Association between the triglyceride-glucose index and thyroid disorders: a cross-sectional survey and Mendelian randomization analysis.

BACKGROUND: Metabolic diseases are associated with thyroid disorders. Insulin resistance is the common pathological basis of metabolic diseases. We explored the relationship between the triglyceride-glucose (TyG) index, a simple insulin-resistance marker, and thyroid disorders. METHODS: Eligible TIDE (Thyroid Diseases, Iodine Status and Diabetes Epidemiology) subjects (n = 47,710) were screened with inclusion/exclusion criteria. Thyroid disorder prevalence among different TyG index groups was stratified by sex. Logistic regression evaluated the correlation between the TyG index and thyroid disorders. Multiple linear regression evaluated the association between the TyG index and TSH. Additionally, two-sample Mendelian randomization (MR) using published genome-wide association study data evaluated causality in the association between the TyG index and TSH. RESULTS: Men and women with greater TyG indices had a significantly greater prevalence of thyroid disorders than individuals with the lowest quartile (Q1) of TyG index (p < 0.05). Following adjustment for confounding factors, we observed that a greater TyG index significantly increased the risk of subclinical hypothyroidism in men and women (men: Q2: odds ratio (OR) [95% confidence interval (CI)] = 1.22 [1.07-1.38], p = 0.002; Q3: OR [95% CI] = 1.28 [1.12-1.45], p < 0.001; Q4: OR [95% CI] = 1.29 [1.12-1.50], p = 0.001; women: Q2: OR [95% CI] = 1.25 [1.12-1.39], p < 0.001; Q3: OR [95% CI] = 1.47 [1.31-1.64], p < 0.001; Q4: OR [95% CI] = 1.61 [1.43-1.82], p < 0.001). Only among women was the highest TyG index quartile associated with hypothyroidism (OR [95% CI] = 1.70 [1.15-2.50], p = 0.007). Additionally, in men, the association exists only in the more than adequate iodine intake population. In women, the relationship between the TyG index and thyroid disorders disappears after menopause. Furthermore, the TyG index exhibited a linear positive correlation with TSH levels. The MR analysis results revealed a causal relationship between a genetically determined greater TyG index and increased TSH (inverse-variance weighting (IVW): OR [95% CI] = 1.14 [1.02-1.28], p = 0.020); however, this causal relationship disappeared after adjusting for BMI in multivariable MR (MVMR) analysis (MVMR-IVW: OR 1.03, 95% CI 0.87-1.22, p = 0.739). CONCLUSIONS: A greater TyG index is associated with hypothyroidism and subclinical hypothyroidism and varies by sex and menopausal status. MR analysis demonstrated that the causal relationship between a genetically determined greater TyG index and elevated TSH levels is confounded or mediated by BMI.

Global, regional, and national burden of type 1 diabetes in adolescents and young adults.

BACKGROUND: Type 1 diabetes (T1D) incidence in adolescents varies widely, but has increased globally in recent years. This study reports T1D burden among adolescents and young adults aged 10-24-year-old age group at global, regional, and national levels. METHODS: Based on the Global Burden of Disease Study 2019, we described the burden of T1D in the 10-24-year-old age group. We further analyzed these trends by age, sex, and the Social Development Index. Joinpoint regression analysis was used to assess temporal trends. RESULTS: T1D incidence among adolescents and young adults increased from 7·78 per 100,000 population (95% UI, 5·27-10·60) in 1990 to 11·07 per 100,000 population (95% UI, 7·42-15·34) in 2019. T1D mortality increased from 5701·19 (95% UI, 4642·70-6444·08) in 1990 to 6,123·04 (95% UI, 5321·82-6887·08) in 2019, representing a 7·40% increase in mortality. The European region had the highest T1D incidence in 2019. Middle-SDI countries exhibited the largest increase in T1D incidence between 1990 and 2019. CONCLUSION: T1D is a growing health concern globally, and T1D burden more heavily affects countries with low SDI. Specific measures and effective collaboration among countries with different SDIs are required to improve diabetes care in adolescents. IMPACT: We assessed trends in T1D incidence and burden among youth in the 10-24-year-old age group by evaluating data from the Global Burden of Disease Study 2019. Our results demonstrated that global T1D incidence in this age group increased over the past 30 years, with the European region having the highest T1D incidence. Specific measures and effective collaboration among countries with different SDIs are required to improve diabetes care in adolescents.

