Publications by authors named "Chunjun Sheng"

23 Publications

  • Page 1 of 1

Glucagon-like Peptide-1 Improves Fatty Liver and Enhances Thermogenesis in Brown Adipose Tissue via Inhibiting BMP4-Related Signaling Pathway in High-Fat-Diet-Induced Obese Mice.

Int J Endocrinol 2021 26;2021:6620289. Epub 2021 Apr 26.

Thyriod Research Center of Shanghai, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Tongji University, Shanghai 200072, China.

Objective: Glucagon-like peptide-1 (GLP-1) receptor agonist is effective in decreasing blood glucose and body weight. It could improve fatty liver with unclear mechanisms. Hence, we aimed to explore whether GLP-1 could improve fatty liver by regulating the BMP4-related signaling pathway.

Methods: Fifteen C57BL/6 mice were randomly assigned to 3 groups. Group A and Group B were fed with a high-fat diet (HFD) to induce fatty liver while Group C was fed with a regular diet (RD) for 24 weeks. Group A and Group B received a subcutaneous injection of exenatide and vehicle (0.9% NaCl), respectively, once daily at doses of 10 nmol/kg during the last 8 weeks. Bodyweight, liver weight, and lipid levels were measured. Histological analyses of liver tissue were performed. The expression of protein and gene measured by western blotting and real-time polymerase chain reaction (RT-PCR) was compared.

Results: Eight-week exenatide treatment significantly decreased body weight in Group A (from 44.08 ± 2.89 g to 39.22 ± 1.88 g,  = 0.045). Group A had lower body weight and liver weight than Group B at 24 weeks (39.22 ± 1.88 g vs. 47.34 ± 2.43 g,  = 0.001 and 1.70 ± 0.20 g vs. 2.48 ± 0.19 g,  = 0.001, respectively). Moreover, Group A showed significantly less liver steatosis than Group B. Additionally, Group A led to slightly decreased serum triglyceride (TG) and cholesterol (TC) levels compared to Group B. Western blotting showed that exenatide could prevent HFD-induced upregulation of BMP4 levels and downstream activation of Smad1/5/8 and the P38 MAPK signaling pathway in the liver. Furthermore, exenatide treatment could reduce BMP4 and enhance UCP-1 (an important thermogenin) in brown adipose tissue (BAT).

Conclusion: Exenatide could improve HFD-induced hepatic steatosis and enhance thermogenesis in BAT, which may be partly attributed to the inhibition of the BMP4-related signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6620289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093078PMC
April 2021

Low 25-hydroxyvitamin D is associated with arterial stiffness in Chinese with Type 2 diabetes mellitus.

Eur J Clin Nutr 2021 Mar 31. Epub 2021 Mar 31.

Department of Endocrinology and Metabolism, Tongji University School of Medicine, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.

Objectives: Arterial stiffness (AS), one of the complications of diabetes, associated with many metabolic factors. This study aimed to investigate the association between 25-hydroxyvitamin D(25(OH)D) and AS in type 2 diabetes mellitus (T2DM).

Methods: We identified 1335 diabetic patients from the Department of Endocrinology, Shanghai Tenth People's Hospital. Finally, 603 T2DM patients were included in the study. They were divided into two groups: AS group (baPWV ≥ 15,500 cm/s) and the control group (baPWV < 1550 cm/s).

Results: (1) Heart rate (HR) and systolic pressure (SBP) were higher while body weight and body mass index (BMI) were smaller in AS group than the control group (all P < 0.05). (2) Compared to patients without AS, patients with AS showed lower 25(OH)D and higher rate of 25(OH)D deficiency (42 ± 16 vs. 45 ± 17 mol/l, 68% vs. 64%, all P < 0.05). (3) BaPWV was negatively associated with 25(OH)D (r = -0.12, P = 0.004), while positively associated with age, duration of diabetes, HR, SBP, and low-density lipoprotein cholesterol and negatively associated with body weight and BMI (all P < 0.05). (4) Multiple linear regression showed that 25(OH)D was the negatively influencing factor of baPWV (β = -2.2, P = 0.01). Logistic regression showed that age and SBP were risk factor of AS (OR:1.07, 95% CI: 1.05-1.10, P < 0.001; OR:1.03, 95% CI: 1.02-1.04, P < 0.001) while 25(OH)D was protective factor of AS (OR:0.987, 95% CI: 0.976-0.998, P = 0.024).

Conclusions: T2DM patients with AS had lower 25(OH)D and higher rate of 25(OH)D deficiency. There was a negative relationship between 25(OH)D and AS assessed by baPWV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41430-021-00870-0DOI Listing
March 2021

Glucose-Lipid Metabolism in Obesity with Elevated Prolactin Levels and Alteration of Prolactin Levels After Laparoscopic Sleeve Gastrectomy.

Obes Surg 2020 10 22;30(10):4004-4013. Epub 2020 Jul 22.

Department of Endocrinology and Metabolism, School of Medicine, Shanghai Tenth People's Hospital of Tongji University, No. 301 Middle Yanchang Road, Shanghai, 200072, China.

