• Volume 40,Issue 7,2015 Table of Contents
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    • >百家争鸣
    • Prevention of cardiovascular risk factors in patients with diabetes mellitus in China from ADA guideline in 2015

      2015, 40(7):909-910.

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      Abstract:

    • Comparison on cardiovascular risk factor prevertion between 2015 AACE/ACE guideline and 2015 ADA guideline

      2015, 40(7):911-913.

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      Abstract:

    • Relationship between zinc-α2-glycoprotein and insulin resistance-related diseases

      2015, 40(7):914-917.

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      Abstract:With the development of modern lifestyle and alteration of eating habits,the core of disease spectrum has gradually turned into chronic non-infectious diseases. Cardiovascular disease,lipid metabolism disorders,obesity,metabolic syndrome,polycystic ovary syndrome are associated with insulin resistance in recent studies. Insulin resistance is an important part of chronic non-infectious dis-eases,which will seriously influence the quality of life. Zinc-α2-glycoprotein(ZAG) is a newly discovered adipocytokine. Because of its important role of weight controlling and insulin sensitivity improving,lots of clinical studies have been performed to prove the as-sociation between ZAG and insulin resistance diseases in recent years.

    • >追糖溯源
    • Telomere-telomerase system and unhealthy lifestyles in diabetes mellitus

      2015, 40(7):918-921.

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      Abstract:Unhealthy life style is one of the important risk factors for the occurrence and development of diabetes mellitus. Lots of re-searches indicate that telomere length and abnormal telomerase activity are associated with the development of diabetes mellitus and unhealthy life styles. We review the progress of clinical researches about the relationship between telomere-telomerase system and unhealthy life style in patients with diabetes mellitus.

    • Aging and type 2 diabetes mellitus

      2015, 40(7):922-925.

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      Abstract:Aging is an important risk factor for many metabolic disorders,including obesity,impaired glucose tolerance,and type 2 diabetes mellitus(T2DM). It is reported that the incidence of T2DM significantly increases with age. The relevance of this association is dramatically magnified by the concomitant global aging of the population. Insulin resistance and β-cell dysfunction play crucial roles in the age-related impairment of glucose homeostasis. It has great significance in clarifying the pathophysiology of T2DM. Understand-ing the relationship between aging and factors leads to impaired glucose homeostasis such as pancreatic β-cell mass,insulin secre-tion,insulin resistance.

    • STZ-induced paternal diabetes in rats contributes to insulin resistance in the aged offspring

      2015, 40(7):926-930.

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      Abstract:Objectives:To investigate the influence of paternal diabetes on insulin sensitivity of the aged offspring. Methods:Male SD rats were intraperitoneally injected with streptozotocin(STZ) and then mated with healthy female SD rats. Body weight,fed and fasting blood glucose were determined in the offspring. Hyperinsulinemic-euglycemic clamp was performed to assess insulin sensitivity in the aged offspring. Western blot was implemented to evaluate the following proteins:p-Akt,Akt,p-Irs and Irs in liver tissues. Oil red O staining and liver triglyceride(TG) analysis were employed to evaluate the liver tissues lipidosis. Results:Blood glucose levels in STZ-treated male rats(DM)(22.6 ± 1.32) mmol/L were significantly higher than that in control group(CT)(5.88±0.13) mmol/L(P=0.000). Body weight analysis showed that the body weight of 80-week-age offspring of paternal diabetic rats(DM-O)(652.0±10.7) g was significantly higher than that in the offspring of control group(CT-O)(598.0±11.9)g (P=0.003). Hyperinsulinemic-euglycemic clamp test showed that the glucose infusion rate was significantly lowered in aged DM-O(6.23± 0.30) mg/(kg·min) than in the CT-O(8.65±0.43) mg/(kg·min)(P=0.005 2). Western blot showed that p-Akt/Akt level in the aged DM-O(0.023 4±0.004 4) was significantly lowered than that in the CT-O(0.059 8 ± 0.011 0)(P=0.016),and p-Irs1/Irs1 level in the aging DM-O(0.255±0.031) was significantly lower than that in the CT-O(0.452±0.057)(P=0.016). Oil red O staining revealed that liver tissues lipidosis was more serious in the aged DM-O than in the CT-O. Liver TG content was significantly increased in the aged DM-O(86.2±10.2) mol/g,but was significantly lower than in the CT-O(61.10±4.71) mol/g(P=0.045 7). Conclusion:Paternal diabetes mellitus induces insulin resistance in the aged offspring,possibly caused by liver tis-sues lipidosis.

    • Effects of overexpression of prostate apoptosis response-4 on the NIT-1 cell

      2015, 40(7):931-934.

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      Abstract:Objective:To construct recombinant adenovirus vector containing PAR-4 gene,so as to lay a foundation for further study of the function of PAR-4 and to illuminate the effect of PAR-4 on islet β cell line-NIT-1. Methods:Oligo Designer 3.0 was used to de-sign the PCR primers:PRKC apoptosis WT1 regulator(pawr). Then,the gene fragments of pawr were obtained by RT-PCR and insert-ed into the ADV1 vector by restriction enzyme digestion.The recombinant vector plasmid pAdtrack-pawr-CMV was constructed,and then,the recombinant pAdTrack-pawr-CMV was linearized and translated into the competent bacteria with pAd-Easy-1 for homolo-gous recombination to obtain pAdTrack-PAR-4. NIT-1 cell was divided into 4 groups:low glucose control,low glucose+overexpression of PAR-4,high glucose control,high glucose + overexpression of PAR-4,and protein expression level was detected by Western blot,the proliferation ability by MTT,the secretion ability after glucose stimulation by ELISA. Results:The pawr genes were verified by gene sequencing. The recombinant plasmid was successfully extracted by high purity plasmid extraction median kit. The recombinant adenovirus vector plasmid with mono-restriction endonuclease enzyme was evaluated. The earliest expression of GFP was observed in HEK293 cells and after 48 h of amplification the CPE was observed and the final viral titer was 1×109 pfu/ml. The protein expression level of PAR-4 was significantly increased in low glucose+overexpression of PAR-4 group and high glucose+overexpression of PAR-4 group than in its control groups. Proliferation ability and insulin secretion were decreased in high glucose+overexpression of PAR-4 group than in low glucose+overexpression of PAR-4 group and high glucose control group. Conclusion:The over-expres-sion of PAR-4 group has higher expression of PAR-4. After transfection and culture by high glucose concentration,the pro-liferation ability of high-glucose cultured NIT-1 is decreased.

