8 Endocrinology and Metabolism

8 Endocrinology and Metabolism

2015046 Exp ressions of advanced glycosylation end p roducts in skin of diabetic m ice and their in fluence on collagen fibers.YANG Shengu（楊圣菊），et al. Dept Dermatol&Venereol，Affil Hosp，Nantong Univ，Nantong 226001.Chin J Dermatol 2014；47（11）：785-789.

ObjectiveTo investigate the expressions of advanced glycosylation end products（AGE）in skin ofmice with diabetesmellitus（DM）for different durations，and to evaluate their influence on collagen fibers.M ethodsForty healthy 8-week-old male C57BL/6Jmice were divided into DM group（n=20）and control group（n= 20）to receive multiple intraperitoneal injections of low dose streptozotocin（50 mg/kg）and citric acid buffer（0.1 mol/L），respectively，for5 consecutive days.Ten mice were sacrificed in each group on week 4 and 12 respectively after the last intraperitoneal injection，and full-thickness skin tissue sampleswere harvested from the middorsal region of each mouse.Then，hematoxylin-eosin（HE）staining was performed to observe histological changes，and total collagen content was estimated according to hydroxyproline content measured by an alkaline-hydrolysismethod.The cross-linking degree of collagen was determined by Edman degradation method using pepsin，themRNA expression level of collagen typeⅠandⅢby real-time quantitative PCR，the content of AGE by fluorospectrophotometry and Western blotting，and the level ofmalondialdehyde（MDA）by using a thiobarbituric acid method.Statistical analysis was carried out by t test.ResultsAs lightmicroscopy showed，the skin became obviously thinner in the diabeticmice with a progressive decrease in the number of collagen fibers in comparison with the controlmice.On week 4 and 12 after the last injection，the diabeticmice exhibited a significant reduction in the content of hydroxyproline（（684.5±76.7）vs.（787.7±87.7）mg/g，（558.1±73.1）vs.（757.8±75.3）mg/g，both P＜0.01）and in the levels of cross-linked collagen as well asmRNA expressions of collagenⅠandⅢ（P＜0.01 or 0.05），but a significant increase in the content of AGE（（37.47±10.65）vs.（26.39±3.74）AUF/mg hydroxyproline，（47.70±5.66）vs.（29.91±6.50）AUF/mg hydroxyproline，both P＜0.01）and MDA（（6.62±0.47）vs.（4.82±0.56）μmol/L，（8.63± 0.36）vs.（5.15±0.46）μmol/L，both P＜0.01）in skin tissue，compared with the controlmice.The level of non-cross-linked collagen in skin tissuewasalso lower inthe diabetic mice than in the control mice on week 12（P＜0.05）.Moreover，the contents of hydroxyproline and the expression levels of collagenⅠin skin were significantly lower（P＜0.05），but the levels of AGE and MDA were significantly higher（P＜0.01）in the diabetic mice on week 12 than in those on week 4.ConclusionThe characteristics of collagen fibers in skin are altered in diabetic mice when compared with normal control mice，which may be associated with increased AGE content and oxidative injury in skin.

（Authors）

2015047 Association between sedentary life style and risks of m etabolic synd rom e and diabetesm ellitus type 2.YE Ying（葉鶯），et al.Dept Noncommunicable Chronic Dis Contr&Prev，F(xiàn)ujian Dis Contr& Prev Center，F(xiàn)uzhou 350001.Chin JEpidemiol2014；35（11）：1235-41.

Ob jectiveTo explore the association of sedentary life style with risk ofmetabolic syndrome（MS）and diabetesmellitus type2（T2DM）.MethodsA total of6 016 local residents aged 18 years or older in Fujian province were recruited by multi-stage stratified cluster sampling method in 2010-2011.Data，including demographic information，physical activity and sedentary time were collected.Indices related to height，weight，waist circum ference，blood pressure and blood lipid were determined while MS and T2DM were diagnosed by IDF（2005）and WHO（1999）criteria.Logistic regression was used to estimate the correlations between sedentary behavior and MSor T2DM.Resu ltsThe prevalence rates of MSand T2DM were 19.0%and 8.0%respectively，in local residents aged 18 years or older，in Fujian province.The overall rate of sedentary behaviorwas18.1%，with the mean sedentary time as 4.3 hours.Both data showed significantly differences（P＜0.001）among control group，MS without T2DM group，MS with T2DM group and T2DM without MS group.Compared with the group of sedentary time＜2.0 h/d，1）the group with 2.0 -3.5 h/d was significantly correlated with MT group（OR=1.44，95%CI：1.03-2.03，P＜0.05），2）groups of 3.5-6.0 h/d and≥6.0 h/d were significantly correlated with M，T，MT group，respectively（OR：1.49-1.76 and 1.28-1.58 respectively，95%CI： 1.19-2.45 and 1.02-2.23 respectively，P＜0.05），and 3）sedentary behavior was independently associated with an increased risk of MT group（OR=1.82，95% CI：1.33-2.48，P＜0.01）and M group（OR=1.43，95%CI：1.14-1.78，P＜0.01），after the adjustment for factors as age，sex，cigarette smoking，alcohol drinking，BMI，education，occupation，sedentary behavior/ sedentary time.ConclusionMS and T2DM were associated with sedentary lifestyle，but these findings should be confirmed through further longitudinal studies.

