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Effects of incretin class of antidiabetic drugs on lipid metabolism in patients with type 2 diabetes and its mechanism

Chinese Journal of Endocrinology and Metabolism.2017;33(5):435-437. doi:10.3760/cma.j.issn.1000-6699.2017.05.016

Chronic hyperglycemia is often accompanied by abnormal lipid metabolism, hypertension, low-grade systemic inflammation and oxidative stress.These factors increase the risk of cardiovascular disease(CVD)in type 2 diabetes mellitus(T2DM)patients.Comprehensive treatment of T2DM should emphasize the improvement of abnormal lipid metabolism, prevention of weight gain and reduction of the CVD risk in addition to proper glycemic control.Incretin, as a new hypoglycemic drug, has more advantages in improving glucose and lipid metabolism, finally to reduce cardiovascular risk.Through possible mechanisms including direct influence on liver lipid metabolism, change of fat mobilization and delay of gastric emptying, incretin shows positive influence on the lipid metabolic markers such as low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, and total cholesterol, while it improves glucose control.Thus, incretin plays an important role in the comprehensive management of type 2 diabetes mellitus.

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Thymic carcinoid associated to Multiple Endocrine Neoplasia type 1

Weixi WANG ; Lei YE ; Guang NING

Chinese Journal of Endocrinology and Metabolism.2017;33(5):432-434. doi:10.3760/cma.j.issn.1000-6699.2017.05.015

Thymic carcinoid is an uncommon component of Multiple Endocrine Neoplasia Type 1 (MEN1).The low penetrance and the high mortality made TH-NET one of the most fatal tumor components of MEN1.Here we are discussing the pathology and pathogenesis, as well as epidemiology, screening strategy, diagnosis, therapies, and analysis of prognostic factors of thymic carcinoid associated to MEN1.

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Clinical features and sex hormone parameters analysis in 227 male patients with 47,XXY

Zhouhui PAN ; Dongdong FU ; Jiaheng LI ; Xiaoqin DING ; Xianfeng YANG

Chinese Journal of Endocrinology and Metabolism.2017;33(5):398-401. doi:10.3760/cma.j.issn.1000-6699.2017.05.008

Objective To explore clinical characteristics of patients with Klinefelter′s syndrome(KS; 47,XXY).Methods 227 male patients with 47,XXY treated by artificial insemination with donor(AID)were included.Age, education, height, weight, body mass index(BMI), testicular volume, FSH, LH, testosterone(T), prolactin(PRL), estradiol(E2)were analyzed retrospectively.Results Of these patients, their height were(176.4±5.5)cm, weight(74.5±12.7)kg, BMI(23.89±3.66)kg/m2[77 of overweight(33.92%)and 34 of obesity(14.98%)], FSH(38.35±14.33)IU/L, LH(19.40±9.00)IU/L, T(132.00±194.50)ng/dl, E2(23.90±15.00)ng/L, PRL(10.50±8.20)μg/L, E2/T 0.21±0.80.Testicular volume had the positive association with the level of T(r=0.197, P=0.003).BMI had the negative association with the serum concentration of T(r=-0.284, P=0.000), while positive association with the E2(r=0.174, P=0.009)and ratio of E2/T(r=0.323, P=0.000).Age had no association with T, E2, and E2/T(P>0.05), but had negative association with the serum concentration of LH(r=-0.154, P=0.02)nd FSH(r=-0.196,P=0.03).The higher education group were older(P<0.01), while the level of T were lower(P<0.01).Conclusion In patients with Klinefelter′s syndrome(KS; 47,XXY), level of T may associate with testicular volume.T, E2, and the ratio of E2/T seem to associate with their height, BMI, and education level.

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Risk factors for radioiodine-refractoriness and survival analysis of differentiated thyroid cancer with distant metastasis

Yan XIE ; Ling JIANG ; Kehua ZHOU ; Fangxian JIA

Chinese Journal of Endocrinology and Metabolism.2017;33(5):387-391. doi:10.3760/cma.j.issn.1000-6699.2017.05.006

Objective To analyze clinical risk factors for radioiodine(RAI)-refractoriness of DTC with distant metastasis and do survival analysis.Method The clinical data of 77 differentiated thyroid cancer(DTC) patients with distant metastasis admitted to the department of radionuclide therapeutics of Qilu Hospital from Jan 2002 to Sep 2015 were collected to make the retrospective analysis by dividing into radioiodine-refractory(RAI-R) group and radioiodine-efficient(RAI-E) group.Result (1)In DTC patients treated by 131I, there are 77(7.15%) patients with distant metastasis.Among DTC with distant metastasis, 25(32.47%) patients are identified as RAI-R DTC with average age of (56.2±16.0) years old, median age of 57 years old, and male-to female ratio of 1∶2.57.(2)Univariate analysis shows that age of distant metastasis older than 45 years and pathological type of follicular thyroid cancer(FTC) are two risk factors related to RAI-refractoriness.Logistic regression analysis indicates that age of distant metastasis older than 45 years and pathological type of FTC are the independent risk factors for RAI-refractoriness of DTC with distant metastasis.(3)3-year and 5-year survival rates of the 25 RAI-R DTC patients with distant metastasis are 75% and 62%,while RAI-E DTC patients were all alive.The survival of RAI-R DTC with distant metastasis is significantly worse than RAI-E DTC with distant metastasis.Conclusions (1)In the DTC with distant metastasis, the rate of RAI-R DTC is not low, and it is 32.47%.Females of RAI-R DTC are more than males.(2)Age of distant metastasis older than 45 years and pathological type of FTC are independent risk factors for RAI-refractoriness of DTC with distant metastasis.(3)The survival rate of RAI-R DTC with distant metastasis was significantly lower than that of RAI-E DTC with distant metastasis.