Purpose: We investigated the differences in metabolism between obesity with or without increased prolactin (PRL) and the change in PRL after laparoscopic sleeve gastrectomy (LSG).

Methods: Patients were divided into two groups: obesity with normal PRL (NP, n = 123) and high PRL (HP, n = 108). Glucose-lipid metabolism and inflammation were measured. A total of 115 patients with obesity (NP, n = 64; HP, n = 51) underwent LSG were recruited, and PRL was measured at 12 months after LSG.

Results: (1) Blood glucose (BG), total cholesterol (TCH), LDL, triglyceride, and TNF-α were lower in the HP than in the NP group in the cross-sectional study (all P < 0.05). (2) PRL was negatively associated with neck circumference, waist-to-hip ratio, systolic blood pressure, heart rate, basal metabolism rate (BMR), ALP, TCH, and LDL in all subjects. PRL levels were positively associated with weight, HC, and BMR in males but were negatively associated with ALT, AST, ALP, BG 30 min, BG 60 min, FFA, and TCH in females (all P < 0.05). (3) Regression analysis showed that PRL negatively correlated with ALP and LDL-C in the whole baseline (β = - 0.051, P = 0.002; β = - 1.372, P = 0.033). PRL was a negative factor for ALP in females and a positive factor for BMR2 in males (β = - 0.099, P = 0.041; β = 0.005, P = 0.006). (4) PRL decreased in the HP group and increased in the NP group at 12 months post-operation (all P < 0.05). Increased PRL was associated with a change in TCH in the NP group (P < 0.05).

Conclusion: Increased PRL resulted in improved glucose-lipid metabolism and chronic low-grade inflammation. LSG led to increased PRL in NP and decreased PRL in HP. Improved lipid was associated with increased PRL in NP after surgery.

Clinical Trial Registration Number: ChiCTR-OCS-12002381.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11695-020-04771-2DOI Listing
October 2020

Gender difference in the relationship between serum uric acid reduction and improvement in body fat distribution after laparoscopic sleeve gastrectomy in Chinese obese patients: a 6-month follow-up.

Lipids Health Dis 2018 Dec 20;17(1):288. Epub 2018 Dec 20.

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No.301 Middle Yanchang Road, Shanghai, 200072, China.

Background: Hyperuricemia is related to obesity and fat accumulation. This study aimed to observe the effects of laparoscopic sleeve gastrectomy (LSG) on serum uric acid (sUA) level and body fat distribution in obese patients. The relationships between post-LSG improvement in sUA levels and body fat distribution changes, as well as their sex-related differences, were also explored.

Methods: In total, 128 obese patients (48 men; 80 women) who underwent LSG were enrolled. Anthropometric indicators, glucose and lipid metabolic indicators, and sUA levels were measured pre-LSG and 6 months post-LSG. The body compositions were measured via dual-energy X-ray absorptiometry. The patients were divided into normal-sUA (NUA) and high-sUA (HUA) groups based on preoperative sUA levels.

Results: Compared with the NUA group, the reduction of sUA levels 6 months post-LSG was more significant in the HUA group. In addition, sUA reduction in the female HUA group was more significant than that of the male HUA group (P < 0.01). Changes in serum uric acid levels (ΔsUA) in the male HUA group was positively correlated with changes in body weight, body mass index, neck circumference, and hip circumference (r = 0.618, 0.653, 0.716, and 0.501, respectively; P < 0.05 in all cases). It was also positively correlated with changes in fat mass in the gynoid region, android region, and legs, (r = 0.675, 0.551, and 0.712, respectively; P < 0.05 in all cases), and negatively correlated with changes in total testosterone (ΔTT) (r = - 0.517; P = 0.040). Furthermore, ΔTT in this group was closely associated with the improved sex-related fat distribution. The ΔsUA in the female HUA group was positively correlated with changes in fasting serum C peptide and ΔLNIR (r = 0.449 and 0.449, respectively; P < 0.05 in both cases). In addition, it was also positively correlated with changes in visceral adipose tissue (VAT) fat mass, VAT fat volume, and VAT fat area (r = 0.749, 0.749, and 0.747, respectively; P < 0.01 in all cases).

Conclusions: sUA levels of obese patients with hyperuricemia improved 6 months after LSG. Reduction of sUA after LSG was correlated with improved body fat distribution, and the relationships also displayed sex-based differences. Uric acid might be an important metabolic regulator associated with fat distribution and sex hormones.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12944-018-0934-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302487PMC
December 2018

Positive association between serum uric acid and bone mineral density in Chinese type 2 diabetes mellitus stratified by gender and BMI.

J Bone Miner Metab 2018 Sep 9;36(5):609-619. Epub 2017 Nov 9.