    • Relationship between alcohol intake and prevalence of diabetes mellitus:a cross-sectional study

      2015, 40(7):935-939.

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      Abstract:Objective:To investigate the relationship between alcohol intake and prevalence of diabetes mellitus(DM). Methods:Stratified sampling was used to select 4 000 permanent residents aged 40 years and above. All participants completed standardized questionnaire,physical examination and biochemical tests. Results:The total effective number was 3 970 and the prevalence of DM was 19.47%. The percentage of drinking was 41.2%,of which the male was 60.9%,the female was 30.9%;the percentage of male was significantly higher than that of female(P<0.05). The prevalence of newly diagnosed DM in small-amount drinking group(male 5.09%,female 4.26%) was lower than that of non-drinking group(male 9.17%,female 7.11%). The prevalence in large-amount drinking group(male 21.76%,female1 15.19%) was significantly higher than that of other three groups. The prevalence of previously diagnosed DM was decreased with the increase of drinking amount;the prevalence of large-amount drinking group was the lowest. In general,the prevalence of newly diagnosed DM in small-amount drinking group was lower than that of non-drinking group. The prevalence of large-amount drinking group was significantly higher than that of the other three groups. The prevalence of previously diagnosed DM in drinking groups was lower than that of non-drinking group. The levels of 2-hour postprandial glucose(2hPG) and hemoglobin A1C(HbA1C) in groups of small-amount and moderate-amount drinking groups were significantly lower than those of non-drinking group. In large-amount drinking group,the levels of fasting plasma glucose,2hPG and HbA1C were significantly higher than those of the other three groups;the level of cholesterol was significantly higher than that of small and moderate drinking group. The high-density lipoprotein was significantly lower than that of the other three groups,the low-density lipoprotein was significantly higher than that the other three groups(P<0.05). The multivariate logistic regression analysis revealed that the group of small-amount drinking had a lower odds ratio for diabetes compared with that of non-drinking group(OR=0.641,95%CI=0.508 to 0.807),and it was a protective factor for diabetes even after the adjustment of gender,age,BMI,smoking,calorie intake,family history of diabetes. Conclusion:Small-amount drinking is a protective factor for DM. Large-amount drinking can increase the levels of blood glucose and blood lipid.

    • Evaluation of islet autoantibodies and β-cell function in classification of patients with ketosis prone diabetes

      2015, 40(7):940-944.

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      Abstract:Objective:To investigate the clinical value of islet autoantibodies(A) and islet β-cell functions(a total of four kinds of combination:A+β+,A+β-,A-β+,A-β-)in the differential diagnosis and classification in patients with ketosis-prone diabetes(KPD). Methods:A total of 134 patients with newly diagnosed KPD were included,who were admitted to West China Hospital from January 2000 to December 2010. They were divided into four categorical groups based on the presence or absence of autoantibodies(A+ or A-) and β-cell functional reserve(β+ or β-):A+β+(n=15),A+β-(n=13),A-β+(n=77),A-β-(n=29). Islet autoantibodies includ-ing islet cell antibody,insulin autoantibody and glutamic acid decarboxylase antibody were measured. The clinical characteristics and biochemical parameters were compared among four groups. Results:Of the total 134 patients,there were differences in body mass in-dex(BMI),waist and hip circumference ratio(WHR),plasma glucose concentration,glycosylated hemoglobin A1c(HbA1c) and triglyc-eride(TG) in four groups(BMI:P=0.000;WHR:P=0.026;blood glucose:P=0.009;HbA1c:P=0.001;TG:P=0.044). BMI and WHR were significantly higher in patients of A-β+ than in patients of A-β-(BMI:P=0.005;WHR:P=0.004). Plasma glucose concentration and hemoglobin A1c (HbA1c) of patients in A-β+ group were lower than those of patients in A-β- group(plasma glucose concen-tration:P=0.036;HbA1c:P=0.010),but the triglyceride levels were significantly higher in A-β+ group than in A-β- group(P=0.015). Conclusion:Patients with KPD show significantly different levels of β-cell function,clinical and biochemical characteristics,which may need different therapeutic strategies. Aβ solution based on the autoantibodies(A) and β-cell functional reserve can provide ref-erences in the treatment of KPD.

    • >纸上说糖
    • Effect of XCT790 on MSCs apoptosis induced by serum deprivation,hypoxia and high glucose concentration

      2015, 40(7):945-950.

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      Abstract:Objective:To investigate the effects of XCT790 on bone mesenchymal stem cells(MSCs) apoptosis induced by hypoxia,serum deprivation and high glucose concentration. Methods:MSCs were divided into 5 groups:control group(cultrued under normal conditions) and 0-20 μmol/L XCT790 treatment groups(cultured under 3% O2,serum deprivation and 25 mmol/L glucose concentra-tion). The apoptosis rates were measured by Annexin V-APC /7-AAD on flow cytometry. The protein levels of Bcl-2 and Bax corre-lated with apoptosis were detected by Western blot. And the ratios of Bcl-2/Bax were calculated. Results:After being exposed to 5-20 μmol/L XCT790 for 24 h,the apoptosis rates of 5 μmol/L XCT790 treatment group(20.02±0.92)%,10 μmol/L XCT790 treatment group(26.04±1.24)% and 20 μmol/L XCT790 treatment group(50.73±3.55)% were significantly higher than of 0 μmol/L XCT790 treatment group(14.34±0.61)%,increasing in a dose-dependent manner(P<0.05). Western blot showed the expression of pro-apop-totic protein Bax in 5 μmol/L XCT790 treatment group(0.132 3±0.033 8),10 μmol/L XCT790 treatment group(0.140 8±0.006 8) and 20 μmol/L XCT790 treatment group(0.199 4±0.061 7) was significantly higher than that in 0 μmol/L treatment group(0.116 4±0.017 2),while the expression of anti-apoptotic protein Bcl-2 in 5 μmol/L XCT790 treatment group(0.069 7±0.013 2),10 μmol/L XCT790 treatment group(0.051 2±0.005 6),20 μmol/L treat-ment group(0.041 3±0.005 5) was significantly lower than that in 0 μmol/L treatment group(0.092 3±0.021 3). The Bcl-2/Bax ratios of 5 μmol/L XCT790 treatment group(0.530 7±0.027 9),10 μmol/L XCT790 treatment group(0.397 9±0.034 2) and 20 μmol/L XCT790 treatment group(0.234 8±0.032 1) were significantly lower than that in 0 μmol/L XCT790 treatment group(0.851 7±0.084 4),decreasing in a dose dependent manner(P<0.05). Conclusion:In the conditions of hypoxia,serum deprivation and high glucose concentration,antagonism of estrogen-related receptor α makes MSCs apoptosis rates increase significantly as Bcl-2/Bax ratios decrease,which indicates that ERRα plays an important role in preventing MSCs apoptosis.

