Publications by authors named "Jianling Du"

39 Publications

Hyperthyroidism Prevalence in China After Universal Salt Iodization.

Front Endocrinol (Lausanne) 2021 28;12:651534. Epub 2021 May 28.

Zhejiang Center for Disease Control and Prevention (Zhejiang CDC), Hangzhou, China.

Background: Universal salt iodization (USI) was implemented in mainland China in 1996. The prevalence of hyperthyroidism and its risk factors now require examination.

Methods: Data were acquired from a nationwide Thyroid, Iodine, and Diabetes Epidemiological survey (TIDE 2015-2017) of 78,470 subjects from 31 provinces. Iodine status, and thyroid hormones and antibodies were measured.

Results: After two decades of USI, the prevalence of overt hyperthyroidism (OH), Graves' disease (GD), severe subclinical hyperthyroidism (severe SCH), and mild subclinical hyperthyroidism (mild SCH) in mainland China was 0.78%, 0.53%, 0.22%, and 0.22%, respectively. OH and GD prevalence were higher in women than in men (OH: 1.16% . 0.64%, P<0.001; GD: 0.65% . 0.37%, P<0.001).Prevalence was significantly decreased after 60 years-of-age compared with 30-39 years-of-age (OH:0.61% . 0.81%, P<0.001; GD: 0.38% . 0.57%, P<0.001).Excessive iodine(EI) and deficient iodine(DI) were both related to increased prevalence of OH (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.68-2.59; OR1.35, 95%CI 1.07-1.72, respectively); however, only deficient iodine was associated with increased prevalence of GD (OR1.67, 95%CI 1.30-2.15). Increased thyroid peroxidase antibody and thyroglobulin antibody levels were significantly associated with prevalence of OH and GD, but not severe SCH and mild SCH. Although hyperthyroidism was more prevalent in women, the association disappeared after adjusting for other factors such as antibody levels.

Conclusion: OH and GD prevalences in mainland China are stable after two decades of USI. Iodine deficiency, elevated thyroid antibody levels, and middle age are the main risk factors for OH and GD. The severe SCH population, rather than the mild SCH population, shows similar characteristics to the OH population.
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http://dx.doi.org/10.3389/fendo.2021.651534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194401PMC
May 2021

The Correlation Between Metabolic Disorders And Tpoab/Tgab: A Cross-Sectional Population-Based Study.

Endocr Pract 2020 Aug;26(8):869-882

Department of Endocrinology and Metabolism, Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou, P.R. China.

Objective: Studies have shown that metabolic abnormalities influence the immune system. Because the prevalence of metabolic and autoimmune thyroid diseases has increased synchronously, the correlation between them was worth exploring. The study objective was to investigate the relationship between metabolic disorders and thyroid auto-antibodies in euthyroid subjects.

Methods: Data were obtained from the Thyroid Diseases and Diabetes Mellitus project survey of 55,891 subjects from 31 provinces in China. The body mass index (BMI), waist circumference (WC), blood pressure, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), thyroid-stimulating hormone (TSH), urinary iodine concentration, blood glucose, lipid profile, and uric acid levels were evaluated. Free thyroxine and free triiodothyronine levels were measured in patients with abnormal serum TSH levels.

Results: In males, the BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), and 2-hour post-glucose oral glucose tolerance test results of the TPOAb-/TgAb-positive group were significantly higher than those of the TPOAb-/TgAb-negative group. In females, the BMI, WC, SBP, DBP, total cholesterol, and low-density-lipoprotein cholesterol (LDL-C) in the TPOAb-/TgAb-positive group were significantly increased compared to the TPOAb-/TgAb-negative group. Multivariate analysis showed that in males, the odds ratio (OR) of positive TgAbs in the abdominal obesity group was 1.175 (95% confidence interval [CI], 1.016 to 1.359; P = .03), and the OR of positive TPOAbs in the hyperuricemia group was 1.195 (95% CI, 1.041 to 1.372; P = .011). In females, the OR of positive TgAbs was 1.19 (95% CI, 1.068 to 1.326; P = .002) in the high LDL-C group.

Conclusion: Obesity, high LDL-C, and hyperuricemia were positively correlated with the prevalence of positive thyroid autoantibodies in euthyroid subjects in a gender-dependent manner. This cross-sectional survey showed that metabolic disorders are associated with increased positive thyroid autoantibody levels in euthyroid subjects in a gender-dependent manner.

Abbreviations: AIT = autoimmune thyroiditis; BMI = body mass index; CI = confidence interval; DBP = diastolic blood pressure; FPG = fasting plasma glucose; FT3 = free triiodothyronine; FT4 = free thyroxine; HbA1c = glycated hemoglobin; HDL-C = high-density-lipoprotein cholesterol; LDL-C = low-density-lipoprotein cholesterol; OGTT2hPG = oral glucose tolerance test 2-hours post-glucose; OR = odds ratio; SBP = systolic blood pressure; TC = total cholesterol; TG = triglycerides; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyroid-stimulating hormone; UA = uric acid; WC = waist circumference.
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http://dx.doi.org/10.4158/EP-2020-0008DOI Listing
August 2020

Exposure to the Chinese Great Famine in Early Life and Thyroid Function and Disorders in Adulthood: A Cross-Sectional Study.

Thyroid 2021 04 23;31(4):563-571. Epub 2020 Dec 23.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, P.R. China.

Malnutrition in early life may permanently change the structure and function of the body, which lead to a number of diseases in adulthood. The effect of famine exposure during the early life on thyroid function and disorders remains unclear. This study investigated the association between exposure to the Great Chinese Famine (1959-1961) in early life and thyroid function and disorders in adulthood. Nine thousand eight hundred eighty-one subjects with appropriate birth dates derived from the Thyroid disorders, Iodine status, and Diabetes Epidemiological survey were included. Thyroid function and disorders were defined by the test results of blood sample and ultrasonography of all participants. Associations between famine exposure in early life and thyroid function and disorders in adulthood were assessed with binary logistic regression and linear regression. Participants exposed to the Great Chinese Famine during the fetal stage was associated with a higher thyrotropin (TSH) level in adulthood ( = 0.024;  = 0.038), compared with the nonexposed participants. The association was significant among rural participants ( = 0.039;  = 0.02) but not in urban participants ( = 0.005;  = 0.77). Fetal-exposed group did not show a higher risk of thyroid disorders than the age-matched balanced control group, including overt hyperthyroidism, subclinical hyperthyroidism, overt hypothyroidism, subclinical hypothyroidism, autoimmune thyroiditis, and thyroid nodules ( > 0.05). Famine exposure during the fetal stage was associated with a higher TSH level in adulthood. The fetal stage could be the critical period for programming the pituitary-thyroid axis.
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http://dx.doi.org/10.1089/thy.2020.0325DOI Listing
April 2021

The Effect of Increased Iodine Intake on Serum Thyrotropin: A Cross-Sectional, Chinese Nationwide Study.

Thyroid 2020 12 21;30(12):1810-1819. Epub 2020 Sep 21.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, P.R. China.