Changes in the prevalence of diabetes and control of risk factors for diabetes among Chinese adults from 2007 to 2017: An analysis of repeated national cross-sectional surveys.

INTRODUCTION: To examine changes in the prevalence of diabetes and the control of risk factors for diabetes over 10 years among adults in China. METHODS: Two population-based cross-sectional surveys were used to obtain a nationally representative sample of adults aged 20 years and older in mainland China in 2007 (n = 46 239) and 2017 (n = 73 340). Changes in the prevalence of diabetes, impaired fasting glucose, impaired glucose tolerance, and prediabetes, as diagnosed by the World Health Organization criteria, were assessed over time. RESULTS: The weighted prevalence of diagnosed diabetes (3.8% vs 6.3%, p = .0001) and total diabetes (9.7% vs 11.7%, p = .005) increased among the overall population between 2007 and 2017. The weighted prevalence of undiagnosed diabetes (5.9% vs 5.4%, p = .7), impaired fasting glucose (2.7% vs 2.6%, p = .68), impaired glucose tolerance (12.7% vs 12.5%, p = .95), prediabetes (15.4% vs 15.1%, p = .79), the treatment of diabetes (34.1% vs 32.5%, p = .44), and the control of diabetes (31.1% vs 32.8%, p = .73) did not significantly change over this period. The awareness of diabetes (39.4% vs 53.6%, p = .0004) increased over 10 years among the overall population. The proportion of achieved high-density lipoprotein cholesterol targets increased (p = .005), but the proportion of achieved body mass index (p = .01) and waist circumference (p = .0002) targets decreased significantly. CONCLUSIONS: Between 2007 and 2017, the prevalence of total diabetes (diagnosed by the World Health Organization criteria), especially diagnosed diabetes, increased among adults in China. Although awareness of diabetes improved, effective interventions and clinical strategies are urgently required.

Iodine-induced thyroid dysfunction: a scientometric study and visualization analysis.

Objective: Iodine is essential in thyroid hormone production. Iodine deficiency is associated with serious complications (i.e miscarriage and stillbirth), whereas excess can cause thyroid dysfunction (i.e hyperthyroidism, hypothyroidism, thyroid autoimmunity). We conducted this scientometric study to visualize hot spots and trends in iodine-induced thyroid dysfunction over past two decades. The aim of this paper was to help scholars quickly understand the development and potential trend in this field, and guide future research directions. Methods: Articles on iodine-induced thyroid dysfunction from 2000 to 2022 were retrieved from the Web of Science Core Collection (WoSCC) using the following search terms: (((((TS=(hypothyroid*)) OR TS=(hyperthyroid*)) OR TS= ("TSH deficiency")) OR TS= ("thyroid stimulating hormone deficiency")) AND TS=(Iodine)) NOT TS=(radioiodine). Only publications in English were selected. CiteSpace, VOSviewer, Tableau, Carrot2, and R software were used to analyze the contribution and co-occurrence relationships of different countries, institutes, keywords, references, and journals. Results: A total of 2986 publications from 115 countries and 3412 research institutions were included. From 2000 to 2022, research on iodine-induced thyroid dysfunction progressed over a three-stage development period: initial development (2000-2009), stable development (2010-2016), and rapid development (2016-2022) period. The Journal of Clinical Endocrinology and Metabolism had the most co-citations followed and China Medical University (n=76) had the most publications. The top three clusters of co-citation references were isolated maternal hypothyroxinemia, subclinical hyperthyroidism, and brain development. Various scientific methods were applied to reveal acknowledge structure, development trend and research hotspots in iodine-induced thyroid dysfunction. Conclusion: Our scientometric analysis shows that investigations related to pregnant women, epidemiology surveys, and iodine deficiency are promising topics for future iodine-induced thyroid dysfunction research and highlights the important role of iodine on thyroid function.

Subclinical hypothyroidism increases insulin resistance in normoglycemic people.