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The role of soluble interleukin 2 receptor in bone metabolism of Graves′ disease in women

Yun WANG ; Yan LING ; Xin GAO

Chinese Journal of Endocrinology and Metabolism.2017;33(5):382-386. doi:10.3760/cma.j.issn.1000-6699.2017.05.005

Objective To examine the relationship between plasma soluble interleukin 2 receptor(sIL2R), bone metabolism markers, and bone mineral densities in female patients with Graves′ disease(GD), and to explore the role of sIL2R in bone metabolism of GD.Methods This study included 201 female GD patients.FT3, FT4, TSH, PTH, osteocalcin(OCN), C-terminal telopeptides of type Ⅰ collagen (CTX), procollagen type I N-terminal propeptide(PINP), and 25-(OH)-vitamin D(25OHD) were measured using electrochemical luminescence technique.sIL2R was measured using chemiluminescence method.All pations underwent examinations of bone mineral densities at lumbar spine, total hip, and femoral neck(LS-BMD, TH-BMD, and FN-BMD).The associations of sIL2R with bone metabolism markers and bone mineral densities were analyzed.Results OCN,CTX,PINP gradually decreased across the tertile groups of LS-BMD, TH-BMD, FN-BMD(all P<0.05).FT3, sIL2R gradually increased across the tertile groups of OCN, CTX, PINP(all P<0.05).Multiple linear regression analysis showed that sIL2R was independently associated with OCN and CTX(both P<0.05).Conclusion The increase of bone turnover leads to bone loss in female GD patients.The plasma level of sIL2R was positively correlated to bone turnover, which indicated that sIL2R may play an important role in bone metabolism of GD.

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Research on the correlation between uric acid levels and thyroid nodules and gender differences

Yao LIU ; Ziwei LIN ; Chunjun SHENG ; Dajin ZOU ; Zhongwei LYU ; Huixiong XU ; Yikun ZHU ; Yun HUANG ; Ni ZHONG ; Zhao JIA ; Qing WEI ; Shen QU

Chinese Journal of Endocrinology and Metabolism.2017;33(5):377-381. doi:10.3760/cma.j.issn.1000-6699.2017.05.004

Objective To explore the correlation between thyroid nodules and uric acid levels and to find their gender differences.Methods A total of 68 056 subjects in a regional medical physical examination center of Shanxi Province from January 2013 to June 2015 were enrolled in this study.All the participants′ general information and parameters were recorded.Thyroid nodules were detected by color Doppler ultrasonography.Results The total prevalence of thyroid nodule was 35.5%, 30.7% in males and 40.0% in females.The prevalence of single nodule was 50.1%, and multiple 49.9%.Compared with no nodule group, thyroid nodule group tended to be older, with higher BMI, and with a worse metabolic status(all P<0.01).The uric acid levels were lower[(352.37±78.14 vs 357.70±77.51) μmol/L, P<0.01] in thyroid nodule group in male and higher[(260.22±61.91 vs 253.91±59.18) μmol/L, P<0.01] in female.Conclusion Thyroid nodules may be associated with metabolism and inflammation.In males, hyperuricemia group had lower, while in females, hyperuricemia ones were with a higher prevalence of thyroid nodules.

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Implication of proinsulin to insulin ratio in the basic and clinical research of diabetes

Junling LIU ; Rui WEI ; Tianpei HONG

Chinese Journal of Endocrinology and Metabolism.2017;33(5):449-452. doi:10.3760/cma.j.issn.1000-6699.2017.05.019

Proinsulin is the precursor of mature insulin.Proinsulin to insulin ratio reflects the degree of pancreatic β-cell dysfunction and the progression of type 2 diabetes, and may predict the risk of diabetes development.Some variants in susceptibility genes of diabetes are associated with the elevation of proinsulin to insulin ratio.Moreover, several antidiabetic drugs are able to decrease the proinsulin to insulin ratio in patients with type 2 diabetes.Therefore, the proinsulin to insulin ratio may act as a simple and useful indicator in the etiological study, risk prediction, disease progression and therapeutical evaluation in type 2 diabetes.