Subclinical hypothyroidism is diagnosed based on serum thyrotropin (TSH) reference intervals, which in turn are affected by many factors. Data were acquired from a Chinese nationally representative cross-sectional study of 78,470 participants (TIDE study). The total study population were participants from the TIDE program, and the reference population was a subset of the total population defined by the National Academy of Clinical Biochemistry (NACB) guidelines. Serum concentrations of thyroid hormones, TSH, thyroid antibodies, and urine iodine concentration (UIC) were measured. The geometric mean serum TSH (2.5th-97.5th) for the reference population (defined by the NACB) and total population was 2.28 mIU/L (0.74-7.04 mIU/L) and 2.34 mIU/L (0.61-8.33 mIU/L), respectively. In the reference population, increase in UIC was significantly associated with increase in the 50th and 97.5th centiles and decrease in the 2.5th centile of TSH. The median TSH was significantly higher in women than in men (2.41 mIU/L vs. 2.16 mIU/L, -value <0.001). Increased age was significantly associated with an increased TSH, 97.5th centile. For each 10-year increase in the population age, the TSH 97.5th centile increased by 0.534 mIU/L. The prevalence of subclinical hypothyroidism diagnosed according to the assay-recommended interval (Roche 0.27-4.2 mIU/L) and NACB standard interval in the TIDE study (0.74-7.04 mIU/L) differed significantly (Roche 13.61% vs. TIDE 3.00%,  < 0.05). However, there was no significant difference in future cardiovascular disease, reflected by the Framingham risk score, between the 0.27-4.2 and 4.2-7.04 mIU/L TSH groups. Serum TSH concentration significantly increased with increase in iodine intake. Thus, iodine intake must be considered in establishing TSH reference intervals. To avoid overdiagnosis and overtreatment of subclinical hypothyroidism, different areas should use individual serum TSH reference intervals.
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http://dx.doi.org/10.1089/thy.2019.0842DOI Listing
December 2020

An Inverse Relationship Between Iodine Intake and Thyroid Antibodies: A National Cross-Sectional Survey in Mainland China.

Thyroid 2020 11 23;30(11):1656-1665. Epub 2020 Jul 23.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, P.R. China.

Iodine intake is associated with thyroid autoimmunity. In this study, we evaluated the changes in thyroid autoimmunity after 20 years of universal salt iodization (USI) in China. A total of 78,470 subjects (18 years or older) from 31 provincial regions of mainland China participated in the study. Serum thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), TSH receptor antibody, thyrotropin (TSH), and urinary iodine concentration (UIC) were measured. Positive TPOAb and TgAb were detected in 10.19% [CI 9.80-10.59] and 9.70% [CI 9.28-10.13] of the subjects, respectively. The prevalence of positive isolated TPOAb (i-TPOAb), positive isolated TgAb (i-TgAb), and double positive TPOAb and TgAb (d-Ab) was 4.52%, 4.16%, and 5.94%, respectively. The prevalence of thyroid antibody positivity was the highest in the iodine-deficient (UIC <100 μg/L) groups. The prevalence of i-TPOAb was inversely associated with more than adequate iodine intake (MAI) and excessive iodine intake (EI); the odds ratio (OR) was 0.89 [CI 0.81-0.98] for MAI and 0.90 [CI 0.81-0.99] for EI. We observed that i-TgAb, like i-TPOAb, was a high-risk factor for subnormal TSH levels (OR = 3.64 [CI 2.62-5.05]) and elevated TSH levels (OR = 1.62 [CI 1.49-1.77]). The prevalence of thyroid antibody positivity varied among five ethnic groups. After two decades of USI, the prevalence of thyroid antibody positivity has remained low. MAI and EI had an inverse relationship with TPOAb positivity, which reveals that UIC between 100 and 299 μg/L is optimal and safe for thyroid autoimmunity. These conclusions need to be confirmed in a follow-up study because this study was a cross-sectional study.
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http://dx.doi.org/10.1089/thy.2020.0037DOI Listing
November 2020

Selenoprotein S attenuates endothelial dysfunction in a diabetic vascular chip.

Exp Gerontol 2020 08 28;137:110963. Epub 2020 Apr 28.

Department of Endocrinology, the First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China. Electronic address:

Endothelial dysfunction (ED) is a critical and initiating factor in the genesis of diabetic vascular complications whose occurrence and development is closely related to the complex intravascular microenvironment. However, currently, there is no dynamic model simulating the diabetic vascular endothelial microenvironment that can be used to investigate the mechanism underlying multifactor-induced ED. Here, we developed an integrated microfluidic chip as a new methodological platform to study vascular ED. Selenoprotein S (SELENOS) was found to be involved in the defense against oxidative stress-induced vascular endothelial injury in our previous studies. However, the regulatory signaling pathway underlying this process has not been described. With this chip, we demonstrated that multifactor-induced oxidative stress injury in human aortic endothelial cells (HAECs) has a synergistic effects and upregulates SELENOS expression. Subsequently, SELENOS was found to protect HAECs against multifactor-induced oxidative stress injury by regulating the PKCα/PI3K/Akt/eNOS pathway in the diabetic vascular endothelial microenvironment. Based on these data, our diabetic vascular chip provides a promising tool for studying vascular endothelial function, and SELENOS may be a novel target for prevention and treatment of diabetic macrovascular complications.
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http://dx.doi.org/10.1016/j.exger.2020.110963DOI Listing
August 2020

Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study.

BMJ 2020 04 28;369:m997. Epub 2020 Apr 28.

Department of Endocrinology and Metabolism, Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou, China.

Objective: To assess the prevalence of diabetes and its risk factors.

Design: Population based, cross sectional study.

Setting: 31 provinces in mainland China with nationally representative cross sectional data from 2015 to 2017.

Participants: 75 880 participants aged 18 and older-a nationally representative sample of the mainland Chinese population.

Main Outcome Measures: Prevalence of diabetes among adults living in China, and the prevalence by sex, regions, and ethnic groups, estimated by the 2018 American Diabetes Association (ADA) and the World Health Organization diagnostic criteria. Demographic characteristics, lifestyle, and history of disease were recorded by participants on a questionnaire. Anthropometric and clinical assessments were made of serum concentrations of fasting plasma glucose (one measurement), two hour plasma glucose, and glycated haemoglobin (HbA).

Results: The weighted prevalence of total diabetes (n=9772), self-reported diabetes (n=4464), newly diagnosed diabetes (n=5308), and prediabetes (n=27 230) diagnosed by the ADA criteria were 12.8% (95% confidence interval 12.0% to 13.6%), 6.0% (5.4% to 6.7%), 6.8% (6.1% to 7.4%), and 35.2% (33.5% to 37.0%), respectively, among adults living in China. The weighted prevalence of total diabetes was higher among adults aged 50 and older and among men. The prevalence of total diabetes in 31 provinces ranged from 6.2% in Guizhou to 19.9% in Inner Mongolia. Han ethnicity had the highest prevalence of diabetes (12.8%) and Hui ethnicity had the lowest (6.3%) among five investigated ethnicities. The weighted prevalence of total diabetes (n=8385) using the WHO criteria was 11.2% (95% confidence interval 10.5% to 11.9%).

Conclusion: The prevalence of diabetes has increased slightly from 2007 to 2017 among adults living in China. The findings indicate that diabetes is an important public health problem in China.
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http://dx.doi.org/10.1136/bmj.m997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186854PMC
April 2020

THE CORRELATION BETWEEN METABOLIC DISORDERS AND TPOAB/TGAB: A CROSS-SECTIONAL POPULATION-BASED STUDY.

Endocr Pract 2020 Apr 27. Epub 2020 Apr 27.

Department of Endocrinology and Metabolism, Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou, P.R. China, 550004.

Objectives: Studies have shown that metabolic abnormalities influence the immune system. Because the prevalence of metabolic and autoimmune thyroid diseases has increased synchronously, the correlation between them was worth exploring. The study objective was to investigate the relationship between metabolic disorders and thyroid autoantibodies in euthyroid subjects.