    • Differentiation of insulin-secreting cells derived from human embryonic stem cells induced by LY294002 or Exendin-4 in vitro

      2015, 40(7):951-954.

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      Abstract:Objective:To investigate whether adding different inducible factors:phosphatidylinositol 3-kinase(PI3K) inhibitor LY294002 and long-acting glucagon-like peptide-1(GLP-1) mimetic Exendin-4 could efficiently induce human embryonic stem cells(HESc) to differentiate into mature insulin-producing cells. Methods:A five-stage culturing strategy was used in this study. Human embryonic stem cells were amplified in vitro for 6-7 d at stage 1. Then,the HESc were cultured in the condition of suspension culture for forming embryoid bodies(EBs)(stage 2). The nesting positive cells were selected in condition of ITSF medium(stage 3) and amplified in N2 and B27 medium(stage 4). Finally,LY294002 was taken as experimental(group LY) and Exendin-4 was taken as control group(group Ex),which was utilized to induce the nesting positive cells into mature insulin-producing cells. The morphology and char-acteristics of each stage were observed under the microscope,and the specific markers were identified by immunofluorescence staining. Results:The positive rates of C-peptide staining(85.7±2.1) % vs. (74.5±2.7)%,P=0.005;somatostatin staining(75.4±3.7)% vs. (31.3±4.7)%,P=0.000;glucagon staining(38.1±3.4) % vs. (27.2±2.4)%,P=0.018;insulin/c-peptide(87.5±2.4)% vs. (76.7±3.1)%,P=0.013 and insulin/somatostatin co-staining(21.5±2.2)% vs. (3.5±0.9)%,P=0.000 in group Ex were significantly higher than those of group LY. Conclusion:LY294002 could induce HESc to differentiate into more mature insulin-produc-ing cells in serum-free culture medium.

    • Study of human ZnT-8 as novel immunomodulator for type 1 diabetes mellitus

      2015, 40(7):955-959.

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      Abstract:Objective:To lay a foundation for screening novel immunomodulator for type 1 diabetes mellitus by generating human Zinc transporter 8(of ZnT-8,a novel type 1 diabetes autoantigen) recombinant protein using a prokaryotic expression system. Methods:The COOH-terminal cDNA of the human ZnT-8 gene was subcloned into the pET-32a vector and transformed into competent Es-cherichia coli(E.coli) BL21 cells. After transformation E.coli was induced using isopropyl β-D- 1-thiogalactopyranoside;human re-combinant of ZnT-8 protein was extracted,purified by Nickel sepharose affinity chromatography,and was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot. Forty female non obese diabetic(NOD) mice of four weeks old were di-vided into 2 groups in random. In ZnT-8 recombinant protein group,mice were given recombinant protein of ZnT-8;in control group,mice were given saline. The body mass,blood glucose levels and serum C-peptide levels were recorded every week. Results:The cD-NA of the carboxyl terminal of ZnT-8(306 bp) was successfully amplified by PCR. The sequence matched completely with the se-quence of ZnT-8-COOH in GeneBank. The recombinant ZnT-8-COOH was successfully expressed in a soluble form in E.coli BL21 and purified. Compared with those of control group,the body mass in ZnT-8 recombinant protein group was higher at 28 weeks old(P<0.05);the glucose levels in ZnT-8 recombinant protein group were lower at 28 weeks old(P<0.05);the serum C-peptide levels in ZnT-8-COOH group were higher at 28 weeks old(P<0.05). Conclusion:Human recombinant of ZnT-8-COOH protein is successfully prepared. The recombinant protein can be used as immunomodulator in type 1 diabetes mellitus.

    • Function of oxidative stress in apoptosis of osteoblast induced by high glucose

      2015, 40(7):960-964.

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      Abstract:Objective:To investigate the function of oxidative stress in apoptosis and proliferation of MC3T3-E1 cells under high glucose. Methods:MC3T3-E1 cells cultured in vitro were divided into normal control group,N-acetyl-L-cysteine(NAC) group,11.0 mmol/L high-glucose group,11.0 mmol/L high-glucose+NAC group,22.0 mmol/L high-glucose group and 22.0 mmol/L high-glucose+NAC group. Reactive oxygen species(ROS) production was measured with DCFH-DA fluorescent probe. Cell proliferation was mea-sured by MTT analysis. Cells in different groups were stained with Annexin V-FITC/PI,then the apoptosis rates were detected by flow cytometry. Morphology of cell nucleus was observed with Honchest33258. Results:①Cell apoptosis of 11.0 mmol/L high-glucose in-creased dramatically compared with that of normal control group(P=0.004). Cell apoptosis in 22.0 mmol/L high-glucose group in-creased significantly compared with that of normal control group and 11.0 mmol/L high-glucose group(P=0.000;P=0.000). ②Prolif-eration in 11.0 mmol/L high-glucose slightly decreased compared with that of normal control group(P=0.305). Compared with that of normal control and 11.0 mmol/L high-glucose group,proliferation in 22.0 mmol/L high-glucose group decreased significantly(P=0.001;P=0.009). ③ROS production in osteoblasts remarkablely increased under high glucose(P=0.000;P=0.000),but not in a dose-dependent manner. NAC,as an antioxidant,could reduce ROS production obviously and ameliorate cell apoptosis and proliferation abnormality caused by high glucose. Conclusion:High glucose can increase ROS production in osteoblasts and subsequently lead to the increase of apoptosis and decrease of proliferation.