（Authors）

2015048 Association of serum uric acid with metabolic syndrome and its com ponents.HU Ying（胡穎），et al.Dept Endocrinol，Affil Hosp，Guiyang Med Coll，Guiyang 550004.Chin JEndocrinol Metab 2014；30（9）：765-768.

Ob jectiveTo explore the association of serum uric acid（UA）withmetabolic syndrome（MS）and its components.M ethodsA total of 1 512 inhabitants aged 20 years old and above in Zhaiji community of Guiyang urban areas were investigated from November 2009 to February 2010 by adopting stratified cluster samplingmethod（634 males and 878 females）.All subjects were asked to fulfill the questionnaires and to measure the height，weight，waist circumstance（WC），and blood pressure；and to undertake oral glucose tolerance test.Venous blood sampleswere drawn tomeasure UA，fasting plasma glucose，2 h postprandial plasma glucose，triglyceride（TG），total cholesterol，high density lipoprotein cholesterol，low density lipoprotein cholesterol，and fasting insulin.Results（1）Age，bodymass index（BMI），WC，TG，and blood pressure，and homeostasismodel assessment of insulin resistance（HOMA-IR）increased with UA（all P＜0.05）.（2）UA was positively associated with the risk of MS（P＜0.05）.After adjusting for age，sex，BMI，waist-to-hip ratio（WHR），and HOMA-IR，the risk of MS in individuals with the highest uric acid quartiles was significantly increased compared to those with the lowest quartile（OR=2.86，95%CI 1.70-4.84，P＜0.05），and this finding was especially evident in females（OR=2.80，95%CI 1.51-5.17，P＜0.05）.（3）UA was strongly related to WC（OR=1.76，95%CI0.95-3.27，P＜0.05），blood pressure（OR=1.66，95%CI1.13-2.43，P＜0.05），and TG（OR= 2.80，95 CI 1.97-3.96，P＜0.05）after adjustment for age，sex，BMI，WHR，and HOMA-IR.ConclusionThe prevalence of MS increased with UA.Higher UA levelmay be an independent risk factor of MS.

（Authors）

2015049 11β-hydroxysteriod dehydrogenase and S100A16 co-regulate differentiation of 3T3-L1 adipocytes.LI LU（李璐），et al.Dept Gerontol，1st Affil Hosp，Nanjing Med Univ，Nanjing 210029.Chin JEndocrinolMetab 2014；30（9）：779-785.

ObjectiveTo investigate the synergistic effect of 11 β-hydroxysteriod dehydrogenase（11β-HSD1）and S100A16 on the differentiation of 3T3-L1 preadipocytes and itsmechanism.MethodsLentiviral vectors PLJM1-11β-HSD1 and PLJM1-S100A16-GFP were respectively constructed and co-transfected into 3T3-L1 preadipocytes.The cell strains expressing 11β-HSD1/S100A16 were screened with 2.5μg/ml puromycin for twoweeks. Western blotwas employed to verify the lentiviral carrier transfection effects.The expressions ofmarker genes related to the adipocyte differentiation were detected by means of realtime PCR.Oil red O staining was used to observe the lipid droplet accumulation and the content of triglyceride was measured after differentiation of preadipocytes.The effect of 11β-HSD1 and S100A16 on PPARγpromoter activity was detected by luciferase reporter gene.ResultsCompared with the empty vector group，the expressions of 11β-HSD1 and S100A16 protein in the lentivirus cotransfected 3T3-L1 cell strain were significantly higher.After3T3-L1 cell strain co-expressing 11β-HSD1 and S100A16 was induced to differentiate for 8 days，the lipid droplets accumulation and triglyceride content were siginificantly increased，along with increased expressions of adipocyte differentiation marker genes such as PPARγ，CCAAT/enhancer binding proteinα，lipoprotein lipase，fatty acid synthase，and adipocyte fatty acid-binding protein，in comparison with 11β-HSD1 or S100A16 overexpression.The result of reporter gene indicated that11β-HSD1/S100A16 enhanced PPARγpromoter activity.Conclusion11β-HSD1 and S100A16 may jointly promote the differentiation of 3T3-L1 preadipocytes through a synergistic effect on PPARγ expression and play a critical role in the development of obesity.

（Authors）

2015050 Role ofβ-catenin signaling pathway in the epithelial tom esenchymal transition induced by parathyroid horm one in renal tubu lar epithelial cells.GUO Yunshan（郭云珊），et al.Dept Nephrol，General Hosp，Jinan Milit Command，Jinan 250031.Chin J Nephrol，2014；30（10）：763-769.