Objective: To investigate the effect of simple subclinical hypothyroidism (SCH) and type 2 diabetes mellitus (T2DM) combined with SCH on insulin resistance. Design and methods: A total of 622 people with newly diagnosed T2DM were selected as the study subjects, and 621 normoglycemic people were selected as control subjects. According to the diagnostic criteria of thyroid diseases, the subjects were divided into a normal thyroid function group and a subclinical hypothyroidism group. Both groups received a physical examination, and blood samples were collected. The measurement indexes included FPG, FINS, OGTT2hPG, OGTT2hINS, HbA1c, TC, TG, HDL-C, LDL-C, TSH, FT3 and FT4. HOMA-IR, HOMA-ß, and TFQI (thyroid feedback quantile index) were calculated. Results: There was no significant difference in age or sex distribution between the T2DM group and the normoglycemic group (P>0.05). The prevalence of thyroid dysfunction in the T2DM group was significantly higher than that in the normoglycemic group (16.39% vs. 11.27%, P<0.05), and among the different types of thyroid dysfunction, the prevalence of SCH was the highest at 14.95% (P<0.05). There was no significant difference in BMI, waist-hip ratio, blood lipid profile, HOMA-ß, and HOMA-IR values between the T2DM with subclinical hypothyroidism group (T2DM+SCH+ group) and the normal thyroid function group (T2DM+SCH- group) (P>0.05). The BMI, waist-hip ratio and HOMA-IR values of the normoglycemic group with subclinical hypothyroidism (T2DM-SCH+ group) were significantly higher than those of the normoglycemic group with normal thyroid function (T2DM-SCH- group) (P<0.05), and there were no significant differences between the T2DM+SCH- and T2DM+SCH+ groups (P>0.05). HOMA-ß values were significantly higher in the T2DM-SCH+ group than in the T2DM-SCH-, T2DM+SCH- and T2DM+SCH+ groups (P<0.05). As the TFQI value increased, the body weight, waist-hip ratio, diastolic blood pressure, FPG, OGTT2hPG and HbA1c values gradually increased in the T2DM group and normoglycemic group (P<0.05). HDL-C, FINS, OGTT2hINS and HOMA-ß values gradually decreased (P<0.05). Conclusion: Subclinical hypothyroidism only increases insulin resistance in normoglycemic people. As the sensitivity of the central thyroid decreases, the risk of developing diabetes increases.

The impact of global, regional, and national population ageing on disability-adjusted life years and deaths associated with diabetes during 1990-2019: A global decomposition analysis.

AIMS: To understanding the net regional, national, and economic effect of global population ageing on diabetes and its trends during 1990 and 2019 worldwide. METHODS: We employed a decomposition method to estimate the impact of population ageing on diabetes-related disability-adjusted life years (DALYs) and total deaths in 204 countries from 1990 to 2019 at the global, regional, and national level. This method separated the net effect of population ageing from population growth and changes in mortality. RESULTS: Globally, population ageing has become the major contributor to diabetes-related deaths since 2013. The increases in diabetes-related deaths attributed to population ageing exceeding the decreases in mortality change. Population ageing produced an additional 0.42 million diabetes-related deaths and 14.95 million DALYs from 1990 to 2019. At the regional level, population ageing is associated with the increases in diabetes-related deaths in 18 out of 22 regions. The highest increase in diabetes-related deaths attributed to population ageing occurred in men in East Asia (136.31%) and women in Central Latin America (118.58%). The proportion of diabetes-related deaths and DALYs attributable to population ageing showed a bell-shaped relationship with sociodemographic index (SDI) and peaked at high-middle-SDI countries. CONCLUSIONS: The decreases in diabetes-related deaths attributed to mortality change exceeded the increases attributed to population ageing between 1990 and 2019 globally and regionally. The diabetes-related deaths in high-middle-SDI countries were most impacted by population ageing.

Effects of TSH suppressive therapy on bone mineral density (BMD) and bone turnover markers (BTMs) in patients with differentiated thyroid cancer in Northeast China: a prospective controlled cohort study.