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Accumulating evidence has demonstrated that serum uric acid (UA), a natural powerful antioxidant, plays a beneficial role in bone health in the general population. However, few reports are available on the association between serum UA and bone in patients with type 2 diabetes mellitus (T2DM). We therefore investigated whether the benefit of serum UA for bone health was still present in those patients. 626 males and 609 postmenopausal females with T2DM were enrolled in this cross-sectional study. Serum UA concentrations and bone mineral density (BMD) measured at lumbar spine, femoral neck and total hip by dual-energy X-ray absorptiometry were obtained from all subjects. Meanwhile, data on osteoporosis prevalence, glucose metabolism, bone turnover markers and other serum biochemical indexes were collected. After adjustment for potential confounders, the results suggested that serum UA was positively associated with BMD in patients with normal weight, but this positive association varied by gender and skeletal sites in overweight T2DM patients [body mass index (BMI) ≥ 25 kg/m]. Moreover, significantly lower odds ratios (ORs) for osteoporosis were found in postmenopausal patients with the highest UA tertile and male patients with medium UA tertile [adjusted OR 0.315, 95% confidence interval (CI) 0.170-0.581 for postmenopausal patients; adjusted OR 0.464, 95% CI 0.225-0.955 for male patients]. The positive association between serum UA and BMD found in Chinese T2DM patients may imply that relatively high UA is a protective factor for bone in these patients. Large intervention studies are needed to further confirm the outcomes and provide possible explanations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00774-017-0877-9DOI Listing
September 2018

The clinical characteristics of patients with mitochondrial tRNA Leu(UUR)m.3243A > G mutation: Compared with type 1 diabetes and early onset type 2 diabetes.

J Diabetes Complications 2017 Aug 29;31(8):1354-1359. Epub 2017 Apr 29.

Department of Endocrinology & Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, China.

Objective: This study presents nine patients with mitochondrial tRNA Leu (UUR) m.3243A>G mutation and compares the clinical characteristics and diabetes complications with type 1 diabetes (T1DM) or early onset type 2 diabetes (T2DM).

Methods: The study covers 9 patients with MIDD, 33 patients with T1DM and 86 patients (age of onset ≤35years) with early onset T2DM, matched for sex, age at onset of diabetes, duration of diabetes. All patients with MIDD were confirmed as carrying the m.3243A>G mitochondrial DNA mutation. Serum HbA1c, beta-cell function, retinal and renal complications of diabetes, bone metabolic markers, lumbar spine and femoral neck BMD bone mineral density were compared to characterize the clinical features of all patients.

Results: Nine patients were from five unrelated families, and the mean (SD) onset age of those patients was 31.2±7.2year. Two patients required insulin at presentation, and six patients progressed to insulin requirement after a mean of 7.2years. β-Cell function in the MIDD group was intermediate between T1DM and early-onset T2DM. In MIDD, four patients were diagnosed as diabetic retinopathy (4/9) and five patients (5/9) had macroalbuminuria. The number of patients with diabetic retinopathy and macroalbuminuria in the MIDD group was comparable to T1DM or early-onset T2DM. The rate of osteoporosis (BMD T-score<-2.5 SD) in the patient with MIDD was higher than the T1DM or early-onset T2DM group.

Conclusion: Our study indicates that of the nine subjects with MIDD, three patients (1-II-1, 1-II-3, 1-II-4) who came from the same family had a history of acute pancreatitis. Compared with T1DM or early-onset T2DM matched for sex, age, duration of diabetes, MIDD patients had the highest rate of osteoporosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jdiacomp.2017.04.001DOI Listing
August 2017

Performance of a new real-time continuous glucose monitoring system: A multicenter pilot study.

J Diabetes Investig 2018 Mar 7;9(2):286-293. Epub 2017 Jul 7.

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Aims/introduction: The present study aimed to investigate the performance of a new real-time continuous glucose monitoring system.

Materials And Methods: Interstitial glucose levels were monitored for 7 days in 63 patients with type 1 or type 2 diabetes using the Medtrum A6 TouchCare CGM System. Venous blood was collected on a randomized day of the wear period. Plasma glucose levels were measured as reference values.

Results: Among 1,678 paired sensor-reference values, 90.5% (95% confidence interval 89.1-91.9%) were within ±20%/20 mg/dL of the reference values, with a mean absolute relative difference of 9.1 ± 8.7% (95% CI: 8.9-9.2%). The percentages of paired sensor-reference values falling within zone A and B of the Clarke error grid analysis (EGA) and the type 1 diabetes consensus EGA were 99.1 and 99.8%. Continuous EGA showed that the percentages of accurate readings, benign errors, and erroneous readings were 89.9, 6.3 and 3.8%, respectively. Surveillance EGA showed that 90.6, 9.2, and 0.2% of sensor-reference values with no, slight and lower moderate risk, respectively. The mean absolute relative difference was 16.6, and 96.0% of the sensor values fell within zones A and B of the consensus EGA for hypoglycemia. More than 85% of sensor values were within ±20%/20 mg/dL of reference values, the mean absolute relative difference was <11, and >99.5% of the sensor values fell in zones A and B of the consensus EGA.

Conclusions: The Medtrum real-time continuous glucose monitoring system was numerically and clinically accurate over a large glucose range across 7 days of wear.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jdi.12699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835467PMC
March 2018

The Associations of Serum Uric Acid with Obesity-Related and Related Metabolic Indices.