Methods: Data were obtained from a TIDE project survey of 55,891 subjects from 31 provinces in China. The body mass index(BMI), waist circumference(WC), blood pressure(BP), TPOAb, TgAb, TSH, UIC, blood glucose, lipid profile, uric acid(UA) levels were evaluated. FT4 and FT3 levels were measured in patients with abnormal serum TSH levels.

Results: In males, the BMI, WC, SBP, DBP, and OGTT2hPG of the TPOAb/TgAb-positive groups were significantly higher than those of the TPOAb/TgAb-negative groups. In females, the BMI, WC, SBP, DBP, TC, and LDL-C in the TPOAb/TgAb-positive groups were significantly increased compared to those in the TPOAb/TgAb-negative groups. Multivariate analysis showed that, in males, the OR of positive TgAb in the abdominal obesity group was 1.175 (95% CI 1.016-1.359, P for difference= 0.03), and the OR of positive TPOAb in the hyperuricemia group was 1.195 (95% CI 1.041-1.372, P for difference = 0.011). In females, the OR of positive TgAb was 1.19 (95% Cl 1.068-1.326, P for difference= 0.002) in the high LDL-C group.

Conclusions: Obesity, high LDL-C and hyperuricemia were positively correlated with the prevalence of positive thyroid autoantibodies in euthyroid subjects in a gender-dependent manner. This cross-sectional survey showed that metabolic disorders are associated with increased positive thyroid autoantibody levels in euthyroid subjects in a gender-dependent manner.
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http://dx.doi.org/10.4158/EP-2020-0008DOI Listing
April 2020

Effects of Saccharides from Arctium lappa L. Root on FeCl-Induced Arterial Thrombosis via the ERK/NF-B Signaling Pathway.

Oxid Med Cell Longev 2020 24;2020:7691352. Epub 2020 Mar 24.

Department of Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning Province, China.

Saccharides from Arctium lappa. L. root (ALR-S) is a high-purity fructosaccharide separated from the medicinal plant Arctium lappa. L. root. These compounds showed many pharmacological effects in previous studies. In the present study, the antithrombotic effects of ALR-S in arterial thrombosis via inhibiting platelet adhesion and rebalancing thrombotic and antithrombotic factor expression and secretion were found in rats and human aortic endothelial cells (HAECs). This study also showed that inhibition of oxidative stress (OS), which is closely involved in the expression of coagulation- and thrombosis-related proteins, was involved in the antithrombotic effects of ALR-S. Furthermore, studies using FeCl-treated HAECs showed that ALR-S induced the abovementioned effects at least partly by blocking the ERK/NF-B pathway. Moreover, U0126, a specific inhibitor of ERK, exhibited the same effects with ALR-S on a thrombotic process in FeCl-injured HAECs, suggesting the thrombotic role of the ERK/NF-B pathway and the antithrombotic role of blocking the ERK/NF-B pathway by ALR-S. In conclusion, our study revealed that the ERK/NF-B pathway is a potential therapeutic target in arterial thrombosis and that ALR-S has good characteristics for the cure of arterial thrombosis via regulating the ERK/NF-B signaling pathway.
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http://dx.doi.org/10.1155/2020/7691352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132581PMC
December 2020

The Presence of Serum TgAb Suggests Lower Risks for Glucose and Lipid Metabolic Disorders in Euthyroid General Population From a National Survey.

Front Endocrinol (Lausanne) 2020 18;11:139. Epub 2020 Mar 18.

Department of Endocrinology, Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital, Shanghai, China.

The expressions of antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) are very common in the sera of patients with autoimmune thyroid diseases (AITD). The relationship between thyroid autoantibodies and the occurrence of glucose and lipid metabolic disorders remains unclear. This study was performed to investigate the correlation between the presence of serum TPOAb/TgAb and those metabolic disorders in euthyroid general population. The data of this study were derived from the Thyroid Disease, Iodine status, and Diabetes National epidemiological (TIDE) survey from all 31 provinces of mainland China. A total of 17,964 euthyroid subjects including 5,802 males (4,000 with TPOAbTgAb and 1,802 with TPOAb/TgAb) and 12,162 females (8,000 with TPOAbTgAb and 4,162 with TPOAb/TgAb) were enrolled in this study. The blood glucose and lipid levels were compared between individuals with TPOAbTgAb and those with TPOAbTgAb, TPOAbTgAb, TPOAbTgAb. Both fasting blood glucose (FBG) concentration and the proportion of individuals with impaired FBG (IFG) showed the decreased trends in TPOAbTgAb males as compared with TPOAbTgAb men. There were significantly lower FBG and higher HDL-C levels as well as tendencies toward decreased incidences of IGT and hypertriglyceridemia in TPOAbTgAb females when compared with TPOAbTgAb women. Binary logistic regression analysis further showed that serum TgAb single positivity in males was an independent protective factor for IFG with an OR of 0.691 (95% CI, 0.503-0.949). For females, serum TgAb single positivity was an independent protective factor for hypertriglyceridemia with an OR of 0.859 (95% CI, 0.748-0.987). Trend test showed that with the increase of serum TgAb level, there were significant decreases in the prevalence of IFG among the men with TSH ≤ 2.5 mIU/L and that of hypertriglyceridemia in the women, especially among non-obese females. Serum TgAb single positivity may imply a reduced risk of IFG in euthyroid men and that of hypertriglyceridemia in euthyroid women. The mechanisms for the independent protective roles of TgAb await further investigation.
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http://dx.doi.org/10.3389/fendo.2020.00139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093715PMC
February 2021

U-Shaped Associations Between Urinary Iodine Concentration and the Prevalence of Metabolic Disorders: A Cross-Sectional Study.

Thyroid 2020 07 27;30(7):1053-1065. Epub 2020 Apr 27.

Department of Endocrinology and Metabolism, People's Hospital of Tibet Autonomous Region, Lhasa, P.R. China.

Iodine is important in both thyroid function and human metabolism. Studies have explored the effect of iodine on metabolic disorders through thyroid function. This study aimed to investigate the relationship between iodine status and metabolic disorders, such as metabolic syndrome (MetS), hypertension, impaired glucose metabolism, central obesity, and dyslipidemia. A total of 51,795 subjects aged ≥18 years from the TIDE (Thyroid Disorders, Iodine Status and Diabetes, a national epidemiological cross-sectional study) program were included. The prevalence of metabolic disorders and its related diseases was calculated based on the level of urinary iodine concentrations (UICs) using the chi-square method. To further explore whether the prevalence was associated with UIC, quadratic and UIC-stratified logistic regression models were used. The prevalence of metabolic disorders as a function of UIC was found to be U-shaped with a lower prevalence of 76.0% at an UIC of 300-499 μg/L. Participants with an UIC of 300-499 μg/L showed an association with metabolic disorders (odds ratio [OR] = 0.857, 95% confidence interval [CI 0.796-0.922]) and hypertension (OR = 0.873 [CI 0.814-0.936]). An UIC of 300-799 μg/L was found to be associated with the occurrence of MetS and impaired glucose tolerance. An UIC of 500-799 μg/L was associated with the occurrence of prediabetes (OR = 0.883 [CI 0.797-0.978]). An UIC of ≥300 μg/L was associated with the occurrence of hypertriglyceridemia, hypercholesterolemia, and high levels of low-density lipoprotein cholesterol. Furthermore, an UIC of <100 μg/L showed an association with hypertension (OR = 1.097 [CI 1.035-1.162]) and hypercholesterolemia (OR = 1.178 [CI 1.117-1.242]). The association between UICs in adults and metabolic disorders and its related diseases is U-shaped. The association between UIC and metabolic disorders disappears in cases of iodine deficiency (<100 μg/L) or excess (≥500 μg/L).
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http://dx.doi.org/10.1089/thy.2019.0516DOI Listing
July 2020

A negative association between urinary iodine concentration and the prevalence of hyperuricemia and gout: a cross-sectional and population-based study in Mainland China.