PURPOSE: This study aimed to evaluate the effects of thyroid-stimulating hormone (TSH) suppressive therapy on bone mineral density (BMD) and bone turnover markers (BTMs) in differentiated thyroid cancer (DTC) patients after postoperative 1-2 years in Northeast China. METHODS: Five male, sixteen premenopausal, and eight postmenopausal female DTC patients receiving TSH suppressive therapy after thyroidectomy were enrolled. Patients were matched with healthy controls in a ratio of 1:2. All participants completed postoperative 1-year follow-up, and postmenopausal women completed 2-year follow-up. We measured BMD of the lumbar spine (LS), femoral neck (FN), and total hip (TH) using dual-energy X-ray absorptiometry (DXA). Bone formation marker P1NP and bone resorption marker ß-CTX were also evaluated. Fracture risks were assessed by FRAX. RESULTS: There was no difference in BMD and BTMs between DTC patients and controls in the male group at 1-year follow-up. In the premenopausal women, the baseline P1NP was significantly lower in DTC patients than in the controls. The LS-BMD, FN-BMD, and TH-BMD in DTC patients were all higher than those in controls at 1-year follow-up. The difference in FN-BMD was not significant after adjusting for baseline P1NP. In the postmenopausal women, no differences in BMD and BTMs were observed between DTC patients and controls at the 1-year and 2-year follow-up. CONCLUSION: Our study indicated that postoperative 1-year TSH suppressive therapy did not show detrimental effects on BMD and BTMs in men, premenopausal, and postmenopausal DTC patients. The 2-year postoperative TSH suppressive therapy did not lead to additional loss of bone mass in postmenopausal DTC patients.

Factors Related to Metabolic Syndrome Development and Recovery in Chinese Adults: A Prospective Longitudinal Study.

Objective: This study was a prospective assessment of the epidemiological characteristics of metabolic syndrome (MetS) in cities in Northeast China. We explored the factors that affect the occurrence and outcome of MetS according to sex. Design and Methods: This was a longitudinal survey assessing MetS status among 750 urban community residents in China. At baseline, the intra-abdominal fat area was measured by MRI, simple anthropometric parameters (body mass index (BMI), waist circumference (WC), etc.) were used to evaluate fat distribution; blood pressure and blood lipid profile were measured; an oral glucose tolerance test (OGTT) was used to detect blood glucose; questionnaires were used to investigate lifestyles. Follow-up was conducted after 1.5 years (follow-up rate was 66.93%) to analyze the incidence of MetS and the influencing factors of MetS outcomes according to sex. Results: The 1.5-year cumulative incidence of MetS in the survey area was 25.40%. Men with visceral obesity were more likely to develop MetS than those with subcutaneous obesity (OR=9.778, p<0.05). Increased BMI (OR=1.379) and blood uric acid (BUA)>416 mmol/L (OR=2.318) were associated with the occurrence of MetS in men (all p<0.05). At the initial visit, BUA>356.9 mmol/L (OR=3.538), increased BMI (OR=1.212), and increased HbA1c (OR=2.577) were associated with the occurrence of MetS in women (all p<0.05). After 1.5 years, 25.37% of MetS patients no longer had MetS. Elevated diastolic blood pressure (DBP) (OR=1.097) and increased visceral fat (OR=1.023) at the initial visit made men with MetS less likely to recover from MetS (all p<0.05). Higher High-density lipoprotein cholesterol (HDL-C) at the initial visit made women with MetS more likely to recover from MetS (ß: -3.509, OR=0.003, p<0.05). Conclusion: There are different risk factors for MetS in different genders. Hyperuricemia is a risk factor for the onset of MetS in both men and women.

Combined Effects of Dyslipidemia and High Adiposity on the Estimated Glomerular Filtration Rate in a Middle-Aged Chinese Population.

BACKGROUND: Some studies have reported that chronic kidney disease (CKD) or the estimated glomerular filtration rate (eGFR) is significantly associated with metabolic abnormalities. METHODS: Six hundred forty-six community residents aged 45-60 years without overt renal dysfunction were recruited in this cross-sectional study. eGFR was estimated by serum creatinine measurement. The visceral fat area (VFA) and subcutaneous fat area (SFA) were assessed by magnetic resonance imaging (MRI). The body mass index (BMI) and waist-hip ratio (WHR) were also evaluated. Additionally, we tested the subjects' blood lipid levels to diagnose dyslipidemia. RESULTS: Compared with the subjects with neither dyslipidemia nor obesity, men with both dyslipidemia and high obesity indices, such as BMI, WHR and VFA, showed a significantly lower mean eGFR; women with dyslipidemia with high WHR, VFA or SFA also showed a significantly lower mean eGFR. Although an independent association between the metabolic variables and eGFR was not found except for BMI, some of the combined effects of each variable were related to eGFR decline. Comorbidity of dyslipidemia and high WHR was significant risk factor for eGFR reduction (ß -8.805, SD 4.116, p < 0.05). Additionally, comorbidity of dyslipidemia and high obesity indices such as BMI (ß -12.942, SD 5.268, p < 0.05) and VFA (ß -7.069, SD 3.394, p < 0.05) were significant risk factors for eGFR reduction in men. CONCLUSION: The combined effect of dyslipidemia and high obesity indices is significantly related to the decline in eGFR. The association is more profound in men.