Int J Endocrinol 2017 7;2017:5438157. Epub 2017 Mar 7.

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

. Recent studies have shown that hyperuricemia (HUA) is associated with hypertension, dyslipidemia, insulin resistance, and metabolic syndrome (MetS). We aimed to examine the relationship of serum UA with (AN) and related metabolic indices in obese patients. A cross-sectional study with 411 obese patients recruited from our department was analyzed in this study. Weight, body mass index (BMI), UA, lipid profile, liver function, and renal function were measured in all participants. Oral glucose tolerance tests were performed, and serum glucose, insulin, and C peptide were measured at 0, 30, 60, 120, and 180 min. AN group had higher serum UA levels than OB group. Circulating UA levels were associated with BMI, dyslipidemia, hypertension, IR, and AN. In logistic regression analyses (multivariable-adjusted), a high serum UA level was associated with high odds ratios (ORs) (95% confidence interval [CI]) for AN in females (ORs = 3.00 and 95% CI [1.02-8.84]) and males (ORs = 6.07 and 95% CI [2.16-17.06]) in the highest quartile (Q4) of serum UA. Serum UA levels were positively associated with multiple metabolic abnormalities including obesity, hypertension, hyperglycemia, hyperlipidemia, and AN and may be an important risk factor in the development of AN; further evidences in vitro and in vivo are needed to investigate the direct or indirect relationship.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2017/5438157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359528PMC
March 2017

The prevalence of thyroid nodules in northwest China and its correlation with metabolic parameters and uric acid.

Oncotarget 2017 Jun;8(25):41555-41562

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

This study aimed to estimate the prevalence of thyroid nodules (TN) and investigate its correlation with metabolic parameters, especially uric acid (UA) in northwest Chinese population. We conducted a large cross-sectional survey with 67,781 residents (33,020 men, 34,761 women), aged from 18 to 86 years in Shanxi, China, from January 2012 to December 2014. A thyroid ultrasound examination was performed with number and size of nodules being recorded. Metabolic parameters including body mass index (BMI), blood pressure (BP), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), fasting glucose (FG), and uric acid (UA) were also examined. Our study revealed that approximately 30.7% of men and 39.9% of women in Northwest China had TN, about half of which were multi-nodularity and a quarter of their TN larger than 1 cm. The prevalence of TN increased with aging and increasing BMI, and metabolic disorders, which also related to the increased incident of multi-nodularity and larger TN. Serum UA appeared to be a protective factor for TN in men older than 30 years, but a risk factor in both men younger than 30 years and women older than 30 years. This phenomenon needs to be further investigated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.14720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522227PMC
June 2017

Activated central galanin type 1 receptor alleviated insulin resistance in diabetic rat muscle.

J Neurosci Res 2016 10 13;94(10):947-55. Epub 2016 Jul 13.

Department of Endocrinology, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.

Evidence indicates that central galanin is involved in regulation of insulin resistance in animals. This study investigates whether type 1 galanin receptor (GAL1) in the brain mediates the ameliorative effect of galanin on insulin resistance in skeletal muscles of type 2 diabetic rats. Rats were intracerebroventricularly (i.c.v.) injected with galanin(1-13)-bradykinin(2-9) amide (M617), a GAL1 agonist, and/or Akti-1/2, an Akt inhibitor, via caudal veins once per day for 10 days. Insulin resistance in muscle tissues was evaluated by glucose tolerance and 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) tests, peroxisome proliferator-activated receptor-γ (PPARγ), glucose transporter 4 (GLUT4) mRNA expression levels, Akt phosphorylation, and GLUT4 and vesicle-associated membrane protein 2 (VAMP2) concentration at plasma membranes in muscle cells. The results show that i.c.v. treatment with M617 increased glucose tolerance, 2-NBDG uptake, PPARγ levels, Akt phosphorylation, GLUT4 protein, and GLUT4 mRNA expression levels as well as GLUT4 and VAMP2 concentration at plasma membranes. All increases may be blocked by pretreatment with Akti-1/2. These results suggest that activated central GAL1 may trigger the Akt signaling pathway to alleviate insulin resistance in muscle cells. Therefore, the impact of galanin on insulin resistance is mediated mainly by GAL1 in the brain, and the GAL1 agonist may be taken as a potential antidiabetic agent for treatment of type 2 diabetes mellitus. © 2016 Wiley Periodicals, Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jnr.23775DOI Listing
October 2016

Reversibility of β-Cell-Specific Transcript Factors Expression by Long-Term Caloric Restriction in db/db Mouse.

J Diabetes Res 2016 21;2016:6035046. Epub 2016 Feb 21.

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University, 301 Middle Yanchang Road, Shanghai 200072, China.