Ob jectiveTo investigate the effect of parathyroid hormone（PTH）on the epithelial tomesenchymal transition（EMT）in human renal proximal tubular epithelial cells（HK-2 cells），and determine the role ofβ-catenin signaling pathway.M ethodsThe expression ofα-smooth muscle actin（α-SMA），E-cadherin andβ-catenin in HK-2 cells was measured by real-time PCR，Western blotting and immunofluorescence technique.The signaling pathway by which PTH activated EMT in HK-2 cells was identified by using syntheticβ-catenin siRNA.ResultsParathyroid hormone（10j-10mol/L）increasedα-SMA expression and decreased E-cadherin expression in HK-2 cells（P＜0.01，respectively）.Untreated cells showed the expression of E-cadherin，whereasα-SMA staining was noticeably increased in cells treated with PTH.β-catenin activity was significantly increased after exposed to PTH.Theα-SMA expression was decreased strongly and E-cadherin expression was increased afterβcatenin siRNA transfection（all P＜0.05）.ConclusionPTH significantly induces epithelial tomesenchymal transition in HK-2 cells throughβ-catenin signaling pathway.

（Authors）

2015051 Clinical im p lications of rearrangem ents during transfection of papillary thyroid cancer（RET/PTC）1，3 detected with FQ-PCR in fine-need le aspiration specimen of thyroid nodu les.YU Lingying（俞靈鶯），et al.Dept Endocrinol，1st People's Hosp，Hangzhou 310006.Chin J Endocrinol Metab 2014；30（10）：830-833.

Ob jectiveTo evaluate the clinical significance of rearrangements during transfection of papillary thyroid cancer（RET/PTC）1，3 in fine needle aspiration（FNA）specimen from regional thyroid nodules by FQ-PCR.M ethodsTwo hundred and eighty-five FNA sampleswere collected from patients with thyroid nodules during January 2012 to January 2013.RET/PTC1，3 rearrangements were detected with FQ-PCR.ResultsThe frequencies of the RET/PTC1 and RET/PTC3 rearrangements in 285 FNA samples were 17.2%（49/285）and 1.4%（4/ 285），respectively.During 21.7 months of follow-up，19（40.4%，19/47）RET/PTC1 positive patients were confirmed to have papillary thyroid carcinoma（PTC）after operation.In the patients with RET/PTC1 rearrangement PTC was found in Thy5 and Thy4 groups.In Thy 2 group，22.6%cases with RET/PTC1 rearrangements developed PTC as compared with 3.2%cases without it（χ2=6.667，P＜0.01）.In addition，8.5%（4/47）RET/PTC1 rearrangements emerged in benign lesions.ConclusionIt is convenient and reliable to detect RET/ PTC1，3 rearrangements by FQ-PCR using FNA samples.RET/PTC1 rearrangement frequently occurs in PTC，however it can be detected in benign lesions occasionally.

（Authors）

2015052 Effect of 17β-estradiol on proliferation of human thyroid stem cells.XU Shuhang（徐書(shū)杭），et al.Endocrinol Diabet Center，Jiangsu Prov Integr Chin &WestMed Hosp，Nanjing 210028.Chin JEndocrinol Metab 2014；30（9）：769-774.

ObjectiveTo investigate the effect of 17β-estradiol on the proliferation of thyroid stem/progenitor cells.M ethodsIn thyroid stem/progenitor cells derived from nodular goiters，the effects of 17β-estradiol on thyrosphere formation，estrogen receptor（ER）expression，cyclin D1 expression，and mitogen activated protein kinase（MPAK）pathway were analysed by BrdU ELISA，conventional and realtime PCR，immunofluorensence staining，and Western blot.Results17β-estradiol induced thyrosphere formation and proliferation of thyroid stem/progenitor cells.ER-αand ER-βwere expressed in thyroid stem and progenitor cells with higher mRNA expression level of ER-αcompared to differentiated thyrocytes（8.85±0.81 vs1.10±0.35，P＜0.01）.Stimulation by 1 nmol/L 17β-estradiol increased cyclin D1 mRNA expression and ERK phosphorylation levels， which was blocked by an ER antagonist，ICI 182780.ConclusionEstrogen stimulated the growth of stem cells derived from thyroid nodules via estrogen receptor，suggesting the relevance of increased thyroid stem cell proliferation with higher prevalence of thyroid nodules in women.

（Authors）

2015053 Effects of vitam in D supplementation on insu lin resistance in patientsw ith type 2 diabetesm ellitus.ZHOU Jie（周潔），et al.Dept Healthcare Endocrinol，Affil Shandong Prov Hosp，Shandong Univ，Jinan 250021.Natl Med JChina 2014；94（43）：3407-10.