    • Effect of JAZF1 over-expression on gluconeogenesis and insulin signal pathway

      2015, 40(7):965-969.

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      Abstract:Objective:To establish juxtaposed with another zinc finger gene 1(JAZF1)-transgenic mice model on the basic of cell re-search in vitro and to explore the effect of JAZF1 over-expression on gluconeogenesis and insulin signal pathway. Methods:The pre-pared JAZF1 gene fragment was microinjected into one-cell embryos of mice,then the JAZF1-transgenic mice were generated and i-dentified by standard procedures. Eight-week-old Tg-JAZF1(Tg) mice and wild type(WT) mice were randomly divided into 4 groups:standard diet(SD)-WT group(n=6),SD-Tg group(n=6),high fat diet(HFD)-WT group(n=6) and HFD-Tg group(n=6). Phospho-enolpyruvate carboxykinase and glucose-6-phosphatase in liver were detected by PCR and Western blot after 12 weeks. The phos-phorylation of insulin signal protein was measured by Western blot. Results:JAZF1 mRNA and protein expressions in liver,muscle and adipose tissue were elevated significantly in SD-Tg mice than in SD-WT mice(P<0.05).The expressions of gluconeogenesis gene in Tg mice were dramatically decreased compared with those of WT mice under the condition of SD or HFD(P<0.05). The phospho-rylation of insulin signal protein in liver,muscle and adipose tissue were increased in Tg mice than in WT mice(P<0.05). Conclusion:Transgenic mice model has been generated successfully. JAZF1 overexpression inhibit the expression of gluconeogenesis gene and also improve the insulin sensitivity of liver,muscle and adipose tis-sue.

    • >临床荟萃
    • Change of serum CA19-9,CA125 levels and its related factorsin patients with type 2 diabetes mellitus

      2015, 40(7):970-974.

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      Abstract:Objective:To investigate the association between serum CA19-9,CA125 levels and its related factors in T2DM patients. Methods:Totally 117 T2DM patients and 132 healthy subjects who had medical checkups were recruited to compare metabolic in-dices including blood glucose,lipids and protein as well as serum CA19-9 and CA125 levels. The change in CA19-9 and CA125 lev-els before and after treatment was observed. Results:(1)Statistically significant differences were found between normal controls and T2DM patients in serum CA19-9,CA125 levels and metabolic components including glucose,lipids and protein(all P<0.05). (2)There were statistical differences in serum glucose,CA19-9 and CA125 levels in T2DM patients with a HbA1c>7.5% when compared with those with a HbA1c≤7.5%(all P<0.05). (3)When compared with patients with no complication and those with chronic compli-cations,T2DM patients with acute complications had statistically different serum levels of glucose,CA19-9 and CA125(all P<0.05). (4)Carbohydrate antigens of T2DM patients with abnormal CA19-9 or CA125 were significantly lower after treatment than before treatment(all P<0.05). (5)Correlation analysis revealed that glucose,HbA1c and total cholesterol were positively correlated with CA19-9,CA125 levels in T2DM patients. Serum albumin was negative correlated with CA19-9 and CA125 levels in T2DM patients. Conclusion:T2DM patients exists not only glucose and lipid metabolism disorders,but also disorders of protein metabolism. More evi-dent increase in CA19-9 and CA125 levels will arise if the T2DM patient has poorer glycemic control. With the improvement of glycemic control,CA19-9 and CA125 levels will decrease. The change in serum and CA125 levels in T2DM patients is likely to be associated with disorders of glucose,lipid and pro-tein metabolism.

    • Lipid accumulation product as an effective index for accessing insulin resistance in patients with adult growth hormone deficiency

      2015, 40(7):975-980.

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      Abstract:Objective:To investigate the correlation of lipid accumulation product(LAP) with anthropometrics,glucolipid metabolic markers and insulin resistance(IR) in patients with adult growth hormone deficiency(AGHD). Methods:Totally 42 patients with AGHD and 42 control subjects matched with the age and gender were enrolled. The general anthropometries and blood biochemical indexes were measured. Body mass index(BMI),waist-hip ratio(WHR),LAP and HOMA-IR were calculated. Results:Compared with those in control group,the waist circumference(WC),WHR,fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),triglyceride(TG) and LAP were increased in AGHD group,while high density lipoprotein-cholesterol(HDL-C) level was lower in AGHD group(P<0.05). Weight,BMI,WC,WHR,SBP,DBP,FINS,HOMA-IR and TG increased as LAP increased(P<0.05). Pearson analysis revealed that LAP was positively related with age,BMI,WC,HC,WHR,systemic blood pressure(SBP),dias-tolic blood pressure(DBP),FINS,HOMA-IR,TG and low density lipoprotein cholesterol(LDL-C)(P<0.05). After age was adjusted,the positive correlations were still existed(except DBP). In ad-dition,HOMA-IR was positively correlated with BMI,WC and TG(P<0.05). LAP was higher in AGHD patients with IR. ROC analysis showed that LAP was a significant discriminator for IR in AGHD patients,and the optimal cutoff point of LAP to pre-dict IR was 31.32(90.9% sensitivity,61.30% specificity). Fur-ther more,multivariable linear regression models revealed that BMI,SBP,HOMA-IR were independently related with the LAP(β=0.414,0.249,0.329,resp,P<0.05). Conclusion:The LAP is sig-nificantly higher in AGHD patients than control subjects. LAP is associated with IR and had a strong and reliable diagnostic accuracy for IR in AGHD patients.

    • Relation between youth serum lipoprotein-associated phospholipase A2 levels and insulin resistance and its clinical significance

      2015, 40(7):981-985.