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Repaglinide effected on proliferation, differentiation, and apoptosis of pre-osteoblasts MC3T3-E1 subclone 14 cell in hyperglycemia condition

Shuxin REN ; Siyu WANG ; Fuguang LI ; Yurong WANG ; Chen XU ; Huijuan ZHANG

Chinese Journal of Endocrinology and Metabolism.2017;33(5):420-424. doi:10.3760/cma.j.issn.1000-6699.2017.05.012

Objective This study examined the effects of repaglinide on the proliferation, differentiation, and apoptosis of mouse pre-osteoblasts MC3T3-E1 subclone 14 cell under high glucose condition.Methods MC3T3-E1 cells cultured in vitro for 48h were divided into the following groups: control group and repaglinide with different concentrations (0.01, 0.1, 1, and 10 μmol/L).Cell proliferation was measured by CCK-8 assay.mRNA levels of type I collagen(COL-Ⅰ), osteopontin(OPN) and alkaline phosphatase(ALP) were assayed using quantitative real-time PCR.Expression of apoptosis related proteins (Bcl-2, Bax) was measured by western blot analysis.Results (1)Compared with control group, the proliferation rate of repaglinide with different concentrations increased, while the proliferation rate of the 1 μmol/L repaglinide group significantly higher than that of the control group(P<0.05).(2) There was no significant difference on the COL-Ⅰ mRNA expression among the repaglinide groups and the control group(P>0.05).Compared with control group, the OPN and ALP mRNA expression increased significantly in the 1 μmol/L repaglinide group(P<0.05), while the OPN expression was significantly declined in the 10 μmol/L repaglinide group(P<0.05).(3)The protein expression of Bcl-2 was positively related with repaglinide concentration(P<0.05), while the protein expression of Bax went down in the 1 and 10 μmol/L repaglinide groups(P<0.05).Conclusion When exposed to high glucose concentration, repaglinide in a certain concentration range may promote the proliferation and differentiation of MC3T3-E1 subclone 14, while restrain its apoptosis.

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Gcm2 gene knock-out induces the hypoparathyroidism in adult mice

Sheng QIU ; Yu LIAN ; Qinan WU ; Bing CHEN

Chinese Journal of Endocrinology and Metabolism.2017;33(5):413-419. doi:10.3760/cma.j.issn.1000-6699.2017.05.011

Objective To investigate the role of Glial cells missing 2 (Gcm2) in pathogenesis of hypoparathyroidism by knocking out Gcm2 gene in adult mice.Methods Tamoxifen was used to induce conditional knock-out of Gcm2 gene in Gcm2E2fl/flCre-ER mice.Genotypes of knock-out mice were identified by PCR.The protein expression level of Gcm2 was measured by Western blotting.The serum calcium and phosphorus were detected by the calcium and phosphorus assay kits, and the serum parathyroid hormone (PTH) level was detected by ELISA.Parathyroid cell proliferation was tested by Ki-67 immunohistochemical assay.The mRNA expression levels of PTH and calcium sensing receptor (CaSR) were detected by Real-time PCR.Bone mineral density was detected by micro CT.Results Gcm2 gene of parathyroid was confirmed to be knocked out by PCR.Compared with wild type and solvent control groups, Gcm2 knock-out group showed markedly lower protein expression of Gcm2, notably higher serum phosphorus and lower serum calcium and PTH concentrations (all P<0.01).The proliferation of parathyroid cells in Gcm2 knock-out mice were significantly higher(both P<0.01).The mRNA levels of PTH and CaSR in parathyroid gland of the knock-out group were significantly reduced (all P<0.01).Bone mineral density was significantly higher in Gcm2 knock-out group (all P<0.01).Conclusion Knockout of Gcm2 can lead to hypoparathyroidism in adult mice, indicating that Gcm2 is probably a therapeutic target for hypoparathyroidism.

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Deposition of collagen Ⅰ in adipose tissue of obese mice was inhibited by toll like receptor 2 knockout

Haoqiang ZHANG ; Ru WANG ; Bing SONG

Chinese Journal of Endocrinology and Metabolism.2017;33(5):408-412. doi:10.3760/cma.j.issn.1000-6699.2017.05.010

Objective To explore the effect of TLR2 on collagen Ⅰ(colⅠ) in adipose tissue of high-fat-diet induced obese mice.Methods Male C57bl/6J mice and TLR2 knockout mice were divided into groups according to high fat diet or normal chow.Total collagen, TLR2, colⅠ, MMP1, MMP2, TIMP1, colⅠα1 mRNA and colⅠα2 mRNA in adipose tissue were measured at the end of the experiments.Results Total collagen, TLR2, colⅠ, MMP2, TIMP1, colⅠα1 mRNA, and colⅠα2 mRNA in adipose tissue increased while MMP1 in adipose tissue decreased in mice with high fat diet.Decreased levels of total collagen, colⅠ, MMP2, TIMP1, colⅠα1 mRNA and colⅠα2 mRNA in adipose tissue were detected in TLR2 gene knockout mice with high fat diet.However, there was an increased level of MMP1 in TLR2 gene knockout mice with high fat diet.Conclusion In high-fat-diet induced obese mice, deposition of colⅠ in adipose tissue seems to be alleviated by TLR2 gene knockout via MMP1 and TIMP1.

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