Ob jectiveTo explore the effects of oral vitamin D supplementation on anthropometric parameters and insulin resistance（IR）in type 2 diabetesmellitus（T2DM）.MethodsA total of 164 subjectswith T2DM，aged 30-75 years，were randomly divided into two groups of intervention and control.The intervention group received a daily dose of 0.50μg calcitriol while the control group maintained the original treatment regimen.At the beginning and end of 12-week supplementation trial，the demographic and anthropometric datawere recorded and the serum levels of glucose，insulin，HbA1C and 25（OH）D measured.IR was assessed by the homeostasismodel approximation index.Resu ltsThere was no significant inter-group difference at baseline.Compared with the baseline level，bodymass index（BMI）（（-0.7±1.7）vs（-0.4±1.4）kg/m2）（P＜0.05），waist circumference（WC）（（-1.3±1.3）vs（-0.2±1.1）cm）（P＜0.05），fasting plasma glucose（FPG）（（-1.2± 2.3）vs（-0.6±2.8）mmol/L），fasting plasma insulin（FPI）（（-1.6±2.2）vs（-0.32±1.49）μU/m l）（P＜0.05），HbA1C（（-0.1±0.6）vs（-0.03± 0.94））（P＜0.05），HOMA-IR（（-0.91±2.63）%vs（-0.15±1.78）%）（P＜0.05）and 25（OH）D（（20±17）vs（1.0±3.3）ng/ml）（P＜0.05）decreased obviously in the intervention group at the end of study.After stratifying by different baseline serum levels of 25（OH）D，HOMA-IR significantly decreased after supplementation in＜20 ng/ml group（（6±3）vs（5± 3））（P＜0.05），20-30 ng/m l group（（6±3）vs（5± 3））（P＜0.05）and？30 ng/ml group（（5±3）vs（4±3））（P＜0.05）.And BMI（（26±6）vs（26±4）kg/m2）（P＜0.05），WC（（84±11）vs（82±12）cm）（P＜0.05），F(xiàn)PG（（8±4）vs（6±4）mmol/L）（P＜0.05），F(xiàn)PI（（17±4）vs（16±4）μU/ml）（P＜0.05）and HbA1C（（7.4±0.9）%vs（7.0±1.2）%）（P＜0.05）decreased statistically significant only in 15-20 ng/ml group.Multivariate regression analysis showed that HOMA-IR was a significant independent risk factor of 25（OH）D（OR=13，95%CI=4-39，P＜0.05）.ConclusionThere is significant improvement in BMI，WC，F(xiàn)PG，F(xiàn)PI，HbA1C and HOMA-IR after supplementation.Thus vitamin D supplementation may reduce insulin resistance in T2DM.

（Authors）

2015054 Correlation of secreted protein acidic and rich in cysteinew ith diabetic nephropathy.LILei（李磊），et al.Dept Endocrinol Metab，2nd Affil Hosp，Harbin Med Univ，Harbin 150086.Chin J Endocrinol Metab 2014；30（9）：741-746.

ObjectiveTo investigate the serum concentrations of secreted protein acidic and rich in cysteine（SPARC）in patients with diabetic nephropathy and SPARC mRNA and protein expressions in renal tissue of db/db mice.MethodsSerum SPARC levels in normal subjects and patients with type 2 diabetes mellitus（without diabetic nephropathy），chronic renal failure（without diabetes mellitus），and diabetic nephropathy were determined with enzyme-linked immunosorbent assay.RT-PCR，Western blot，and immunofluorescence were used to detect themRNA and protein expressions of SPARC in renal tissue of db/db mice.Resu ltsThe serum level of SPARC in diabetic nephropathy group was significantly higher than those in normal group，type 2 diabetesmellitus，and chronic renal failure group［（5.78±1.41 vs 3.58±0.41，4.51±1.08，and 3.81±1.16）μg/L，P＜0.05 or P＜0.01］.The SPARC level in the type 2 diabetesmellitus group was higher than that in normal group（P＜0.05），but there was no difference between normal group and chronic renal failure.SPARC mRNA and protein levels in renal tissue of db/db mice were higher compared with the littermates（P＜0.05）.ConclusionThe long term hyperglycemic state in patients with diabetic nephropathy causes pathological change of renal tissue.Simultaneously，increased secretion of SPARC from renal tissue results in elevation of serum SPARC level and may play a role in pathological change of diabetic nephropathy.

（Authors）

2015055 The relationship between the level of serum chem erin and m etabolic synd rom e.YUAN Guoyue（袁國(guó)躍），et al.Dept Endocrinol，Affil Hosp，Jiangsu Univ，Zhenjiang 212001.Chin JDiabetes2014；22（11）：961-965.

Ob jectiveTo investigate the relationship between the levels of serum chemerin and metabolic syndrome（MS）.Methods264 subjects were divided into MS group（n=117），non-MS group（n=57），and normal controls（NC）group（n=90）.All the subjects were divided into three subgroups：Terl，Ter2 and Ter3 according to the levels of serum chemerin.A 75 g OGTT and insulin releasing testwere performed.Meanwhile，blood lipid，serum chemerin，hsC-RR and other items were measured.ResultsThe serum chemerin was higher in MSgroup than in non-MSgroup and NC group.The level of BMI，WC，WHR，SBP，F(xiàn)PG，2 hPG，HbA1c，F(xiàn)INs，HOMA-IR，TG was in turn increased from Ter1 to Ter3 Subgroup，the level of hsC-RP and the prevalence of MS were in turn increased，while HDL-C was decreased（P＜0.05）.Chemerin was positively correlated with BMI，WC，WHR，SBP，F(xiàn)PG，2 hPG，HbA1c，F(xiàn)Ins，2 hIns，HOMA-IR，TG and hsC-RP（P＜0.05），and negatively correlated with HDL-C，HOMA-β（P＜0.01）.Logistic regression analysis showed serum chemerin was positively associated with MS（OR=2.197，P＜0.01）.The area under ROC curve suggested that MS-predicting chemerin cut-offpointwas serum chemerin 72.4 ng/m l.ConclusionSerum chemerin is associated with the occurrence of MS and might be an independent predictor of MS.