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      Abstract:Objective:To investigate the relation between youth serum lipoprotein-associated phospholipase A2 levels and insulin re-sistance and its clinical significance. Methods:One hundred and sixty subjects were enrolled into this study,including 87 women and 73 men with an average age of (33.4±1.2) years. Anthropometric indicators such as height,weight and biochemical markers such as serum lipid profile,plasma glucose,and serum insulin level were examined. ELISA was used to detect serum lipoprotein-associat-ed phospholipase A2(Lp-PLA2) levels. According to body mass index(BMI) and the results of oral glucose tolerance test(OGTT),we recruited 65 cases of normal weight-normal glucose tolerance(NW-NGT),45 cases of overweight-obesity-normal glucose tolerance (OB-NGT) and overweight-obesity-type 2 diabetes(OB-T2DM) in total. Results:The OB-NGT group and OB-T2DM group had higher Lp-PLA2,homeostasis model assessment-insulin resistance index(HOMA-IR),BMI,low density lipoprotein-cholesterol(LDL-C),fasting insulin(FINS) and high sensitivity C-reactive protein(hs-CRP) levels compared with those of NW-NGT group(all P<0.05). As was shown by Pearson correlation analysis,HOMA-IR had a significantly positive correlation with serum Lp-PLA2 level,BMI,hs-CRP and waistline. Multiple linear stepwise regres-sion analysis statistics indicated that HOMA-IR was the inde-pendent factor of serum Lp-PLA2 level(t=4.201,P=0.000). In addition,we used Youden’s index(YI) to determine the best threshold. YI got its maximum value,when Lp-PLA2 level was 21.0 ng/ml,which therefore was thought to be the best cut-off point for diagnosis of insulin resistance. Conclusion:Increased youth serum Lp-PLA2 level is closely related to insulin resistance,At the same time serum Lp-PLA2 is an independent risk factor of insulin resis-tance,which provides a certain clinical value in predicting the occurrence of insulin resistance.

    • Medical conservative treatment for glucagonoma:report of one case

      2015, 40(7):986-988.

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      Abstract:

    • Analysis on four cases of oral contraceptive pills induced pseudo-Cushing’s syndrome

      2015, 40(7):989-992.

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      Abstract:Objective:To study clinical features of four cases of oral contraceptive pills(OCPs) induced pseudo-Cushing’s syndrome and to review the literature related to cortisol assay affected by OCPs. Methods:The clinical features of the four childbearing age fe-male patients,who have taken OCPs due to oligomenorrhea,were analyzed retrospectively. The cross-reactivity between OCPs and serum total cortisol were analyzed retrospectively. Results:Elevated serum total cortisol was found in four patients while taking OCPs. Serum total cortisol of three patients returned to be normal after OCPs discontinuance. Based on the results of equal dilution,the cross-reactivity of serum total cortisol in OCPs was insignificant. OCPs may affect serum total cortisol in two ways as reported in the litera-ture:estrogen increases cortisol-binding globulin,causing elevated serum total cortisol;OCPs may directly stimulate the hypothalamic-pituitary-adrenal axis to generate cortisol. Conclusion:OCPs may result in pseudo-Cushing’s syndrome by a variety of mechanisms. Clinicians should pay attention to this issue to avoid misdiagnosis and mistreatment.

    • >糖影不离
    • Effect of exogenous hydrogen sulfide on myocardial fibrosis and MMP-13,MMP-14 and TIMP-1 expression in myocardial tissues of diabetic rats

      2015, 40(7):993-996.

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      Abstract:Objective:To investigate the effects of exogenous hydrogen sulfide on the expression of type Ⅲ collagen,tissue inhibitor of metallo proteinase-1(TIMP-1),matrix metalloproteinase-13(MMP-13) and MMP-14 protein and myocardial fibrosis. Methods:To-tally 52 male SD rats were randomly divided into four groups(n=13):control group,diabetes rats group(STZ group),diabetes rats treated with H2S group(STZ+H2S group),normal rats treated with H2S group(H2S group). Diabetic rats were induced by intraperi-toneal injection of streptozotocin(STZ,40 mg/kg). Rats in control group were only given intraperitoneal injection with equal amount of normal saline(NS). STZ group and H2S group were injected with NaHS(the provider of H2S,100 μmol/kg) solution. The patho-logical morphological changes in myocardial fiber were analyzed by HE staining and VG staining;the expressions of type Ⅲ collagen,TIMP-1,MMP-13 and MMP-14 were analyzed by Western blot. Results:The number of rats in each group after successful modeling was 12,9,9 and 10,respectively. Compared with those of control group,collagen deposition and myocardial fibrosis increased obvious-ly,the expressions of type Ⅲ collagen,MMP-13,MMP-14 and TIMP-1 were significantly increased(P<0.01) in STZ group,which were dramatically reversed by H2S treatment(P<0.01). Conclusion:H2S could reduce myocardial fibrosis in diabetic rats,which may be related to the inhibition of MMP-13,MMP-14 and TIMP-1 expression.

    • Tryptase and the mechanism of type 2 diabetic cardiomyopathy

      2015, 40(7):997-1000.