Eur J Nutr 2020 Dec 20;59(8):3659-3668. Epub 2020 Feb 20.

Department of Endocrinology, Qinghai Provincial People's Hospital, Xining, 810000, Qinghai, People's Republic of China.

Background And Aims: Iodine is one of the most important trace elements in the human body. It is not only the main component of thyroid hormones but also has extrathyroid biological functions. To date, there have been no large-scale epidemiological studies on the relationship between hyperuricemia and iodine intake, although both are closely related to health. A population-based epidemiological survey in China offers such an opportunity.

Methods: This population-based cross-sectional study recruited 75,653 adults aged ≥ 18 years from 2015 to 2017 with a randomized, multistage, stratified sampling strategy. Serum uric acid levels and urinary iodine concentrations (UICs) were measured.

Results: Stratified by UIC, the prevalence of hyperuricemia was 17.8%, 18.8%, 16.0% and 13.7% in the UIC < 100, 100-199, 200-299, and ≥ 300 μg/L groups, respectively; the prevalence of gout was 4.0%, 3.4%, 2.4% and 1.7%, respectively. The prevalence of gout decreased significantly as the UIC increased. The prevalence of hyperuricemia and gout were markedly higher in postmenopausal females than in the premenopausal population (hyperuricemia: 15.9% vs. 8.3%, X = 520.072, p < 0.001; gout: 3.6% vs. 1.3%, X = 219.889, p < 0.001), and the prevalence decreased as the UIC increased. Subjects in the more than adequate and excessive iodine groups had lower likelihoods of having hyperuricemia [aOR = 0.81 (95% CI 0.77-0.85), aOR = 0.68 (95% CI 0.64-0.72)] and lower odds of having gout than subjects in the adequate iodine (AI) group [aOR = 0.77 (95% CI 0.68-0.86), aOR = 0.59 (95% CI 0.51-0.68)].

Conclusions: UIC was inversely associated with the occurrence of hyperuricemia and gout. More in-depth research and prospective studies are needed to explore the molecular mechanisms and confirm the observed association.
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http://dx.doi.org/10.1007/s00394-020-02199-zDOI Listing
December 2020

Efficacy and Safety of Long-Term Universal Salt Iodization on Thyroid Disorders: Epidemiological Evidence from 31 Provinces of Mainland China.

Thyroid 2020 04 24;30(4):568-579. Epub 2020 Mar 24.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, P.R. China.

Mandatory universal salt iodization (USI) has been implemented in China for 20 years. Although iodine deficiency disorders are effectively controlled, the risk of excess iodine have been debated. A nationally representative cross-sectional study with 78,470 enrolled participants, aged 18 years or older, from all 31 provincial regions of mainland China was performed. The participants were given a questionnaire and underwent B-mode ultrasonography of the thyroid. Serum concentrations of thyroid hormones, thyroid antibodies, and urine iodine concentration (UIC) were measured. The median UIC of the adult population was 177.89 μg/L. The weighted prevalence of thyroid disorders in adults were as follows: 0.78% of overt hyperthyroidism, 0.44% of subclinical hyperthyroidism, 0.53% of Graves' disease, 1.02% of overt hypothyroidism, 12.93% of subclinical hypothyroidism, 14.19% of positive thyroid antibodies, 10.19% of positive thyroid peroxidase antibodies, 9.70% of positive thyroglobulin antibodies, 1.17% of goiter, and 20.43% of thyroid nodules. Iodine excess was only associated with higher odds of overt hyperthyroidism and subclinical hypothyroidism, while iodine deficiency was significantly associated with higher odds of most thyroid disorders. In addition, increased iodine intake was significantly associated with elevated serum thyrotropin levels but was inversely associated with thyroid antibodies and thyroid nodules. The long-term mandatory USI program with timely adjustments is successful in preventing iodine deficiency disorders, and it appears to be safe. The benefits outweigh the risks in a population with a stable median iodine intake level of up to 300 μg/L.
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http://dx.doi.org/10.1089/thy.2019.0067DOI Listing
April 2020

Selenoprotein S regulates adipogenesis through IRE1α-XBP1 pathway.

J Endocrinol 2020 03;244(3):431-443

Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.

The induction of endoplasmic reticulum (ER) stress is associated with adipogenesis, during which the inositol-requiring enzyme 1 alpha (IRE1α)-X-box-binding protein 1 (XBP1) pathway is involved. Selenoprotein S (SelS), which is an ER resident selenoprotein, is involved in ER homeostasis regulation; however, little is known about the role of SelS in regulating adipogenesis. In vivo studies showed that SelS protein levels in white adipose tissue were increased in obese subjects and high-fat diet (HFD)-fed mice. Moreover, we identified that SelS protein levels increased in the early phase of adipogenesis and then decreased in the late phase during adipogenesis. Overexpression of SelS promoted adipogenesis. Conversely, knockdown (KD) of SelS resulted in the inhibition of adipogenesis, which was related to increasing cell death, decreased mitotic clonal expansion, and cell cycle G1 arrest. In vivo studies also showed that ER stress markers (p-IRE1α/IRE1α, XBP1s, and Grp78) were significantly increased with upregulating of SelS expression in subcutaneous and visceral adipose tissues in the obese subjects and HFD-fed mice. Furthermore, in SelS KD cells, the levels of Grp78 were increased and the levels of p-IRE1α/IRE1α were unchanged , but mRNA levels of spliced XBP1 (XBP1s) produced by IRE1α-mediated splicing were decreased, suggesting a role of SelS in the modulation of IRE1α-XBP1 pathway. Moreover, inhibition of adipogenesis by SelS suppression can be rescued by overexpression of XBP1s. Thus, SelS appears to function as a novel regulator of adipogenesis through the IRE1α-XBP1 signaling pathway.
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http://dx.doi.org/10.1530/JOE-19-0292DOI Listing
March 2020

Intensive multifactorial intervention improved renal impairment in short-duration type 2 diabetes: A randomized, controlled, 7-year follow-up trial.

J Diabetes Complications 2020 01 14;34(1):107468. Epub 2019 Nov 14.

Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, PR China. Electronic address:

Aims: To investigate the effect of multifactorial intervention on the urinary albumin to creatinine ratio (UACR) and the estimated glomerular filtration rate (eGFR) in short-duration type 2 diabetes.

Methods: A total of 150 type 2 diabetes patients, with disease duration <1 year and with no evidence of atherosclerosis were randomized to either the intensive intervention group (IG, n = 75), or the conventional group (CG, n = 75) for 7 years. The predefined endpoint of microvascular complications was the progression of renal impairments (the development of albuminuria and the change of eGFR).

Results: The incidence of progression to albuminuria (UACR ≥30 mg/g) was 12% in IG and 28% in CG (HR 0.37, 95% CI: 0.19-0.70, P = .0025). eGFR was significantly lower in IG than that in CG in the year 2 (P = .043) and 3 (P = .032) follow-up. Sex, fasting plasma glucose (FPG), HbA1c, and systolic blood pressure (SBP) were independently associated with the UACR (β = -5.112, P = .015; β = 0.908, P = .045; β = 2.087, P = .038; and β = 2.787, P = .002, respectively); aging was independently associated with eGFR (β = -0.447, P = .000).