Type 2 diabetes (T2D) is characterized by β-cell dedifferentiation, but underlying mechanisms remain unclear. The purpose of the current study was to explore the mechanisms of β-cell dedifferentiation with and without long-term control of calorie intake. We used a diabetes mouse model (db/db) to analyze the changes in the expression levels of β-cell-specific transcription factors (TFs) and functional factors with long-term caloric restriction (CR). Our results showed that chronic euglycemia was maintained in the db/db mice with long-term CR intervention, and β-cell dedifferentiation was significantly reduced. The expression of Glut2, Pdx1, and Nkx6.1 was reversed, while MafA expression was significantly increased with long-term CR. GLP-1 pathway was reactivated with long-term CR. Our work showed that the course of β-cell dedifferentiation can intervene by long-term control of calorie intake. Key β-cell-specific TFs and functional factors play important roles in maintaining β-cell differentiation. Targeting these factors could optimize T2D therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2016/6035046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779534PMC
December 2016

Preventative Sleeve Gastrectomy Contributes to Maintaining β Cell Function in db/db Diabetic Mouse.

Obes Surg 2016 10;26(10):2402-10

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tong-Ji University, 301 Middle Yan-Chang Road, ShangHai, 200072, China.

Background: We used the leptin-receptor (LPR)-deficient mice model (db/db), a spontaneous model of type 2 diabetes with early β cell dysfunction to determine whether a preventative sleeve gastrectomy (SG) is an effective technique for the treatment of β cell failure.

Methods: The animals operated at an early stage of life, prior to metabolic alterations, were used to study the molecular mechanisms of β cell function improvement after a SG.

Results: β cell function was significantly increased, and islet morphology remained normal, after the SG. The expression of Glut2, Pdx1, MafA, and Nkx6.1 were significantly increased after the SG. The expression of GLP-1 in the colonic tissue, as well as GLP-1R and PKC in islets, was significantly increased after the SG.

Conclusions: β cell dysfunction can be ameliorated by a preventative SG for db/db mice. Maintaining the GLP-1 pathway and key transcript factor (TF) activation contributes to the improvement of β cell function after a preventative SG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11695-016-2112-5DOI Listing
October 2016

Upregulated Pdx1 and MafA Contribute to β-Cell Function Improvement by Sleeve Gastrectomy.

Obes Surg 2016 Apr;26(4):904-9

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tong-Ji University, 301 Middle Yan-Chang Road, Shanghai, 200072, China.

Purpose: Sleeve gastrectomy is an effective technique for the treatment of severe obesity, and its effects on the improved β-cell function have not yet been fully understood.

Materials And Methods: From February 2014 to July 2015, sleeve gastrectomy was performed in 5 patients with T2D, who were assessed before and after sleeve gastrectomy (SG). Moreover, a high-fat-diet (HFD) mouse model was also used to study the molecular mechanisms of β-cell functional improvement after SG.

Results: The glucose-stimulated acute insulin response was restored in the T2D patients after SG. The expression of GLP-1 in colonic tissue as well as β-cell specific transcription factors (TFs), Pdx1, and MafA in islets was significantly increased after SG.

Conclusion: β-cell dysfunction can be ameliorated by SG. The re-activation of key TFs contributes to the improvement of β cell function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11695-016-2068-5DOI Listing
April 2016

Eosinophils Reduce Chronic Inflammation in Adipose Tissue by Secreting Th2 Cytokines and Promoting M2 Macrophages Polarization.

Int J Endocrinol 2015 25;2015:565760. Epub 2015 Nov 25.

Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.

Obesity is now recognized as a low-grade, chronic inflammatory disease that is linked to a myriad of disorders including cardiovascular diseases, type 2 diabetes, and liver diseases. Recently it is found that eosinophils accelerate alternative activation macrophage (AAM) polarization by secreting Th2 type cytokines such as interleukin-4 and interleukin-13, thereby reducing metainflammation in adipose tissue. In this review, we focused on the role of eosinophils in regulating metabolic homeostasis and obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/565760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673347PMC
December 2015

THE CLINICAL AND METABOLIC CHARACTERISTICS OF YOUNG-ONSET KETOSIS-PRONE TYPE 2 DIABETES IN CHINA.

Endocr Pract 2015 Dec 15;21(12):1364-71. Epub 2015 Sep 15.

Objective: To investigate the prevalence and clinical characteristics of ketosis-prone type 2 diabetes (KPD) in Chinese patients with young-onset diabetes.

Methods: A total of 238 young diabetic patients were recruited from our inpatient department from January 1, 2012, to December 28, 2014. KPD was defined as diabetes without precipitating illness and with the presence of ketosis or diabetic ketoacidosis in the absence of autoantibodies at the time of diagnosis. We reviewed the clinical characteristics and disease progression of this group of patients.

Results: Eighteen patients fulfilled the criteria for KPD, and the prevalence of patients with KPD was 7.6%. The mean (SD) age of the KPD group at the time of diagnosis of diabetes was 27.6 (4.85) years, and these patients were predominantly male (male to female ratio, 8:1) and had a high proportion of obesity and new-onset diabetes and a strong family history of diabetes. β-Cell function in the KPD group was intermediate between type 1 and type 2 diabetes. Patients with KPD had the highest levels of glycated hemoglobin, triglycerides, total cholesterol, and free fatty acids and the lowest levels of high-density lipoprotein. After 3 to 12 months of follow-up, 17 of 18 patients with KPD (94.4%) were able to discontinue insulin therapy, and 11 patients (61.1%) were managed with diet or exercise alone.