The Type 2 Deiodinase Thr92Ala Polymorphism Is Associated with Higher Body Mass Index and Fasting Glucose Levels: A Systematic Review and Meta-Analysis.

BACKGROUND: Type 2 deiodinase (Dio2) is a selenoenzyme that is mainly expressed in the endoplasmic reticulum of the central nervous system, brown adipose tissue, and placenta and is responsible for outer ring deiodination of thyroxine (T4) to form biologically active triiodothyronine (T3). The Thr92Ala polymorphism of Dio2 has been found to be a potential risk factor for various diseases beyond the hypothalamus-pituitary-thyroid (HPT) axis. METHODS: We searched the relevant studies in the PubMed, Embase, and Cochrane Library databases and Google Scholar. A systematic review and meta-analysis of studies on the Thr92Ala polymorphism and metabolic parameters beyond the HPT axis (e.g., BMI, fasting glycemic traits, plasma lipid levels, and hypertension risk) were performed. RESULTS: Six eligible studies that analyzed the relationship between the Thr92Ala polymorphism and metabolic parameters beyond the thyroid were identified. All selected studies excluded patients with thyroid dysfunction, and diabetic patients were also excluded when fasting glucose and fasting insulin levels were meta-analyzed. The Thr92Ala polymorphism was found to be a significant risk factor for higher BMI (Std. mean difference 0.31 (0.01, 0.60), p = 0.04) and higher fasting glucose levels (Std. mean difference 1.18 (0.05, 2.31), p = 0.04). However, fasting insulin levels, plasma lipid levels, and hypertension risk showed a nonsignificant association with the Thr92Ala polymorphism. CONCLUSION: Compared with euthyroid noncarriers (Thr/Thr), euthyroid Ala92-Dio2 carriers showed increased BMI levels, and Ala92-Dio2 carriers also had higher fasting plasma glucose levels than matched euthyroid nondiabetic noncarriers.

Changes in the prevalence of obesity and hypertension and demographic risk factor profiles in China over 10 years: two national cross-sectional surveys.

BACKGROUND: Previous studies have shown increases in the prevalence of obesity and hypertension, but nationally representative data on recent changes in prevalence adjusted for population structure changes are lacking. Two nationwide surveys were conducted in 2007 and 2017 to assess the prevalence changes of these conditions in China. METHODS: A multistage stratified random sampling method was used to obtain a nationally representative sample of adults aged 20 years and older in mainland China in 2007 and 2017. Temporal changes in the prevalence of hypertension and obesity were investigated. Changes in blood pressure, body mass index (BMI) and waist circumference were also assessed. Logistic regression models were constructed to assess the changes in prevalence over time. FINDINGS: The weighted prevalence of hypertension (25.7% vs. 31.5%, P=0.04), high-normal blood pressure (11.7% vs. 14.3%, P<0.0001), general obesity (31.9% vs. 37.2%, P=0.008), and central obesity (25.9% vs. 35.4%, P=0.0002) was significantly higher in 2017 (n=72824) than in 2007 (n=45956) in the overall population. No significant changes in the prevalence of overweight and grade 1 or grade 2 hypertension were observed in the overall population, but a significantly higher prevalence was observed among participants aged 20-29 years for grade 1 hypertension (P=0.002) and among participants aged 70 years and older for grade 2 hypertension (P=0.046) in 2017. INTERPRETATION: Compared with 2007, the prevalence of hypertension and obesity was significantly higher among adults in mainland China after adjusting for demographic confounding factors in 2017. More targeted interventions and prevention strategies are needed to offset the increasing risk of cardiovascular disease due to increases in the prevalence of hypertension and obesity. FUNDING: The Clinical Research Fund of the Chinese Medical Association (Grant No. 15010010589), the National Natural Science Foundation of China (Grant No. 82000753), and the Chinese Medical Association Foundation and Chinese Diabetes Society (Grant No. 07020470055).