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      Abstract:Objective:To study the effect of tryptase on Wistar rats in type 2 diabetic cardiomyopathy model and to provide theoretical basis for the further treatment of diabetic cardiomyopathy. Methods:Totally 45 male Wistar rats were randomly separated into 3 groups:normal control(NC) group,type 2 diabetic cardiomyopathy(DCM) group and trypsin inhibitor groups(intervention group). The rats of DCM and intervention group received intrapperitioneal injection of streptozotocin after high fat and high glucose breeding to form an experimental model of diabetes cardiomyopathy. The rats of intervention group received 0.025% ketotifen solution 1 mg/kg twice a day by hypodermic injection. Rats in NC and DCM groups were given injection of physiological saline. After the experiment,all the rats were sacrificed. Body,all heart,left ventricular were weighted to calculate all heart and left ventricle weight index. Myocardial tissue was observed under the light microscopy;serum tumor necrosis factor-α(TNF-α) was tested by ELISA;trypsin protein ex-pression in rats of left ventricular myocardial tissue was examined by Western blot. Results:All heart and left ventricle weight index of DCM group was significantly higher than that of NC group(P<0.05). All heart and left ventricle weight index of intervention group was lower than that of DCM group(P<0.05). Routine HE staining results showed that,compared with those of NC group,myocardial tissue pathological changes were more visible in DCM group:disordered arrangement of cardiac muscle fiber fracture,myocyte hypertrophy,apoptosis,uncleared cell nucleus edge. Myocardial cell volume was narrowed in DCM group than in intervention group;in intervention group,myocardial cell arranged regularly with rare fracture and similar nucleus size. Serum TNF-α was significantly higher in DCM group than in NC group(P<0.05). TNF-α was lower in in-tervention group than in DCM group. Tryptase relative grey value was higher in DCM group than in NC group(P<0.05). Tryptase relative grey value was lower in intervention group than in DCM group(P<0.05). Conclusion:The type 2 diabetic rats myocardial tissue has high expression of tryptase. After injection of trypsin inhibitor intervention,myocardial pathology and the expression of tryptase in diabetic cardiomyopathy rat model decreased. The increase of tryptase expression maybe participate in the occurrence of diabetic cardiomyopathy.

    • Significance of serum 25-hydroxyvitam in D3 level in familial type 2 diabetes mellitus with diabetic retinopathy in Kunming

      2015, 40(7):1006-1010.

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      Abstract:Objective:To investigate the significance of serum 25-hydroxyvitamin D3 level in familial type 2 diabetes mellitus (T2DM)with diabetic retinopathy(DR) in Kunming. Methods:Totally 183 T2DM patients with family history of T2DM and DR(DR1 group),79 patients with family history of T2DM and without DR(DR0 group) and 156 healthy individuals(NC group)were enrolled. Clinical data of all subjects including height,weight,blood pressure and other clinical indexes were recorded. Biochemical indexes including blood glucose,blood lipids,HbA1c,insulin-C peptide were examined in three groups. The levels of 25(OH)D3 were mea-sured by ELISA;3 groups were divided based on levels of 25(OH)D3 according to the common criterions and referenced criterions. Percentages of patients in each level of 25(OH)D3 and the difference between the two criterions were compared. Correlation analysis and logistic regression analysis of 25(OH)D3 in DR1 group,as well as multiple stepwise regression analysis of risk factors for DR were conducted. Results:The prevalence of vitamin D insufficiency/deficiency was as high as up to 90% in three groups;the prevalence was higher in DR1 group than in NC group. There was no statistically significance in ratio of the different 25(OH)D3 levels of the com-mon criterions and reference criterions in three groups(P >0.05). Pearson correlation analysis of 25(OH)D3 in DR1 group showed that duration of T2DM,total cholesterol,high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol was positively correlated(r=0.162,0.164,0.189,0.175;P<0.01),and logistic regression analysis showed that the only variable in the model was HDL-C(r=0.887,P=0.010). Conclusion:Vitamin D level is generally low in the south population of China. There is no difference between common criterions and reference criterions of different 25(OH)D3 levels in three groups.

    • >谈糖话药
    • Research progress of bromocriptine in type 2 diabetes

      2015, 40(7):1011-1015.

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      Abstract:Bromocriptine,a type of novel antidiabetic agents acting on central nervous system,has been proved to be effective and safe according to current clinical trials. This article reviewed pharmacological mechanisms of bromocriptine and its current clinical trails.

    • Effects of Dai Zong Fang on 3T3-L1 adipocyte differentiation and related gene expression

      2015, 40(7):1016-1020.

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      Abstract:Objectives:To study the effect of Dai Zong Fang(DZF) on 3T3-L1 preadipocytes differentiation and changes in expression of differentiation associated genes. Methods:3T3-L1 preadipocytes cells were induced into mature adipocytes by Cocktail(1-methyl-3-isobutylxanthine,dexamethasone and insulin),treated by different concentrations of DZF from 2 d to 8 d of differentiation. The lipid accumulation of adipocyte was observed by BODIPY493/503 and DAPI double fluorescent staining. The intracellular triglyceride(TG) was detected by glycerol phosphate oxidase and peroxidase. RT-PCR was used to detect mRNA expression of CCAAT enhancer bind-ing protein-α(C/EBP-α),peroxisome proliferators-activated receptors-γ(PPAR-γ),acetyl-CoA carboxylase(ACC),fatty acid syn-thetase(FAS). Western blot was used to detect protein expression of PPAR-γ and C/EBP-α. Results:DZF could inhibit adipocyte differentiation and reduce intracellular TG content in a dose-dependent manner. ACC mRNA expression was significantly down-regulated in large-dose DZF group than in control group(P<0.05). FAS mRNA expression was significantly down-regulated in small,medium,large-dose DZF groups than in control group(P<0.01). C/EBPα and PPAR-γ mRNA expression was significantly down-regulated in medium,large-dose DZF groups than in control group(P<0.01). The result of Western blot was consistent with that of mRNA results. Conclusion:DZF could significantly inhibit the differentiation of adipocyte,the mechanisms might be related to the down-regulation of C/EBPα,PPAR-γ,ACC,FAS gene expression.

    • Research progress of diabetic nephropathy and SGLT2 inhibitors

      2015, 40(7):1021-1024.

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      Abstract:In recent years,sodium-glucose co-transport 2(SGLT2) inhibitors become a hot topic in diabetes mellitus research be-cause of their unique mechanism. SGLT2 inhibitors not only function on controlling plasma glucose level and HbA1c,but also have some extra therapeutic benefits,for example,reducing the body weight,lowering blood pressure and serum lipids,improving insulin resistance,etc.,indicating a potential protective action on diabetic nephropathy. Compared with the blockade of the RAAS,a classic therapy for diabetic nephropathy in recent years,SGLT2 inhibitors may ameliorate renal end points,leading to a sustainable renal function and a decrease in albuminuria. Thus,SGLT2 inhibitors may be used to improve the long-term outcomes of diabetic nephro-pathy,and grows to be a therapy for diabetic nephropathy.