Conclusions: Intensive multifactorial intervention delayed the progression to albuminuria, and reduced eGFR rapidly in early stage of intervention in short-duration type 2 diabetes. FPG, HbA1c, and SBP were risk factors for UACR increase; aging was a risk factor for eGFR decline.
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http://dx.doi.org/10.1016/j.jdiacomp.2019.107468DOI Listing
January 2020

The antagonist of CXCR1 and CXCR2 protects mice from metabolic diseases through modulating inflammation.

Am J Physiol Endocrinol Metab 2019 12 1;317(6):E1205-E1217. Epub 2019 Oct 1.

Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.

Interleukin-8 (IL-8, also named CXCL8) binds to its receptors (CXCR1 and CXCR2) with subsequent recruitment of neutrophils and enhancement of their infiltration into inflamed sites, which exaggerates inflammation in many diseases. Recent studies have proposed that metabolic disorders can be attenuated by counteracting certain inflammatory signal pathways. In this study, we examined whether intervention with G31P, an antagonist of CXCL8, could attenuate tissue inflammation and development of metabolic disorders in mice. The and mice were subcutaneously injected with G31P or equivalent normal saline once a day for 6 wk. The physical and metabolic parameters, glucose tolerance, insulin sensitivity, hepatic lipid accumulation, and inflammation markers were measured. G31P improved hepatic insulin sensitivity by modulating expression of genes related to gluconeogenesis and phosphorylated Akt levels. The expressions of several genes encoding proteins involved in de novo lipogenesis were decreased in G31P-treated mice. Meanwhile, immune cell infiltration and cytokine release were attenuated in mice with G31P treatment. G31P also improved the ratio of proinflammatory M1 and anti-inflammatory M2 macrophages. Furthermore, G31P ameliorates metabolic disturbances via inhibition of CXCR1 and CXCR2 pathways in mice. These data suggest that the selective inhibition of CXC chemokines may have therapeutic effects on symptoms associated with obesity and diabetes.
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http://dx.doi.org/10.1152/ajpendo.00117.2019DOI Listing
December 2019

Specific Inhibition of CYP4A Alleviates Myocardial Oxidative Stress and Apoptosis Induced by Advanced Glycation End-Products.

Front Pharmacol 2019 9;10:876. Epub 2019 Aug 9.

College of Pharmacy, Dalian Medical University, Dalian, China.

High exposure to advanced glycation end-products (AGEs) may induce cardiotoxicity. However, the effects and mechanisms remain to be further clarified. CYP4A plays an important role in the pathophysiological process of myocardial abnormalities by modulating oxidative stress and apoptosis (OS/Apop) signaling pathway. The present work aimed to investigate whether CYP4A mediates AGEs-induced myocardial injury. AGEs solution was administered intragastrically to C57BL/6 mice for 60 days, while the specific inhibitor of CYP4A, HET0016, was given from the 47th day intraperitoneal injection for 2 weeks. Levels of OS/Apop in heart tissue were measured. The effects on the cell viability and apoptosis were detected in primary rat cardiomyocytes. To further investigate the mechanism, H9c2 cells were treated with HET0016 or small interfering RNAs (siRNAs) against CYP4a mRNA before incubation with AGEs. Exposure to AGEs led to significantly increased expression of CYP4A and levels of OS/Apop in heart and H9c2 cells both and . The OS/Apop pathway was activated with increased expression of NOX2, p-JNK, and cleaved caspase-3 (c-caspase-3) and decreased expression of p-Akt and Bcl-xL both and . Specific CYP4A suppression by HET0016 or siRNA exerted significant protective effects by attenuating AGEs-induced OS/Apop pathways . Our results demonstrate that specific inhibition of CYP4A might be a potential therapeutic option for myocardial injury induced by AGEs.
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http://dx.doi.org/10.3389/fphar.2019.00876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696796PMC
August 2019

O-GlcNAcylation in immunity and inflammation: An intricate system (Review).

Int J Mol Med 2019 Aug 11;44(2):363-374. Epub 2019 Jun 11.

Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.

Chronic, low‑grade inflammation associated with obesity and diabetes result from the infiltration of adipose and vascular tissue by immune cells and contributes to cardiovascular complications. Despite an incomplete understanding of the mechanistic underpinnings of immune cell differentiation and inflammation, O‑GlcNAcylation, the addition of O‑linked N‑acetylglucosamine (O‑GlcNAc) to cytoplasmic, nuclear and mitochondrial proteins by the two cycling enzymes, the O‑linked N‑acetylglucosamine transferase (OGT) and the O‑GlcNAcase (OGA), may contribute to fine‑tune immunity and inflammation in both physiological and pathological conditions. Early studies have indicated that O‑GlcNAcylation of proteins play a pro‑inflammatory role in diabetes and insulin resistance, whereas subsequent studies have demonstrated that this post‑translational modification could also be protective against acute injuries. These studies suggest that diverse types of insults result in dynamic changes to O‑GlcNAcylation patterns, which fluctuate with cellular metabolism to promote or inhibit inflammation. In this review, the current understanding of O‑GlcNAcylation and its adaptive modulation in immune and inflammatory responses is summarized.
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http://dx.doi.org/10.3892/ijmm.2019.4238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605495PMC
August 2019

Efficacy and safety of sitagliptin added to metformin and insulin compared with voglibose in patients with newly diagnosed type 2 diabetes.

Clinics (Sao Paulo) 2019 29;74:e736. Epub 2019 Apr 29.

Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, PR China.

Objective: To assess the efficacy and safety of sitagliptin compared with voglibose added to combined metformin and insulin in patients with newly diagnosed type 2 diabetes (T2DM).

Methods: In this 12-week prospective, randomized, parallel trial, 70 newly diagnosed T2DM patients with glycosylated hemoglobin (HbA1c) ≥9% and/or fasting plasma glucose (FPG) ≥11.1 mmol/L were randomized (1:1) to receive sitagliptin 100 mg per day + metformin + insulin glargine or voglibose 0.2 mg three times daily + metformin + insulin glargine. Change in HbA1c at week 12 was the primary endpoint.

Results: The mean baseline HbA1c was 11.0% in the patients. The changes in HbA1c from baseline were -6.00% in the sitagliptin group and -3.58% in the voglibose group, and the between-group difference was -2.42% (95% CI -1.91 to -2.93, p=0.02). The differences in FPG and homeostatic model assessment of β-cell function (HOMA-β) and the change in body weight between groups from baseline were -2.95 mmol/L (p=0.04), 43.91 (p=0.01) and -2.23 kg (p=0.01), respectively. One patient (2.9%) in the sitagliptin group and three patients (8.6%) in the voglibose group exhibited hypoglycemia.

Conclusions: Sitagliptin added to combined metformin and insulin therapy showed greater efficacy and good safety regarding hypoglycemia in patients with newly diagnosed T2DM compared with voglibose.
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http://dx.doi.org/10.6061/clinics/2019/e736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474317PMC
December 2019

Comparison of a twice daily injection of insulin aspart 50 with insulin aspart 30 in patients with poorly controlled type 2 diabetes.

Curr Med Res Opin 2019 06 14;35(6):1091-1096. Epub 2019 Jan 14.

a Department of Endocrinology , The First Affiliated Hospital of Dalian Medical University , Dalian , PR China.