Conclusion: KPD patients accounted for 7.6% of the diabetic patients requiring admission to a large urban hospital in China, with an age of onset of diabetes of ≤35 years. These patients are more likely to be male, have abnormal lipid metabolism, and have more reversible β-cell dysfunction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4158/EP15778.ORDOI Listing
December 2015

BRAFV600E mutation in papillary thyroid microcarcinoma: a meta-analysis.

Endocr Relat Cancer 2015 Apr 15;22(2):159-68. Epub 2015 Jan 15.

Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Neurology and NeuroscienceWeill Cornell Medical College, New York, New York 10065, USADepartments of Nuclear MedicineUltrasound MedicineShanghai Tenth People's Hospital, Shanghai 200072, ChinaThyroid InstituteTongji University, Shanghai 200072, ChinaDivision of EndocrinologyDiabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Middle Road, Shanghai 200072, ChinaFirst Clinical Medical CollegeNanjing Medical University, Nanjing 210029, ChinaJiangsu Institute of Nuclear MedicineWuxi 214063, ChinaDepartment of CardiologyShanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment o

The prognostic value of the BRAFV600E mutation, resulting in poor clinical outcomes of papillary thyroid carcinoma, has been generally confirmed. However, the association of BRAFV600E with aggressive clinical behaviors of papillary thyroid microcarcinoma (PTMC) has not been firmly established in individual studies. We performed this meta-analysis to examine the relationship between BRAFV600E mutation and the clinicopathological features of PTMC. We conducted a systematic search in PubMed, EMBASE, and the Cochrane library for relevant studies. We selected all the studies that reported clinicopathological features of PTMC patients with information available on BRAFV600E mutation status. Nineteen studies involving a total of 3437 patients met these selection criteria and were included in the analyses. The average prevalence of the BRAFV600E mutation was 47.48%, with no significant difference with respect to patient sex (male versus female) and age (younger than 45 years versus 45 years or older). Compared with the WT BRAF gene, the BRAFV600E mutation was associated with tumor multifocality (odds ratio (OR) 1.38; 95% CI, 1.04-1.82), extrathyroidal extension (OR 3.09; 95% CI, 2.24-4.26), lymph node metastases (OR 2.43; 95% CI, 1.28-4.60), and advanced stage (OR 2.39; 95% CI, 1.38-4.15) of PTMC. Thus, our findings from this large meta-analysis definitively demonstrate that BRAFV600E-mutation-positive PTMC are more likely to manifest with aggressive clinicopathological characteristics. In appropriate clinical settings, testing for the BRAFV600E mutation is likely to be useful in assisting the risk stratification and management of PTMC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/ERC-14-0531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629836PMC
April 2015

Molecular and phenotypic characteristics of maturity-onset diabetes of the young compared with early onset type 2 diabetes in China.

J Diabetes 2015 Nov 24;7(6):858-63. Epub 2015 Mar 24.

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Background: The aim of the present study was to investigate the contribution of maturity-onset diabetes of the young (MODY) genes to the etiology of 14 Chinese MODY families and to assess phenotypic differences between patients with MODY but without a known genetic cause of diabetes (MODYX) and those with early onset type 2 diabetes (T2D).

Methods: The study included 14 MODY probands from unrelated families and 59 patients (age of onset ≤35 years) diagnosed as early onset T2D. A standard meal test and metabolic studies were performed to characterize the clinical features of all patients. All probands with MODY were analyzed for nucleotide variations in promoters, exons, and exon-intron boundaries of 13 known MODY genes by direct DNA sequencing.

Results: Mutations in 13 known MODY genes were not present in the 14 Chinese families and they were classified as MODYX. However, different polymorphisms were identified, with I27L (42.9%; 12/28) and S487N (46.4%; 13/28) of hepatocyte nuclear factor 4α (HNF1α/MODY3) being two most frequent polymorphisms. Two new polymorphisms, namely T412I and D504H, were detected in carboxyl ester lipase (CEL/MODY8). Compared with patients with early onset T2D, patients with MODYX were diagnosed with diabetes at a younger age (28.3 ± 6.5 vs 24.3 ± 6.5 years; P < 0.05) and had a lower body mass index (BMI; 28.3 ± 6.1 vs 24.1 ± 4.3 kg/m(2) ; P < 0.01) and homeostatic model assessment of β-cell function (47.6 [22.2-89.4] vs 18.5 [6.5-33.7]; P < 0.05).

Conclusion: Herein we report on 14 Chinese families with MODYX and describe its phenotype. Compared with early onset T2D, MODYX is characterized by lower BMI and decreased insulin-secreting capacity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1753-0407.12253DOI Listing
November 2015

Association between alendronate and atypical femur fractures: a meta-analysis.