（Authors）

2015056 Effect of angiopoietin-1 on exp ression of PEDF and TSP-1 in kidney of diabetic rats.QIU Zhicheng（裘志成），et al.Dept Nephropathy，Affil Hosp，Zunyi Med Coll，Zunyi563003.Chin JDiabetes 2014；22（11）：1034-37.

ObjectiveTo observe the expressions of throm-bospondin-1（TSP-1）and pigment epithelium-derived factor（PEDF），and investigate the effect of recombinant adenovirus angiopoietin-1（Ang-1）on these factors in renal tissue of diabetic rats.MethodsRatmodel of diabetic nephropathy was induced by a single intraperitioneal injection of STZ.The subjectswere divided into four groups：control（NC）group，DN group，blank vector（BV）group and Ang-1 treated（AV）group.The urinary protein was observed at 8th，12th，20thand 28thweek. The expression levels of protein and mRNA of PEDF，TSP-1 renal tissue at the same time points were detected by immunohistochemistry and real-time PCR.Results24 hUA1b in DN，BV and AV groups were higher than those in NC group，but increased 24 hUA1b in AV group was decreased after 20thweek（P＜0.05）.Immunostaining score and PEDF mRNA level in DN，BV and AV groupswere decreased，and TSP-1 was increased as compared with NC group（P＜0.05）.In AV group，decreased protein and mRNA levels of PEDF were upregulated，and increased TSP-1 was downregulated after 12thweek，as compared with DN or BV groups（P＜0.05）.ConclusionThe abnormal expression of TSP-1 and PEDF may play a role in the development of DN.Ang-1 administration can improve abnormal levels PEDFand TSP-1 in kidney of diabetic rat.

（Authors）

2015057 Effect of atorvastatin on serum paraoxonase-3 levels in new ly diagnosed type 2 diabetesmellitus patientsw ith carotid atherosclerosis.LIU Yuntao（劉云濤），et al.Dept Endocrinol，Renhe Hosp，China Three Gorges Univ，Yichang 443000.Chin J Diabetes 2014；22（11）：978-983.

Ob jectiveTo investigate the effect of atorvastatin on serum paraoxonase-3（pon3）level in newly diagnosed T2DM patients with carotid atherosclerosis（CAS）.Methods87 newly diagnosed T2DM patients with CAS were divided into atorvastatin treated group（n=43）and fenofibrate treated group（n=44）.45 healthy individuals with normal glucose tolerancewere selected as the control（NGT group）.Serum pon3 level was measured by ELISA method.The association between serum pon3 levels and FPG，F(xiàn)Ins，HbA1c，BMI，HOMA-IR，homocysteine（Hcy），fibrinogen（FIB），hsC-RP，superoxide dismutase（SOD）and carotid intima-media thickness（CIMT）were also analyzed.Serum pon3 levels were observed in newly diagnosed T2DM patients with CAS before and after treatment.Results（1）Atorvastatin and fenofibrate group had significantly higher serum pon3 levels than NGT group（3.55±0.54）ng/ml，（3.61± 0.51）ng/m l vs（2.27±0.46）ng/m l，（P＜0.01），respectively.（2）Pearson correlation analysis showed that serum pon3 levelwas positively correlated with BMI，F(xiàn)Ins，LDL-C，HOMA-IR，hsC-RP，F(xiàn)PG，HbA1c，Hcy，F(xiàn)IB and CIMT（r=0.545，0.547，0.520，0.529，0.572，0.635，0.624，0.542，0.517，0.525，P＜0.05 or P＜0.01，respectively），and was negatively correlated with HDL-C，SOD（r=-0.565，-0.566，P＜0.05）.（3）After 24 weeks treatment，serum pon3，SOD and HDL-C levelswere significantly increased（P＜0.05），while TC，TG，LDL-C，CIMT，Hcy，F(xiàn)IB，hsCRP levels were significantly decreased in atorvastatin group（P＜0.05），and fenofibrate group had no significant difference of lipid profiles compared with atorvatatin group，while CIMT，Hcy，F(xiàn)IB，SOD，serum pon3 and hsC-RP levels have no significant difference.（4）Multiple stepwise regression analysis showed that CIMT，HOMA-IR，Hcy and FIB were the independent related factors influencing the serum pon3 level of T2DM patients，and HOMA-IR，F(xiàn)IB，Hcy，pon3 were the independent related factors influencing CIMT of the newly diagnosed T2DM patients with CAS.ConclusionAtorvastatin can decrease the CIMT of newly diagnosed T2DM patients with CAS.This role is associated with the increase of serum pon3，which is independent of its effects on reducing lipid.

（Authors）

2015058 Efficacy and safety observation of liraglutide and insulin as combination therapy in the treatment diagnosed type 2 diabetesw ith obesity.ZHANG Ping（張萍），et al.Dept Endocrinol，2nd Affil Hosp，AnhuiMed Univ，Hefei230601.Chin JDiabetes2014；22（11）：974-977.