Objective: To compare the efficacy and safety of a twice daily injection of insulin aspart (BIAsp) 30 and BIAsp50 in patients with type 2 diabetes mellitus (T2DM) poorly controlled with oral hypoglycemic agents (OHAs).

Methods: In this 12 week prospective, randomized, parallel trial, a total of 80 T2DM patients, 59 ± 10 years old with a disease duration of 9.3 ± 6.6 years and HbA1c >7% despite large doses of metformin and sulfonylurea administration, were randomized to receive BIAsp30 (n = 40) or BIAsp50 (n = 40). The primary endpoint was a change in HbA1c at week 12.

Results: The changes in HbA1c from baseline were -2.5% ± 1.0% in the BIAsp50 group and -2.5% ± 1.2% in the BIAsp30 group (p = .897). No difference was observed in the rate of HbA1c target achievement (<7.0%) between BIAsp50 (42.5%) and BIAsp30 (32.5%) (p = .495). The change in fasting plasma glucose (FPG) in the BIAsp50 group was lower than that in the BIAsp30 group (p < .001), while the change in two-hour postprandial blood glucose (2hPBG) was higher and blood glucose excursion was lower in the BIAsp50 group than that in the BIAsp30 group (p < .001, p < .001). A significant improvement in HbA1c was observed with BIAsp50 in subgroups with baseline blood glucose excursion >7.8 mmol/L or 2hPBG >17.6 mmol/L compared with BIAsp30. There were no differences in hypoglycemia or body weight between groups.

Conclusions: Compared with BIAsp30, BIAsp50 showed greater efficacy in patients with baseline BG excursion >7.8 mmol/L or 2hPBG >17.6 mmol/L as well as good safety for hypoglycemia.

Clinical Trial Registration: ChiCTR-IIR-16008958.
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http://dx.doi.org/10.1080/03007995.2018.1558853DOI Listing
June 2019

Selenoprotein S protects against high glucose-induced vascular endothelial apoptosis through the PKCβII/JNK/Bcl-2 pathway.

J Cell Biochem 2018 Nov 28. Epub 2018 Nov 28.

Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.

Vascular endothelial apoptosis is closely associated with the pathogenesis and progression of diabetic macrovascular diseases. Selenoprotein S (SelS) participates in the protection of vascular endothelial and smooth muscle cells from oxidative and endoplasmic reticulum stress-induced injury. However, whether SelS can protect vascular endothelium from high glucose (HG)-induced apoptosis and the underlying mechanism remains unclear. The present study preliminarily analyzed aortic endothelial apoptosis and SelS expression in diabetic rats in vivo and the effects of HG on human umbilical vein endothelial cell (HUVEC) apoptosis and SelS expression in vitro. Subsequently, SelS expression was up- or downregulated in HUVECs using the pcDNA3.1-SelS recombinant plasmid and SelS-specific small interfering RNAs, and the effects of high/low SelS expression on HG-induced HUVEC apoptosis and a possible molecular mechanism were analyzed. As expected, HG induced vascular endothelial apoptosis and upregulated endothelial SelS expression in vivo and in vitro. SelS overexpression in HUVECs suppressed HG-induced increase in apoptosis and cleaved caspase3 level, accompanied by reduced protein kinase CβII (PKCβII), c-JUN N-terminal kinase (JNK), and B-cell lymphoma/leukemia-2 (Bcl-2) phosphorylation. In contrast, inhibiting SelS expression in HUVECs further aggravated HG-induced increase in apoptosis and cleaved caspase3 level, which was accompanied by increased PKCβII, JNK, and Bcl-2 phosphorylation. Pretreatment with PKC activators blocked the protective effects of SelS and increased the apoptosis and cleaved caspase3 level in HUVECs. In summary, SelS protects vascular endothelium from HG-induced apoptosis, and this was achieved through the inhibition of PKCβII/JNK/Bcl-2 pathway to eventually inhibit caspase3 activation. SelS may be a promising target for the prevention and treatment of diabetic macrovascular complications.
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http://dx.doi.org/10.1002/jcb.28154DOI Listing
November 2018

Decreased Thyroid Peroxidase Antibody Titer in Response to Selenium Supplementation in Autoimmune Thyroiditis and the Influence of a Selenoprotein P Gene Polymorphism: A Prospective, Multicenter Study in China.

Thyroid 2018 12;28(12):1674-1681

The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, China.

Recent intervention studies have suggested that selenium (Se) is an effective treatment for autoimmune thyroiditis (AIT). However, the exact effect of Se on AIT is unclear as well as the mechanism of action. The aim of the present study was to explore the effect of Se on thyroid peroxidase antibody (TPOAb) titers in patients with AIT and to analyze the potential impact of the genetic background on the effect of Se supplementation. This was a randomized, placebo-controlled, double-blind trial. Three hundred and sixty-four patients with elevated TPOAb (>300 IU/mL) were recruited and randomized to receive Se yeast 200 μg/day supplementation or placebo. Urinary iodine concentration, serum thyrotropin, free thyroxine, TPOAb, Se, malondialdehyde, and serum glutathione peroxidase activity were measured at baseline and follow-up. Ninety-six patients were genotyped for single nucleotide polymorphism r25191G/A in the selenoprotein P ( gene. The median urinary iodine concentration was 182 μg/L. Serum Se increased significantly ( < 0.001) after Se treatment. TPOAb titer decreased by 10.0% at 3 months and by 10.7% at 6 months after Se supplementation, while there was a moderate increase in TPOAb titers over the follow-up period in patients receiving placebo. Glutathione peroxidase activity significantly increased ( < 0.001), and malondialdehyde significantly decreased ( < 0.001) after 6 months of Se supplementation. TPOAb titers decreased to variable extents in patients with different genotypes of single nucleotide polymorphism r25191G/A after Se supplementation. Serum TPOAb titers in patients with the AA genotype showed a more significant decrease (by 46.2%) than those with the GA and GG genotypes (by 14.5 and 9.8% respectively) at 3 months of Se supplementation ( = 0.070). Se supplementation significantly reduced TPOAb titers in patients with AIT, and there may be an important genetic component influencing interindividual differences in the decrease in TPOAb titers.
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http://dx.doi.org/10.1089/thy.2017.0230DOI Listing
December 2018

Selenoprotein S protects against adipocyte death through mediation of the IRE1α-sXBP1 pathway.

Biochem Biophys Res Commun 2018 09 24;503(4):2866-2871. Epub 2018 Aug 24.

Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. Electronic address:

As the most conserved branch of the unfolded protein response (UPR), the inositol-requiring enzyme 1a (IRE1a)/X-box binding protein 1 (XBP1) pathway plays crucial roles in cell survival and cell death by upregulating UPR-associated genes involved in protein entry into the endoplasmic reticulum (ER) and ER-associated degradation (ERAD). Selenoprotein S (SelS) is localized to the ER membrane and involved in ERAD. Although SelS plays an important role in restoring ER stress, the SelS-dependent protective mechanisms against cell death remain unclear. Here, using an inducible SelS knockdown (KD) 3T3-L1 cell model, we showed that SelS KD resulted adipocyte death, which was associated with imbalance of the Bcl-2 family members. Furthermore, SelS KD decreased spliced XBP1 (sXBP1), increased IRE1α and p-JNK, suggesting a role of SelS in the modulation of the IRE1α-sXBP1 pathway. Moreover, adipocyte death induced by SelS suppression can be inhibited by overexpression of sXBP1. Thus, it is proposed that SelS promotes cell survival through the IRE1α-XBP1 signaling pathway.
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http://dx.doi.org/10.1016/j.bbrc.2018.08.057DOI Listing
September 2018

Iron Deficiency May Predict Greater Risk for Hypothyroxinemia: A Retrospective Cohort Study of Pregnant Women in China.