Endocr Connect 2015 Mar 23;4(1):58-64. Epub 2014 Dec 23.

Department of EndocrinologyShanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Middle Road, Shanghai 200072, ChinaDepartment of Internal MedicineShanghai Dachang Hospital, Shanghai 200442, ChinaDepartment of PaediatricsNingbo Women and Children's Hospital, Ningbo, Zhejiang Province 315012, China.

Alendronate (ALN) is a commonly used drug for the treatment of osteoporosis. Atypical femur fractures (AFFs) have been associated with long-term use of ALN and have recently become the subject of considerable attention as ALN use increases. This meta-analysis aimed to determine the relationship between ALN and AFF. The Embase, PubMed, and Cochrane library databases were searched for relevant studies published before November 6, 2014. Studies clearly reporting the relationship between ALN and AFF were selected for our analysis. From these results, the relationship between ALN and AFF was analyzed. Weighted mean differences were calculated using a random-effects model. Five studies were included in this meta-analysis. The results revealed that the use of ALN will not increase the risk of AFF in short term (P>0.05), but there will be a risk of AFF (P<0.05) with long-term (>5 years) use of ALN. These findings indicate that long-term use of ALN is a risk factor for AFF and that more attention should be paid to the clinical applications of ALN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EC-14-0120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5402924PMC
March 2015

Risk of bone fractures associated with glucagon-like peptide-1 receptor agonists' treatment: a meta-analysis of randomized controlled trials.

Endocrine 2015 Feb 30;48(1):107-15. Epub 2014 Jul 30.

Department of Endocrinology, Shanghai Tenth People's Hospital, School of Medicine, Tong-Ji University, 301 Middle Yanchang Road, Shanghai, 200072, China.

Traditional anti-diabetic drugs may have negative or positive effects on risk of bone fractures. Yet the relationship between the new class glucagon-like peptide-1 receptor agonists (GLP-1 RA) and risk of bone fractures has not been established. We performed a meta-analysis including randomized controlled trials (RCT) to study the risk of bone fractures associated with liraglutide or exenatide, compared to placebo or other active drugs. We searched MEDLINE, EMBASE, and clinical trial registration websites for published or unpublished RCTs comparing the effects of liraglutide or exenatide with comparators. Only studies with disclosed bone fracture data were included. Separate pooled analysis was performed for liraglutide or exenatide, respectively, by calculating Mantel-Haenszel odds ratio (MH-OR). 16 RCTs were identified including a total of 11,206 patients. Liraglutide treatment was associated with a significant reduced risk of incident bone fractures (MH-OR=0.38, 95% CI 0.17-0.87); however, exenatide treatment was associated with an elevated risk of incident bone fractures (MH-OR=2.09, 95% CI 1.03-4.21). Publication bias and heterogeneity between studies were not observed. Our study demonstrated a divergent risk of bone fractures associated with different GLP-1 RA treatments. The current findings need to be confirmed by future well-designed prospective or RCT studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-014-0361-4DOI Listing
February 2015

Total osteocalcin in serum predicts testosterone level in male type 2 diabetes mellitus.

Int J Clin Exp Med 2014 15;7(4):1145-9. Epub 2014 Apr 15.

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai 200072, China.

Objective: To investigate the relationship between total osteocalcin (total OC) and testosterone level in the serum of male patients with type 2 diabetes mellitus (T2DM).

Methods: 98 male T2DM were recruited in our cross-section study. Their anthropometric parameters were measured and body mass index (BMI) was calculated. Serum markers including glucose, insulin, HbA1c, testosterone, total OC and other bone metabolic markers were examined. Simple Pearson correlation and multiple regression analysis were performed.

Results: Poor level of glucose control was found in the patients (HbA1c 9.19±2.53 and FPG 8.20±2.98). In simple Pearson correlation, total OC was positively related with testosterone (r=0.236, P=0.019), and this relation still existed after considering all the parameters of the patients (Model 1, 2 and 3).

Conclusion: In male patients with T2DM, total OC was positively correlated with testosterone, so total OC might predict the testosterone level in the serum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057876PMC
June 2014

TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer.

J Clin Endocrinol Metab 2014 Jun 11;99(6):E1130-6. Epub 2014 Mar 11.

Laboratory for Cellular and Molecular Thyroid Research (X.L., R.L., X.S., G.Z., A.K.M., M.X.), Division of Endocrinology, Diabetes & Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Endocrinology & Metabolism (S.Q., C.S.), Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Department of Endocrinology & Metabolism and Institute of Endocrinology (H.G., Z.S., W.T.), The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province 110001, China; Department of Pathology (H.Y.), Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China; Department of Endocrinology & Metabolism (Y.W.), The Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong Province 266003, China; and Jilin Provincial Key Laboratory of Surgical Translational Medicine (H.S.), Department of Thyroid and Parathyroid Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province 130033, China.

Context: Promoter mutations chr5:1,295,228C>T and chr5:1,295,250C>T (termed C228T and C250T, respectively) in the gene for telomerase reverse transcriptase (TERT) have been reported in various cancers and need to be further investigated in thyroid cancer.