A Chinese survey on clinical practice in hyperthyroidism management: comparison with recent studies and guidelines.

OBJECTIVE: To conduct a questionnaire survey of the current clinical practice for overt hyperthyroidism in China. METHODS: An online questionnaire survey was conducted in July 2020. The two questionnaires covered 35 and 8 questions about non-pregnancy and pregnancy clinical practice for overt hyperthyroidism, respectively. RESULTS: One thousand, two hundred fifty-six physicians participated. Chief physicians and associate chief physicians accounted for 58.6% of the participants. Approximately 95.2% of the respondents chose the thyrotropin receptor antibody (TRAb) test to clarify the etiology of thyrotoxicosis, while only 27.0% of them chose radioactive iodine uptake (RAIU). In terms of treatment for non-pregnant patients, anti-thyroid drugs (ATDs) were the first choice, and most of the clinicians chose methimazole. Compared with clinicians in recent studies, Chinese physicians used serum TRAb to diagnose Graves' disease more commonly, and there were obviously more physicians preferring ATDs. For maternal hyperthyroidism, most physicians preferred propylthiouracil administration before or during the first trimester, which is consistent with the 2016 American Thyroid Association (ATA) guidelines. In terms of the initial ATD dose, monitoring the treatment process, indications for ATD withdrawal and treatment of special cases, the preferences of Chinese physicians were generally consistent with the guidelines. CONCLUSION: Chinese physicians can generally follow the ATA guidelines for the diagnosis and treatment of hyperthyroidism. Moreover, there are small differences from foreign studies or the guidelines with respect to particular problems. These findings provide evidence for future clinical research in China.

The Relationship Between Thyroid Function and Metabolic Syndrome and Its Components: A Cross-Sectional Study in a Chinese Population.

Objective: The present study examined the relationship between thyroid function status and the prevalence of metabolic syndrome in a Chinese population. Methods: Cross-sectional data were obtained from the Thyroid Disease, Iodine Nutrition and Diabetes Epidemiology (TIDE) Survey. A total of 62,408 subjects aged ≥18 years were enrolled. Differences in metabolic indicators and the prevalence of metabolic syndrome according to sex and thyroid function status were compared. Logistic regression was used to analyze the influence of thyroid function on metabolic syndrome and its components. Results: The prevalence of metabolic syndrome was generally higher in men than women. Overt hyperthyroidism and subclinical hypothyroidism had a significant effect on metabolism in men. Body mass index (BMI), waist circumference, and triglycerides (TGs) were significantly lower in men in the overt hyperthyroidism group, and BMI, waist circumference, systolic blood pressure (SBP) and TGs were higher in men in the subclinical hypothyroidism group than men in the normal group. Overt and subclinical hypothyroidism had significant impacts on metabolic components in women. BMI, waist circumference, TGs, SBP and DBP in the subclinical and overt hypothyroidism groups were significantly higher than the euthyroid group in women. The relative risk of abdominal obesity and hypertriglyceridemia was increased in women with hypothyroidism. Thyroid dysfunction had different effects on metabolic syndrome and its components before and after menopause. Conclusion: Thyroid function had important effects on the prevalence of metabolic syndrome. Women with hypothyroidism, especially post-menopausal women, had a higher risk of metabolic syndrome than men.

Kallmann Syndrome Due to Heterozygous Mutation in SOX10 Coexisting With Waardenburg Syndrome Type II: Case Report and Review of Literature.