    • Effect of palmitic acid on the expression of PI3K/Akt in human umbilical vein endothelial cells and the intervention of liuweidihuang pill

      2015, 40(7):1025-1028.

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      Abstract:Objective:To observe the effect of palmitic acid(PA) on the expression of PI3K/Akt mRNA and protein in human umbili-cal vein endothelial cells(HUVEC) and the intervention of the serum containing liuweidihuang pill(LWDHP). Methods:Firstly the serum containing LWDHP was prepared,and then the human umbilical vein endothelial cells were divided into normal group,model group,LWDHP group with serum containing concentration of 5% and metformin(MET) group. The mRNA and protein expression lev-els of PI3K/Akt were determined by RT-PCR and Western blot,respectively. Results:RT-PCR showed that mRNA expression of PI3K/Akt was significantly lower in model group than in normal group(PPI3K=0.000,PAkt=0.000),while mRNA expression of PI3K/Akt was significantly higher in 5% LWDHP group(PPI3K=0.012,PAkt=0.000) and in MET group(PPI3K=0.000,PAkt=0.000) than in model group. There were statistically significant differences in mRNA expression of PI3K/Akt between MET group and 5% LWDHP group(PPI3K=0.000,PAkt=0.000). Western blot showed that protein expression of PI3K/P-Akt was also significantly lower in model group than in normal group(PPI3K=0.000,PP-Akt=0.000),while protein expression of PI3K/P-Akt was also significantly higher in 5% LWDHP group(PPI3K=0.000,PP-Akt=0.000) and in MET group(PPI3K=0.000,PP-Akt=0.000) than in model group. There were statistically significant differences in protein expression of PI3K/Akt between MET group and 5% LWDHP group(PPI3K=0.003,PP-Akt=0.001). Conclusion:The serum containing LWDHP could promote the expression of PI3K/Akt mRNA and protein in HUVEC damaged by PA.

    • New application of salicylates in improving glucose metabolism in patients with type 2 diabetes mellitus

      2015, 40(7):1029-1031.

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      Abstract:Chronic low-grade inflammation participates in the pathogenesis of insulin resistance and type 2 diabetes mellitus. Clinical data show that salicylates can improve glucose metabolism in patients with type 2 diabetes. However,its hypoglycemic mechanism is unclear. Some studies have indicated that in addition to inhibiting inflammation,salicylates can reduce glycemia through other ways such as alleviating oxidative stress,activating AMP-activated protein kinase and decreasing free fatty acid level. This article reviewed the literature in recent years about the effect of salicylates on glucose metabolism,which will provide new ideas for the further studies of the application of salicylates in type 2 diabetes mellitus.

    • Effects of celecoxib on gastric emptying in diabetic gastroparesis rat

      2015, 40(7):1032-1036.

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      Abstract:Objective:To investigate the effects of celecoxib on gastric emptying in diabetic gastroparesis rat. Methods:Male SD rats were divided into normal control group,experimental group. Diabetes was induced by intraperitoneal injection of streptozotocin(STZ,50 mg/kg) and diabetic gastroparesis(DGP) was induced by feeding with a high-carbohydrate/high-fat diet. The normal control group(NC group,n=7) was injected with equivalent phosphate buffer solution and fed with standard diet. After 8 weeks,the diabetic rats were randomly divided into two groups ,namely diabetic gastroparesis group(DGP group,n=7) and celecoxib-treated group(CE group,n=7). The diabetic rats were orally administered with celecoxib [40 mg/(kg·d)] for 3 weeks. Gastric emptying was detected through semisolid method. The mRNA expression of COX-2 was measured by quantitative reverse transcription-PCR. COX-2 protein level was assessed by Western blot. Moreover,prostaglandin E2(PGE2) was quantified by ELISA. The ultrastructural of gastric muscle was evaluated by transmission electron microscopy. Results:Celecoxib significantly improved the gastric emptying of DGP rat(F=64.123,P=0.000). Meanwhile,celecoxib decreased the expression of COX-2 mRNA(F=9.928,P=0.005) and COX-2 protein(F=28.543,P=0.001) and PGE2(F=55.378,P=0.000) of gastric antral smooth muscle. There were swollen mitochondria and vacuolation in the gastric muscle of DGP rats. Only several myelin figures emerged in celecoxib-treated group. Conclusion:Celecoxib may ame-liorate gastric emptying of DGP rat through inhibition of the COX-2/PGE2 pathway.

    • Effects of liraglutide on expression of angiotension-Ⅱ type 1 and type 2 receptors in renal tissues of rats with diabetic nephropathy

      2015, 40(7):1037-1041.

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      Abstract:Objective:To explore the effects of liraglutide on renal angiotension Ⅱ type 1 receptor(AT-1R) and angiotensionII type 2 receptor(AT-2R) of rats with type 2 diabetes. Methods:Forty adult male sprague-dawley rats were randomly separated into three groups:normal control group(NC),diabetic model group(DM) and liraglutide group(LR). The rats of DM and LR group received in-traperitioneal injection of low dose of streptozotocin(STZ) after high fat and high glucose breeding to form an experimental model of type 2 diabetes. The rats of NC and LR group received liraglutide 100 ug/kg twice a day by hypodermic injection and the rats of DM group received injection of physiological saline. Twelve weeks after the build of type 2 diabetes model,the following indicators were assayed:(1)24 h urinary albumin excretion rate(UAER),serum creatinine(Scr) and blood urea nitrogen(BUN);(2)body weight(BW),kidney weight(KW),KW/BW,mean glomerular volume(MGV) and fractional mesangial area(FMA);(3)the changes of patho-logic feature of the kidney by periodic acid-silver methe-namine staining(PASM) and electron microscope;(4)the change of expres-sion of AT-1R and AT-2R in kidney of rats by immunohistchemistry and RT-PCR. Results:(1)Liraglutide can markedly suppress the augmentation of KW/BW,MGV,FMA,Scr,BUN and UAER as well as attenuate the renal pathologic lesions such as podocyte foot process fuse and glomerular basement membrane(GBM) thickening. (2)Liraglutide can up-regulate the expression of AT-2R in the kidney of diabetic rats meanwhile has no evident effect on the expression of AT-1R. Conclusion:Mechanism of reno-protection of li-raglutide may at least partly correlate with increased expression of AT-2R and change in balance of AT-1R/AT-2R of renal tis-sue.