Objective: The aim of the study was to explore TERT promoter mutations in various thyroid tumors and examine their relationship with BRAF V600E mutation, iodine intake, and clinicopathological behaviors of thyroid cancer.

Design: TERT promoter and BRAF mutations were identified by sequencing genomic DNA of primary thyroid tumors from normal- and high-iodine regions in China, and clinicopathological correlation was analyzed.

Results: The C228T mutation was found in 9.6% (39 of 408) of papillary thyroid cancer (PTC), C250T was found in 1.7% (7 of 408) of PTC, and they were collectively found in 11.3% (46 of 408) of PTC. C228T was found in 31.8% (7 of 22) and C250T in 4.6% (1 of 22) of follicular thyroid cancer (FTC), and they were collectively found in 36.4% (8 of 22) of FTC. No TERT mutation was found in 44 benign thyroid tumors. The two mutations occurred in 3.8% (6 of 158) of BRAF mutation-negative PTC vs 16.0% (40 of 250) of BRAF mutation-positive PTC (P = 5.87 × 10(-4)), demonstrating their association. Unlike BRAF mutation, TERT promoter mutations were not associated with high iodine intake, but they were associated with older patient age, larger tumor size, extrathyroidal invasion, and advanced stages III/IV of PTC. Coexisting TERT and BRAF mutations were even more commonly and more significantly associated with clinicopathological aggressiveness.

Conclusions: In this large cohort, we found TERT promoter mutations to be common, particularly in FTC and BRAF mutation-positive PTC, and associated with aggressive clinicopathological characteristics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2013-4048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4037723PMC
June 2014

Systematic review on the treatment of pentoxifylline in patients with non-alcoholic fatty liver disease.

Lipids Health Dis 2011 Apr 8;10:49. Epub 2011 Apr 8.

Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Background: As an anti-TNF agent that targets inflammatory process directly, Pentoxifylline has been investigated for treatment of NASH in individual studies and pilot trials for years. We summarized the available information and generating hypotheses for future research.

Data Sources: Google, Cochrane, MEDLINE, and EMBASE and the Chinese Biomedical data bases for studies restricted to pentoxifylline treatment in humans with NAFLD in all languages until June 2010. Six studies (2 randomized, double-blind, placebo-controlled trials; 4 prospective cohort studies) extracted from 11604 references.

Results: Pentoxifylline-treated patients showed a significant decrease AST (n=37, P=0.01) and ALT (n=50, P=0.03), but no significant effect on IL-6 (n=36, P=0.33) and TNF-α (n=68, P=0.26) compared with Placebo or UDCA-controlled groups. Improvement in one or more histological variables was reported in two trails, only 1 study showed a reduction in of one or two points in fibrosis stage.

Limitations: The trails did not consistently report all of the outcomes of interest. Sample sizes (117 patients totally) were small and only 2 out of 6 studies had a randomized, controlled design.

Conclusion: Pentoxifylline reduce AST and ALT levels and may improve liver histological scores in patients with NALFD/NASH, but did not appear to affect cytokines. Large, prospective, and well-designed randomized, controlled studies are needed to address this issue. Novel therapeutic targets for activation of inflammatory signaling pathways by fat also merit investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1476-511X-10-49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088890PMC
April 2011

The effect of thiazolidinediones on bone mineral density in Chinese older patients with type 2 diabetes.

J Bone Miner Metab 2010 16;28(1):77-81. Epub 2009 Jul 16.

Department of Endocrinology, Shanghai Tenth Hospital affiliated to Tongji University, 301# Middle YanChang Road, 200072 Shanghai, China.

The effect of thiazolidinediones (TZDs) on bone mineral density (BMD) and bone metabolism in patients with type 2 diabetes is still in debate. Accumulating evidence has emerged that long-term administration of TZDs may increase the occurrence of osteoporosis, at least in postmenopausal women. Because little clinical data has been reported on Chinese people, a retrospective study was performed. One-hundred ninety-eight Chinese people, all from our inpatients, were selected for a 24-28 month review (26 +/- 0.5 m). Four groups divided according to gender and TZD use were designated fTZD, mTZD, f and m. Changes of subjects' BMD and bone metabolism markers were noted and analyzed. Compared with group f, bone loss from fTZD in this over 24-month review was more significant in lumbar spine (L1-L4) (0.1 +/- 0.15 vs. 0.06 +/- 0.11) and right hip (0.09 +/- 0.15 vs. 0.05 +/- 0.14) (g/cm(3)) (P < 0.05). However, the opposite result was found in male patients with less bone loss in group mTZD. Two bone metabolism markers, including beta C-terminal telopeptide of type I collagen (beta-CTX) and osteocalcin (OC), in this study did not prove valuable in revealing changes among groups. We concluded that long-term TZD use may increase the risk of bone loss in Chinese postmenopausal patients with type 2 diabetes, which may provide caution on drug treatment in clinical practice. Whether TZD can protect male patients against BMD loss or not awaits further research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00774-009-0104-4DOI Listing
March 2010