Introduction: Kallmann syndrome (KS) is idiopathic hypogonadotropic hypogonadism with olfactory loss or decline. Waardenburg syndrome type II (WS2) is a clinically and genetically heterogeneous disease, characterized by congenital sensorineural deafness and abnormal pigmentation of the iris, hair, and skin. Recently, mutations in the well-known WS pathogenic gene SOX10 have been found in some KS patients with deafness, but whether SOX10 is a co-pathogenic gene of KS and WS remains uncertain. Here, we report a rare case of KS and WS2 co-occurrence due to SOX10 mutations. Methods: Detailed histories were collected through questionnaires and physical examination. Blood samples of the patient and his family members were collected after obtaining informed consents. Suspected mutations were amplified and verified by Sanger sequencing after the next generation sequencing of related genes. The raw sequence data were compared to the known gene sequence data in publicly available sequence data bases using Burrows-Wheeler Aligner software (BWA, 0.7.12-r1039). Results: A 28-year-old male patient sought treatment for hypogonadism and the absence of secondary sexual characteristics. In addition, he showed signs of obesity, hyposmia, sensorineural hearing loss, and blue iris. Magnetic resonance imaging (MRI) of the olfactory bulb showed small bilateral olfactory bulbs and tracts and diaphragma cerebri. MRI of the pituitary gland revealed a flat pituitary gland in the sella. Laboratory examination demonstrated hypogonadotropic hypogonadism, pituitary hypothyroidism, subclinical hypothyroidism, and the presence of insulin resistance with normal blood glucose levels. Sequencing of the SOX10 gene showed a 20 bp insertion in between coding bases 1,179 and 1,180 (c.1179_1180insACTATGGCTCAGCCTTCCCC). This results in a frame-shifting mutation of the 394th amino acid serine in exon4 with the resulting the amino acid sequence of the protein predicted to be TMAQPSP PSPAPSLTTL TISPQDPIMA TRARPLASTR PSPIWGPRSG PSTRPSLTPA PQGPSPTAPH TGSSQYIRHC PGPKGGPVAT TPRPAPAPSL CALFLAHLRP GGGSGGG*. Conclusion: SOX10 plays an important role in some critical stages of neural crest cell development and SOX10 mutation may be a common pathogenic factor for both KS and WS. Therefore, SOX10 mutation analysis should be considered for KS patients with combined WS clinical manifestations, especially deafness.

An Age-Specific Serum Thyrotropin Reference Range for the Diagnosis of Thyroid Diseases in Older Adults: A Cross-Sectional Survey in China.

Background: The fact that serum thyrotropin (TSH) levels increase with age may influence the diagnosis of thyroid diseases in older adults. This study aimed to establish an age-specific serum TSH reference range, examine the prevalence of thyroid diseases in older adults ≥65 years, and analyze the risk factors. Methods: A cross-sectional study of adult populations in 10 cities in China was conducted from 2010 to 2011. A total of 15,008 subjects were randomly selected and completed the present study. Urinary iodine concentration, serum TSH, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) titers were measured. Thyroid ultrasonography and questionnaires were completed by all the subjects. When the TSH level was abnormal, free thyroxine and/or free triiodothyronine levels were measured. Results: When the reference range of the general population was used, the prevalence rates of overt hypothyroidism (Ohypo) and subclinical hypothyroidism (Shypo) in older adults ≥65 years were significantly higher than those in younger adults <65 years (2.09% vs. 0.80% and 19.87% vs. 16.23%, respectively; p < 0.001). Positive TPOAb and positive TgAb were associated with the prevalence of Shypo in older adults. An age-specific serum TSH reference range was formulated according to guidelines set forth by the National Academy of Clinical Biochemistry. Both the median and upper limit values of serum TSH in older adults were higher than those in younger adults (2.58 [0.75-8.86] mIU/L vs. 2.38 [0.76-6.57] mIU/L; p < 0.001). Using the age-specific serum TSH reference range, the prevalence of Shypo in older adults was 3.3%, which was significantly lower than the prevalence based on the reference range of the general population (3.3% vs. 19.87%). The prevalence rates of Ohypo, overt hyperthyroidism (Ohyper), and subclinical hyperthyroidism (Shyper) did not change much (Ohypo: 1.6% vs. 2.09%; Ohyper: 0.7% vs. 0.52%; and Shyper: 3.8% vs. 0.73%). Positive TPOAb, but not positive TgAb, was also associated with the prevalence of Shypo as diagnosed with the age-specific serum TSH reference range. Conclusion: The serum TSH level increases with age, which may represent a normal compensatory phenomenon in older adults ≥65 years. To prevent misdiagnosis and mistreatment, the use of an age-specific serum TSH reference range is recommended in older adults for the diagnosis of thyroid diseases.

Thyrotropin Regulates eNOS Expression in the Endothelium by PGRN Through Akt Pathway.