Thyroid 2018 08 30;28(8):968-975. Epub 2018 Jul 30.

1 Department of Endocrinology and Metabolism, Endocrine Institute, and Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University , Shenyang, China .

Background: Pregnant women are highly vulnerable to iron deficiency (ID) due to the increased iron needs during pregnancy. ID decreases circulating thyroid hormone concentrations likely through impairment of iron-dependent thyroid peroxidase. The present study aimed to explore the association between ID and hypothyroxinemia in a retrospective cohort of pregnant women in China.

Methods: To investigate the relationship between ID and hypothyroxinemia, 723 pregnant women were retrospectively analyzed, including 675 and 309 women in the second and third trimesters, respectively. Trimester-specific hypothyroxinemia was defined as free thyroxine (fT4) levels below the 2.5th percentile of the reference range with normal serum thyrotropin (TSH) or TSH higher than the 97.5th percentile of the reference range in each trimester of pregnancy. Serum TSH, fT4, thyroid peroxidase antibodies, thyroglobulin antibodies, serum ferritin, soluble transferrin receptor, and urinary iodine concentrations were measured. Serum ferritin, soluble transferrin receptor, and total body iron were used to indicate the nutritional iron status.

Results: Cross-sectional multiple linear regression analysis showed that iron status was positively associated with serum fT4 levels in the first and second trimesters of pregnancy, but not in the third trimester. Logistic regression analysis showed that ID was an independent risk factor for hypothyroxinemia (odds ratio = 14.86 [confidence interval 2.31-95.81], p = 0.005 in the first trimester and odds ratio = 3.36 [confidence interval 1.01-11.21], p = 0.048 in the second trimester). The prospective analysis showed that pregnant women with ID during the first trimester of pregnancy had lower serum fT4 levels and a higher rate of hypothyroxinemia in the second or third trimester than those without ID.

Conclusions: ID appears to be a risk factor to predict hypothyroxinemia in the first and second trimesters of pregnancy, but not in the third trimester. Pregnant women with ID in the first and second trimesters should be regarded as a high-risk group for maternal hypothyroxinemia.
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http://dx.doi.org/10.1089/thy.2017.0491DOI Listing
August 2018

A case series study of hypopituitarism in older patients with and without gastrointestinal symptoms.

Postgrad Med 2018 Jun 4;130(5):501-506. Epub 2018 Jun 4.

c Department of Endocrinology , First Affiliated Hospital of Dalian Medical University , Dalian , China.

Objectives: Some older individuals who present with gastrointestinal symptoms as their chief complaint were ultimately diagnosed with hypopituitarism instead of gastrointestinal diseases. The aim of this study was to find the characteristics of biochemical indicators in these patients so as to reduce early misdiagnosis.

Methods: We conducted a retrospective review of 45 patients with hypopituitarism who were at least 60 years of age. Two groups were included: group of hypopituitarism patients with gastrointestinal symptoms (Group G) included 23 patients with gastrointestinal symptoms and group of hypopituitarism patients without gastrointestinal symptoms (Group N) included 22 patients without these symptoms. In Group G, we investigated the prevalence of different gastrointestinal symptoms, the response of these symptoms to treatment, the occurrence of electrolyte disorders, and target gland dysfunction. Then, we compared the electrolyte and target gland function indices between the two groups.

Results: Nausea and vomiting were the most common complaints, accounting for 69.57% of the gastrointestinal symptoms in Group G. Hyponatremia was the most common electrolyte disorder, occurring in 72.86% (n = 18) of patients in Group G. Hypoadrenalism and hypothyroidism were reported by 69.57% and 60.78% of patients, respectively, in Group G. None of the gastrointestinal symptoms were relieved by 4 weeks of treatment with antacid and motility drugs. As mentioned, 18 patients also experienced refractory hyponatremia during early treatment including regular sodium supplements; however, their gastrointestinal symptoms and hyponatremia improved after only a week of treatment for hypopituitarism. Regarding the biochemical indicators, only serum sodium and cortisol in Group G were statistically lower compared with those in Group N (P < .05).

Conclusion: Nausea and vomiting were the most common gastrointestinal symptoms in older patients with hypopituitarism, which were associated with lower serum sodium and cortisol. In addition, we hope to share the research to our gastroenterologists that serum sodium and cortisol should be tested when meeting elder patients with unexplained gastrointestinal symptoms.
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http://dx.doi.org/10.1080/00325481.2018.1479612DOI Listing
June 2018

Selenoprotein S Attenuates Tumor Necrosis Factor--Induced Dysfunction in Endothelial Cells.

Mediators Inflamm 2018 1;2018:1625414. Epub 2018 Apr 1.

Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China.

Endothelial dysfunction, partly induced by inflammatory mediators, is known to initiate and promote several cardiovascular diseases. Selenoprotein S (SelS) has been identified in endothelial cells and is associated with inflammation; however, its function in inflammation-induced endothelial dysfunction has not been described. We first demonstrated that the upregulation of SelS enhances the levels of nitric oxide and endothelial nitric oxide synthase in tumor necrosis factor- (TNF-) -treated human umbilical vein endothelial cells (HUVECs). The levels of TNF--induced endothelin-1 and reactive oxygen species are also reduced by the upregulation of SelS. Furthermore, SelS overexpression blocks the TNF--induced adhesion of THP-1 cells to HUVECs and inhibits the increase in intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Moreover, SelS overexpression regulates TNF--induced inflammatory factors including interleukin-1, interleukin-6, interleukin-8, and monocyte chemotactic protein-1 and attenuates the TNF--induced activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-B (NF-B) pathways. Conversely, the knockdown of SelS with siRNA results in an enhancement of TNF--induced injury in HUVECs. These findings suggest that SelS protects endothelial cells against TNF--induced dysfunction by inhibiting the activation of p38 MAPK and NF-B pathways and implicates it as a possible modulator of vascular inflammatory diseases.
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http://dx.doi.org/10.1155/2018/1625414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901950PMC
October 2018

Atherosclerosis associated with dynamic inflammation changes after multifactorial intervention in short-duration type 2 diabetes: A randomized, controlled, 10-year follow-up trial.

J Diabetes Complications 2017 Aug 25;31(8):1286-1292. Epub 2017 May 25.

Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, PR China. Electronic address:

Purpose: To analyze the impact of dynamic changes in inflammation on atherosclerosis in short-duration type 2 diabetes after multifactorial intervention.

Methods: In this randomized controlled study, a total of 150 type 2 diabetes patients who had a mean age of 49.8±7.3years, 51% male, with disease duration <1year and without evidence of atherosclerosis were randomized into an intensive intervention group (IG), in which patients received multiple risk factors intervention by the special project team and tried to reach the pre-determined intervention goals, and a conventional group (CG), in which patients received standard diabetes care by the clinic doctor. All patients recieved intervention study for 7 years, then underwent a 3-year observational follow-up study. The primary endpoints were occurrence of subclinical atherosclerosis, defined as the intima-media thickness of the common carotid artery (CC-IMT)≥1.0mm or formation of atherosclerosis plaques, and the occurrence of cardiovascular events.

