEDF than non-MetS subjects (11.1(8.2, 14.2) vs. 10.1(7.6, 12.4) μg/mL; P < 0.05). Patients with CAD also had significantly higher serum PEDF than non-CAD subjects (11.0(8.1, 14.2) vs. 10.3(8.1, 12.8) μg/mL; P < 0.05). Triglyceride (TG), C-reactive protein (CRP), estimated glomerular filtration rate (eGFR), and hypoglycemic therapy were independently correlated with serum PEDF levels, and serum PEDF was independently positively correlated with CAD.ConclusionsSerum PEDF levels are independently positively associated with CAD in a Chinese population. Elevated PEDF may act as a protective response against vascular damage and subsequent CAD.

Serum lipocalin-2 levels positively correlate with coronary artery disease and metabolic syndrome

BackgroundThe lipocalin-2 (LCN2) cytokine, primarily known as a protein of the granules of human neutrophils, has been recently reported to be implicated in metabolic and inflammatory disorders. This study was designed to evaluate the relationship between serum LCN2 levels and coronary artery disease (CAD).MethodsSerum LCN2 levels of 261 in-patients who underwent coronary angiography were measured by sandwich enzyme immunoassay. Demographic (169 men and 92 postmenopausal women) and clinical (metabolic syndrome (MS), triglyceride (TG) and C-reactive protein (CRP) levels) characteristics were collected to assess independent factors of CAD (CAD: 188 and non-CAD: 73) and serum LCN2 levels by multiple logistic regression and multivariate stepwise regression analyses, respectively.ResultsSerum LCN2 levels were significantly higher in men (37.5 (27.4-55.4) vs. women: 28.2 (18.7-45.9) ng/mL, p < 0.01) and men with CAD (39.2 (29.3-56.5) vs. non-CAD men: 32.7 (20.5-49.7) ng/mL, p < 0.05), and showed significant positive correlation with CAD in men (odds ratio = 2.218, 95% confidence interval: 1.017-4.839). Similarly, serum LCN2 levels were significantly higher in men with MS (40.2 (31.9-59.4) vs. non-MS: 32.0 (21.7-47.6) ng/mL, p < 0.01) and showed a significant positive correlation with the number of MS components (p for trend < 0.05). No significant differences or correlations were seen in women. TG and neutrophils (standard β = 0.238 and 0.173) were independent factors of serum LCN2 levels in men, and only neutrophils (standard β = 0.286) affected levels in women (all p < 0.05).ConclusionsIncreased serum LCN2 levels are positively correlated with the presence of CAD and MS in a Chinese cohort.