ObjectiveTo assess the efficacy and safety of liraglutide and insulin as combination therapy in the treatment of newly diagnosed type 2 diabetes with obesity.MethodsA 16-week，randomized，parallel-group studywas carried out.A total of 76 patients who had completed the trialwere randomly assigned to either the liraglutide-added group（the observation group）or the group of insulin combined with metformin only（the controll group）.Efficacy and adverse reactions were evaluated.Resu ltsAfter intervention，glycated hemoglobin A1c（HbA1C）［the control group（10.94±1.55）%vs（6.90±0.75）%，the observation group（11.41± 1.43）%vs（5.86±0.76）%］and insulin resistance index（HOMA-IR）［the control group（3.40±0.63）vs（2.0±0.35），the observer group（3.38±0.66）vs（1.60±0.54）］decreased significantly，while homeostatic model assessment of the insulin secretion index（HOMP-β）［the control group（13.34±4.07）vs（33.56±7.06），the obser-ver group（12.53±3.25）vs（49.88±10.58）］（P＜0.05）increased significantly in all two groups（all P＜0.05）；The body mass index（BMI）decreased significantly in observation group（28.89±1.19）vs（26.58±0.93）kg/m2；The HbA1c（6.90±0.75）%vs（5.86±0.76）%and the HOMAIR（2.00±0.35）vs（1.60±0.54）decreased further in observation group when compared with the control group，while the HOMA-βwas significant higher（33.56±7.06）vs（49.88±10.58）（P＜0.05）.The incidence of hypoglycemia was higher in the observation group when compared with the control group（81.6%vs 72.1%）（P＜0.05）.Serious hypoglycemia did not happen in the two groups.ConclusionThe treatment of Adding liraglutide to insulin in newly diagnosed type 2 diabetes with obesity can induce a significant reduction in blood glucose and body weight，and improve function ofβ-cell.Serious adverse reactions haven't been found.

（Authors）

2015059 The relationship between abdom inal obesity and new-onset hyperuricem ia in diabetic population.LIU Xing（劉星），et al.Dept Phy Exam Center，Affil Kailuan General Hosp，Hebei United Univ，Tangshan 063000.Chin JDiabetes 2014；22（11）：970-973.

ObjectiveTo explore the relationship between abdominal obesity and new-onset hyperuricemia in diabetic population.M ethodsA total of 5122 diabetic patients without history of hyperuricemia who had participated in the health examination between 2006 and 2007 were selected as the observation cohort in this prospective cohort study.The observation population was divided into obesity group and non-obesity group according to their waist circumference.The incidence of newly-onset hyperuricemia in the health examination from 2010 to 2011 was compared between obesity and non-obesity groups.The relationship between abdominal obesity and new ly-onset hyperuricemia was analyzed by multiple logistic regression analysis.Results（1）The average follow-up time of subjects was（48.9±5.6）months.The incidence of hyperuricemia was 5.6%（285/5122）.The incidence of HUA was higher in obesity group than in non-obesity group（6.9%vs3.8%，P＜0.01）；（2）Multiple logistic regression analysis showed that abdominal obesity，sex，SBP，the baseline uric acid were the effective factors for newly-onset hyperuricemia，and the obesity was independent risk factors（OR=1.44，95%CI：1.09-1.89）.ConclusionAbdominal obesity may be an independent risk factor of the new-onset hyperuricemia in diabetic patients.

（Authors）

2015060 The effects of calcitriol on am eliorating podocytes impairment and its possiblemechanism in DN rats.SONG Zhixia（宋志霞），etal.Instit Nephrol，Zhongda Hosp，Southeast Univ Med Sch，Nanjing 210009.Chin JNephrol 2014；30（10）：777-783.

ObjectiveTo investigate the effects and underlying mechanism of calcitriol on ameliorating podocytes impairment in DN rats.M ethodsSD rats were randomly divided into four groups：normal control（NC）group，calcitriol treatment（VD）group：calcitriol 0.1μg·kg-1· d-1，diabetic nephropathy（DN）group：streptozocin（STZ）58 mg/kg，DN treated with calcitriol（DN+VD）group：calcitriol 0.1μg·kg-1·d-1+STZ 58 mg/kg. Rats were sacrificed at the end of 18 weeks.ResultsCompared with the DN group，the DN+VD group exhibited significantly lower proteinuria by 36%，improved renal histology at the end of the experiment（P＜0.05），and similar levels of blood glucose，serum urea nitrogen aswell as body weight（P＞0.05）.There were no significant differences in the serum concentrations of creatinine，calcium and phosphorus among the four groups（P＞0.05）.In DN group，the expressions of nephrin，podocin，VDR，PI3K-p85 and p-Akt were significantly decreased and the expression of desmin was increased compared to NC group.Calcitriol treatment could attenuate the above changes.Additionally，a positive correlation was observed between the expressions of nephrin and VDR（r=0.776，P＜0.05）.Likewise，the expression of nephrin was positively correlated with either PI3K-p85 or p-Akt（r=0.736，r=0.855，all P＜0.05）.ConclusionCalcitriol can ameliorate podocytes injury in DN rats，which might be related with the further up-regulation of PI3K/p-Akt signaling pathway.

（Authors）

2015061 Effect of combined excess-iodine and lowp rotein diet on grow th，m etabolism and m orphological changes in thyroid of W istar rats.BIAN Jianchao（邊建朝），et al.Shandong Endemic Dis Prev&Contr Instit，Jinan 250014.Chin J Endemiol 2014；33（5）：511-516.