    • >论糖天下
    • Epidemiology and research advances in diabetes mellitus in China

      2015, 40(7):1042-1044.

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      Abstract:Diabetes mellitus,as a common chronic disease,has become a public health problem worldwide. The prevalence of diabetes in China has become the highest all over the world. Such rapidly increasing prevalence year after year was caused by genetic factors,improvement of socioeconomic status,aging of population,and most importantly,the change of life style. In addition,the revision of diagnosis criteria of diabetes also influences its prevalence. In China,the diagnosis of diabetes has been made according to 1990 WHO diagnostic criteria of diabetes for a long time. Whether glycosylated hemoglobin(HbAlc) should be included in the new criteria is still under discussion. Diabetes as well as its complications greatly compromises the patients’ quality and expectation of life,and brings heavy burden to both the patients and social health care system. Therefore the early diagnosis and treatment of di-abetes are crucial. However,the low awareness rate,treatment rate and target rate,along with the high prevalence of diabetes reflect that the management of diabetes is in urgent need of improvement. The cooperation of patients,government,public health and medical institution is warrant to better solve this public health problem with its early diagnosis,treatment and control.

    • Changes in incidence of metabolic syndrome and its components in a community in Chongqing:a ten-year follow-up study

      2015, 40(7):1045-1049.

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      Abstract:Objective:To investigate the changes in the incidence of metabolic syndrome and its components in a community in Chongqing during a period of ten years. Methods:Physical examinations including questionnaires,anthropometric measurements,fast-ing and postprandial blood glucose levels and blood lipid level testing were carried out in the community population in the years 2003,2008,and 2013 respectively. In the study,the criterion established by the Chinese Medical Association Diabetes Society(CDS) in 2013 was used to diagnose metabolic syndrome. Results:The number of participants in 2003,2008 and 2013 were 3 140,3 867 and 5 429 and the standardized prevalences of the metabolic syndrome were 21.0%,21.3% and 25.4% respectively,which increased sig-nificantly(?字2=30.85,P<0.01). Incidence of both hypertension and hyperglycemia increased significantly during the ten years. Conclu-sion:The prevalence of metabolic syndrome significantly increased in the community in the recent ten years due to an increased inci-dence in hypertension and hyperglycemia.

    • >他山之石
    • The thermogenic circuit:regulators of thermogenic competency and differentiation

      2015, 40(7):1050-1054.

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      Abstract:在哺乳动物中,存在着一种增加热量产生和能量消耗的产热机制。最近研究揭示了控制这个产热环路的细胞和生理学机制。该产热机制可激活脂肪细胞,即棕色及与之密切相关的浅棕色脂肪细胞,由那些具有产热功能但起源于不同细胞组织的祖细胞谱系分化而成。热能产生的分化与普通脂肪细胞生成有相同之处,值得强调的是一些共同的转录因子在操纵祖细胞不同结局的过程中扮演了重要角色。然而,热能产生的分化并非一定与普通的程序性的脂肪细胞生成相关,令人兴奋的是,具有特定来源的细胞拥有热能产生的代偿能力,即能够使他们分化成为可产热活性的成熟脂肪细胞。对热能产生的程序性分化和其中激活因素的理解有助于开发直接或间接检测热能产生活性的指标和试剂盒。在合适的细胞模型中联合运用这些指标,可以开发出新的通过增强产热环路来对抗肥胖及其相关代谢性疾病的治疗方法。

    • How to do a 3-minute diabetic foot exam

      2015, 40(7):1055-1058.

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      Abstract:

    • >糖影不离
    • Correlation between serum 25-hydroxyvitamin D level and carotid artery intima-media thickness in type 2 diabetic patients

      2015, 40(7):10001-1005.

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      Abstract:Objective:To evaluate the correlation between serum 25-hydroxy vitamin D(25(OH)D) level and carotid artery intimal-medial thickness(IMT)in type 2 diabetic(T2DM) patients. Methods:Totally 132 T2DM patients were divided into four quartile groups(Q1-Q4) according to the level of serum 25(OH)D and were divided into normal group and atherosclerotic group according to their IMT. Their blood pressure,body weight,body height,and biochemical indexes were measured. Their serum 25(OH) D level was mea-sured by ECL. Their carotid IMT,peak systolic velocity,(PSV),end diastolic velocity(EDV) were measured by ultrasongraphy. Results:Carotid IMT in Q1 group was significantly higher than that in Q3 group(P=0.027). Carotid IMT in Q1 and Q2 groups were signifi-cantly higher than that in Q4 group(P=0.000;P=0.002). Prevalence of carotid atherosclerotic plaque in Q1 group was significantly higher than that in Q2,Q3 and Q4 groups(P=0.004;P=0.002;P=0.000). The carotid PSV was significantly lower in Q1 group than that in Q3 group(P=0.031). Similarly,the carotid EDV was significantly lower in Q1 group than that in Q2,Q3 and Q4 groups(P=0.003;P=0.002;P=0.038).The serum 25(OH)D concentration was significantly lower in atherosclerotic group than that in normal group(P=0.000). Pearson correlation analysis showed that carotid IMT was negatively related with the 25(OH)D(r=-0.348,P=0.000). Multivari-ate regression analysis revealed that 25(OH)D concentration was an independent predictor of carotid IMT in this cohort(B=-0.012,P=0.000). Conclusion:Serum 25(OH)D concentration is nega-tively correlated with carotid IMT and low 25(OH)D concentra-tion may be a risk factor for carotid atherosclerosis in T2DM pa-tients.

Competent unitl:Chongqing Committee of Education

Organizer:Chongqing Medical University

Editorial Office:Editorial Department of Journal of Chongqing Medical University

Editor in chief:Huang Ailong

Editorial Director:Ran Minghui

International standard number:ISSN

Unified domestic issue:CN

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