Results: 68 patients in IG and 65 patients in CG completed the 10-year study. The cumulative incidence of subclinical atherosclerosis was 30.7% vs 57.3% (IG vs CG, HR 0.36, 95% CI 0.22-0.60, P<0.0001) and that of cardiovascular events was 12.0% vs 22.7% (IG vs CG, HR 0.46, 95% CI 0.21-0.98, P=0.0516). High sensitivity C-reactive protein (hs-CRP) reduction from baseline to the 10-year follow-up was -1.54mg/L (IG) and -0.67mg/L (CG) with difference (IG minus CG) of -0.87mg/L(95% CI -0.72 to -1.02, P=0.008) and the natural logarithm of serum amyloid A (SAA) reduction was -4.04 (IG) and -1.44 (CG) with difference (IG minus CG) of -2.60 (95% CI -2.30 to -2.90, P=0.002). The decrease in general score of inflammatory markers (combination of hs-CRP and SAA) was independently associated with subclinical atherosclerosis (OR=0.65, P=0.045) and cardiovascular events (OR=0.60, P=0.042).

Conclusions: Dynamic changes in inflammation act as an important factor that affects the occurrence of atherosclerosis in type 2 diabetes patients. Multifactorial intensive intervention can reduce systemic low-grade inflammation and delay the occurrence of atherosclerosis in short-duration type 2 diabetes.
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http://dx.doi.org/10.1016/j.jdiacomp.2017.05.008DOI Listing
August 2017

CXCL8 Antagonist Improves Diabetic Nephropathy in Male Mice With Diabetes and Attenuates High Glucose-Induced Mesangial Injury.

Endocrinology 2017 06;158(6):1671-1684

Department of Immunology, Dalian Medical University, Dalian 116011, Liaoning, China.

Inflammation is recognized as a crucial contribution to diabetic nephropathy (DN). CXCL8 binds to its CXC chemokine receptors (CXCR1 and CXCR2) for recruiting neutrophil infiltration and initiates tissue inflammation. Therefore, we explored the effect of CXCR1 and CXCR2 inhibition on DN. This was achieved by CXCL8(3-72)K11R/G31P (G31P), an antagonist of CXCL8 that has exhibited therapeutic efficacy in inflammatory diseases and malignancies. In this study, we found that renal leukocyte accumulation and rapid increases of CXCL8 occurred in high-fat diet/streptozocin-induced diabetic mice. G31P effectively reduced urine volume, urine albumin/creatinine ratio, blood urea nitrogen, and creatinine clearance rate in mice with diabetes. In addition, renal histopathologic changes including mesangial expansion, glomerulosclerosis, and extracellular matrix deposition were partially moderated in G31P-treated diabetic mice. Furthermore, G31P attenuated renal inflammation and renal fibrosis of diabetic mice by inhibiting proinflammatory and profibrotic elements. G31P also inhibited high glucose-induced inflammatory and fibrotic factor upregulation in human renal mesangial cells. At the molecular level, G31P inhibited activation of CXCR1/2 downstream signaling JAK2/STAT3 and ERK1/2 pathways in in vitro and in vivo experiments. Our results suggest blockade of CXCR1/2 by G31P could confer renoprotective effects that offer potential therapeutic opportunities in DN.
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http://dx.doi.org/10.1210/en.2016-1781DOI Listing
June 2017

High dietary selenium intake is associated with less insulin resistance in the Newfoundland population.

PLoS One 2017 5;12(4):e0174149. Epub 2017 Apr 5.

Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.

As an essential nutrient, Selenium (Se) is involved in many metabolic activities including mimicking insulin function. Data on Se in various biological samples and insulin resistance are contradictory, moreover there is no large study available regarding the relationship of dietary Se intake with insulin resistance in the general population. To investigate the association between dietary Se intake and variation of insulin resistance in a large population based study, a total of 2420 subjects without diabetes from the CODING (Complex Diseases in the Newfoundland Population: Environment and Genetics) study were assessed. Dietary Se intake was evaluated from the Willett Food Frequency questionnaire. Fasting blood samples were used for the measurement of glucose and insulin. Insulin resistance was determined with the homeostasis model assessment (HOMA-IR). Body composition was measured using dual energy X-ray absorptiometry. Analysis of covariance showed that high HOMA-IR groups in both males and females had the lowest dietary Se intake (μg/kg/day) (p < 0.01), being 18% and 11% lower than low HOMA-IR groups respectively. Insulin resistance decreased with the increase of dietary Se intake in females but not in males after controlling for age, total calorie intake, physical activity level, serum calcium, serum magnesium, and body fat percentage (p < 0.01). Partial correlation analysis showed that dietary Se intake was negatively correlated with HOMA-IR after adjusting for the Se confounding factors in subjects whose dietary Se intake was below 1.6 μg/kg/day (r = -0.121 for males and -0.153 for females, p < 0.05). However, the negative correlation was no longer significant when dietary Se intake was above 1.6 μg/kg/day. Our findings suggest that higher dietary Se intake is beneficially correlated with lower insulin resistance when total dietary Se intake was below 1.6 μg/kg/day. Above this cutoff, this beneficial effect disappears.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174149PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381811PMC
August 2017

Efficacy and safety of linagliptin/metformin single-pill combination as initial therapy in drug-naïve Asian patients with type 2 diabetes.

Diabetes Res Clin Pract 2017 Feb 5;124:48-56. Epub 2016 Dec 5.

Boehringer Ingelheim International Trading Co., Ltd., 29/F, Park Place, 1601 Nanjing Road (West), Shanghai 200040, China.

Aim: To assess efficacy/safety of initial linagliptin/metformin single-pill combination (SPC) therapies versus individual drug components over 24weeks in treatment-naïve Asian patients with type 2 diabetes mellitus and insufficient glycemic control.

Methods: Patients (initial glycated hemoglobin [HbA1c] ⩾7.5% to <11.0% [58-97mmol/mol]; main group) were randomized to: linagliptin 5mg once daily (qd); metformin 500mg twice daily (bid); metformin 1000mg bid; linagliptin 2.5mg/metformin 500mg bid; or linagliptin 2.5mg/metformin 1000mg bid. Patients with severe hyperglycemia (HbA1c ⩾11.0% [97mmol/mol]) received linagliptin 2.5mg/metformin 1000mg bid or linagliptin 5mg qd (switched at week 12 from linagliptin to SPC if HbA1c >8.0% [64mmol/mol]). The main group primary endpoint was HbA1c change from baseline to week 24.

Results: At week 24, adjusted mean change from baseline in HbA1c (main group, n=733) was: linagliptin 5mg qd, -1.3%; metformin 500mg bid, -1.6%; metformin 1000mg bid, -2.1%; linagliptin 2.5mg/metformin 500mg bid, -2.2%; linagliptin 2.5mg/metformin 1000mg bid, -2.3%. The first test of primary HbA1c analysis (linagliptin 2.5mg/metformin 1000mg bid vs. metformin 1000mg bid) was borderline non-significant; however, SPCs produced significantly greater reductions in HbA1c from baseline versus respective monotherapies in all but one pre-defined sensitivity analysis. In the severe hyperglycemia group (n=143), linagliptin 2.5mg/metformin 1000mg bid produced a superior HbA1c reduction (-4.7%) versus linagliptin 5mg qd (-3.5%) after 12weeks. Hypoglycemic adverse events were low across groups.

Conclusions: Initial linagliptin/metformin SPC significantly improved glycemic control in this population.
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http://dx.doi.org/10.1016/j.diabres.2016.11.026DOI Listing
February 2017