ObjectiveTo establish an animalmodel of high-iodine and low-protein in Wistar rats，and to observe the effect of combined excess-iodine and low-protein diet on growth，metabolism and morphological changes in thyroid.MethodsAccording to bodyweight［（110±10）g］and sex（half male and half female），one hundred and ninety-two Wistar rats，1 month afterweaning，were randomly divided into①normal iodine control group（NI），②10-fold excess-iodine group（10HI），③50-fold excessiodine group（50HI），④100-fold excess-iodine group（100HI），⑤low-protein control group（LC），⑥low-protein and 10-fold excess-iodine group（L10HI），⑦lowprotein and 50-fold excess-iodine group（L50HI），⑧l(xiāng)owprotein and 100-fold excess-iodine group（L100HI）. Twenty-four ratswere in each group，with the experimental period of 6 months.The iodine content of NIand LC groupswas 4.65μg/d；10HI，50HI and 100HI groups were 46.50，232.50 and 465.00μg/d，respectively. The animal's body weight，water and food consumption were recorded weekly.At the end of60，120，180 days，urine and blood sampleswere collected from eight rats in each group.Urinary iodine was tested by arseni cerium catalytic spectrophotometry；serum iodine was tested by the method of chloric acid.Histological change of the thyroid gland was observed by transmission electron microscopy and hematoxylin-eosin（HE）staining at the end of 6 months；apoptosis of thyroid was tested by terminaldeoxynucleoitidyl transferase mediated nick end labeling（TUNEL）method.ResultsAt the end of 4，8，16，18，22 and 24 weeks，the differences of bodymass of rats among groups were statistically significant（F=4.26，3.75，4.98，4.09，3.28，3.95，all P＜0.05）.At the end of60，120，180 days，the differences of iodine concentration in urine and blood among groupswere statistically significantly（H=5.37，6.03，all P＜0.05）. Lightmicroscopy showed that thyroid follicular epithelial cells became flattened，and follicles became distended with colloid following increasing of iodine concentration. Electron microscopy showed increased glial vesicles，condensation of nuclear chromatin，karyopyknosis，and karyolysis with increasing of iodine concentration.The differences of apoptotic indexes among groupswere statistically significant（F=4.59，P＜0.01）.The apoptotic indexes of L50HI and L100HI groups［（21.50± 5.20）‰］were higher than those of 50HI and 100HI groups［（11.20±4.30）‰，（19.40±4.80）‰，P＜0.01 or＜0.05］.ConclusionExcessiodine and lowprotein can cause growth retardation，abnormal iodine metabolism，and thyroid follicular epithelium damage in Wistar rats.

（Authors）

2015062 A correlation study between serum direct bilirubin and lipid in type2 diabetic patients.WANG Ru（王茹），et al.Dept Endocrinol，Chin PLA General Hosp，Beijing 100853.Chin J Intern Med 2014；53（10）：783-787.

ObjectiveTo investigate the association between DBil with normal range and serum lipid in type 2 diabetic patients.M ethodsA total of 979 subjectswith type 2 diabetes admitted to the Department of Endocrinology of Chinese PLA General Hospital from June 2012 to June 2013 were included for the study.Serum DBil，TC，TG，HDL-C and LDL-C levels were collected for the analyses.Subjectswere divided into four groups based on the DBil levels：Q1 group（＜2.2μmol/L），Q2 group（2.2 -＜2.9μmol/L），Q3 group（2.9-＜3.9μmol/L）and Q4 group（≥3.9μmol/L）.Resu lts（1）TC，TG，LDL-C levels were significantly lower in Q4 group thanthose in the other three Q groups after adjustmentof age，gender，duration of diabetes，BMI，smoking，drinking，glycosylated hemoglobin A1c（HbA1c），fasting plasma glucose（FPG），medication，ALT，AST and fatty liver. No difference could be viewed in HDL-C level between each group（P=0.65）.（2）Pearson correlation analyses showed that DBil was inversely correlated with TC（r= -0.33，P＜0.01），TG（r=-0.23，P＜0.01），LDLC（r=-0.18，P＜0.01），and positively correlated with HDL-C level in men（r=0.14，P＜0.01），respectively.Multiple linear regression analyses showed DBil was an independent impact factor for TC，TG and LDLC.（3）Compared with Q1 group，the odds ratio（OR）for dyslipidemia was 0.54（95%CI 0.35-0.82，P＜0.01），0.56（95%CI 0.37-0.85，P＜0.01）and 0.44（95%CI 0.29-0.69，P＜0.01）in Q2，Q3 and Q4 group，respectively，after age，gender，duration of diabetes，BMI，smoking，drinking，HbA1c，F(xiàn)PG，medication，ALT，AST and fatty liverwere adjusted.Moreover，the OR for dyslipidemia wasmuch lower in Q4 man subjectswith age＜55 years，HbA1c≥6.5%，BMI＜25 kg/m2，and with no fatty liver.ConclusionDBil in normal range was closely associated with lipid profile in type 2 diabetes.Itmight play a protective effect in dyslipidemia.

（Authors）

2015063 Reactive oxygen species inhibition improves the down-regulation of adiponectin in 3T3-L1 adipocytes induced by AGEs.LIN Ning（林寧），et al. Dept Endocrinol，Xinhua Hosp，Shanghai Jiaotong Univ Med Sch，Shanghai 200092.Chin J Endocrinol Metab 2014；30（10）：844-848.

Ob jectiveTo investigate the effects of reactive oxygen species（ROS）inhibition on the downregulation of adiponectin（ADPN）inmouse 3T3-L1 adipocytes by advanced glycation end-products（AGEs）.MethodsAGEs were prepared for incubating with cell.3T3-L1 preadipocytes were cultured in vitro and differentiated intomature adipocytes.Cell differentiation and lipid accumulation were determined by oil red O staining.After being intervened with AGEs，2′，7′-dichlorofluorescein diacetate（DCFH-DA）was used as a reactive oxygen species（ROS）capture agentand the fluorescent intensity of2′，7′-dichlorofluorescein（DCF）was detected by flow cytometry.Adiponectin expression under AGEs in 3T3-L1 adipocytes pretreated with N-acetyl-L-cysteine（NAC）or not was detected by real-time fluorescent PCR and ELISA.ResultsThe level of ROS in 3T3-L1 adipocytes treated with AGEs was increased.mRNA and protein of ADPN were down-regulated.After inhibition with ROS，mRNA and protein expressions of ADPN injured by AGEs were ameliorated.ConclusionExposure of3T3-L1 adipocytes to AGEs induces oxidative stress in vitro，which decreases the expression of ADPN，and causes functional impairment of adipose cells and insulin resistance.

（Authors）

2015064 Effects of active and passive smoking on chronic kidney disease in patients with type 2 diabetesmellitus.JIANG Fei（蔣菲），etal.ShanghaiDiabetes Instit，Shanghai Clin Diabet Center，Shanghai 200233.Chin J Intern Med 2014；53（11）：858-864.

ObjectiveThis study aimed to assess the effects of active and passive smoking on chronic kidney disease（CKD）in patients with type 2 diabetes mellitus（T2DM）.M ethodsSeven hundred and five patients with T2DM were recruited in the study and were divided into three groups based on smoking status as active smokers，passive smokers and non-smokers.Twenty-four hour urinary albumin excretion（24hUAE）wasmeasured，and estimate glomerular filtration rate（eGFR）was calculated with age and blood creatinine levels.Results（1）The proportion of CKD in T2DM in the present study was 31.63%（223/705）with 28.6%（22/77），30.0%（15/50）and 29.6%（73/247）for non-smokers，passive smokers and active smokers in men，and 29.9%（40/134），35.9%（66/184）and 7/13 for non-smokers，passive smokers and active smokers in women，respectively.In comparison with non-smokers，a higher risk of CKD was found in both passive and active smokers（OR=1.07 and OR=1.05 in men；OR=1.31 and OR=2.74 in women，respectively）.（2）Compared with non-smokers，passive smokers had a significant higher risk for albuminuria in women（OR=2.02，P=0.016）.（3）After adjusting for gender，age，duration of T2DM，BMI，systolic blood pressure，glycosylated hemoglobin A1C and lipids，therewas a significant decrease in eGFRbetween active and never smokers（P=0.018）or passive smokers（P=0.000）in women.No differences could be found in eGFR between each smoking status in men.ConclusionSmoking exposure alone confers a high risk for CKD in patients with T2DM.Our results highlight an importance in implementation of a smoke-free environment for patients with T2DM.

（Authors）

2015065 Effects of hyperparathyroidism patients'serum and klotho p rotein on the apop tosis of human umbilical vein endothelial cells.CHEN Cheng（陳鋮），et al.Dept Nephrol.1st Affil Hosp，Nanjing Med Univ，Nanjing 210029.Chin JNephrol 2014；30（11）：856-862.

Ob jectiveTo investigate the effects and underlying mechanism of secondary hyperparathyroidism（SHPT）patients'serum and klotho protein on the apoptosis of human umbilical vein endothelial cells（HUVECs）.M ethodsThree types of mixed serum from 15 patients with SHPT（serum S），10 CKD stage 5 patients without SHPT（serum C）and 15 healthy volunteers（serum H）were collected.HUVECs were incubated with 10%serum H，10%serum C，10%serum S and 10%serum S plus klotho respectively.The apoptosis rate ofendothelial cells was evaluated by flow cytometry.The activity of Caspase-3 wasmeasured by spectrophotometry.The levels of AKT and phosphorylated forms of AKT（p-AKT）were detected by Western blotting（with or without PI3K/AKT inhibitor LY294002）.ResultsThe apoptosis of HUVECs was both induced by the serum S and serum C.The apoptosis rate was greater in serum S group than that in serum C group（P＜0.05）.The apoptosis was partly inhibited when klotho protein（50-100μg/L）was added（P＜0.05），accompanying the up-regulation of p-AKT.The above effects could be blocked by LY294002.The activity of Caspase-3 was up-regulated in SHPT group compared to healthy control group（P＜0.05）and the up-regulation could also be inhibited by klotho protein（P＜0.05）.ConclusionThe apoptosis of HUVECs is induced by the serum from CKD stage 5 patients without SHPT and SHPT patients.Klotho protein can protect the HUVECs from apoptosis by up-regulating p-AKT and inhibiting Caspase-3.

（Authors）