To investigate the expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) in the aorta of subclinical hypothyroidism (SCH) rat model. The mechanisms underlying thyrotropin (TSH) affecting eNOS and PGRN expression in human umbilical vein endothelial cells (HUVECs) cultured in vitro were investigated. In the current study, SCH rat models were established by the administration of L-T4 injection after thyroidectomy in Wistar rats, as opposed to that in the normal and clinical hypothyroidism (CH) groups. The concentrations of NO (pmol/µL) in the SCH and CH groups were significantly lower than that in the normal group (40.8 ± 7.6 and 32.9 ± 10.8 vs. 51.2 ± 12.1, P < 0.05). However, the expression level of eNOS is increased significantly (P < 0.05) in both SCH and CH groups; a similar result was observed for the PGRN protein. In cultured HUVECs, TSH can also up-regulate the expression of eNOS; however, it is accompanied by a reduced concentration of NO and increased level of superoxide anion, thereby indicating uncoupled eNOS. As eNOS is increased, we found that Akt in HUVECs were upregulated by TSH, as well as PGRN expression. While inhibiting the expression of PGRN in HUVECs using siRNA, the expression of eNOS, as well as Akt were also inhibited. In conclusion, SCH can induce vascular endothelial dysfunction in rats, and PGRN participated in the process of TSH-induced expression of Akt/eNOS in the endothelium.

Effects of circulating member B of the family with sequence similarity 3 on the risk of developing metabolic syndrome and its components: A 5-year prospective study.

AIMS/INTRODUCTION: Member B of the family with sequence similarity 3 (FAM3B), also known as pancreatic-derived factor, is mainly synthesized and secreted by islet ß-cells, and plays a role in abnormal metabolism of glucose and lipids. However, the prospective association of FAM3B with metabolic disorders remains unclear. The present study aimed to reveal the predictive relationship between pancreas-specific cytokine and metabolic syndrome (MetS). MATERIALS AND METHODS: A total of 210 adults (88 men and 122 women) without MetS, aged between 40 and 65 years, were recruited and received a comprehensive health examination. Baseline serum FAM3B levels were determined by sandwich enzyme-linked immunosorbent assay. Subsequently, all participants underwent a follow-up examination after 5 years. MetS was identified in accordance with the International Diabetes Federation criteria. RESULTS: During follow up, 35.7% participants developed MetS. In comparison with the non-MetS group, participants with MetS had an increased serum FAM3B at baseline (21.85 ng/mL [19.38, 24.17 ng/mL] vs 28.56 ng/mL [25.32, 38.10 ng/mL], P < 0.001). Moreover, serum FAM3B was significantly associated with variations in fasting plasma insulin (r = -0.306, P < 0.001), homeostasis model assessment of ß-cell function (r = -0.328, P < 0.001) and homeostasis model assessment of insulin resistance (r = -0.191, P = 0.006). Furthermore, a positive correlation between baseline FAM3B and the incidence of MetS was observed, even after multivariable adjustment (relative risk 1.23 [1.15, 1.31], P < 0.001). Furthermore, the optimal cut-off values of FAM3B was 23.98 ng/mL for predicting MetS based on the Youden Index. CONCLUSIONS: Elevated circulating FAM3B might be considered as a predictor of newly-onset MetS and its progression.

Comparison of anthropometric indices for predicting the risk of metabolic syndrome and its components in Chinese adults: a prospective, longitudinal study.

OBJECTIVES: Our study aimed to distinguish the ability of anthropometric indices to assess the risk of metabolic syndrome (MetS). DESIGN: Prospective cohort study. SETTING: Shenyang, China. PARTICIPANTS: A total of 379 residents aged between 40 and 65 were enrolled. 253 of them were free of MetS and had been followed up for 4.5 years. METHODS: At baseline, all the participants underwent a thorough medical examination. A variety of anthropometric parameters were measured and calculated, including waist circumference (WC), body mass index (BMI), a body shape index (ABSI), abdominal volume index (AVI), body adiposity index, body roundness index, conicity index, waist-to-hip ratio and visceral adiposity index (VAI). After 4.5 year follow-up, we re-examined whether participants were suffering from MetS. A receiver operating characteristic (ROC) curve was applied to examine the potential of the above indices to identify the status and risk of MetS. OUTCOMES: Occurrence of MetS. RESULTS: At baseline, 33.2% participants suffered from MetS. All of the anthropometric indices showed clinical significance, and VAI was superior to the other indices as it was found to have the largest area under the ROC curve. After a 4.5 year follow-up, 37.8% of men and 23.9% of women developed MetS. ROC curve analysis suggested that baseline BMI was the strongest predictor of MetS for men (0.77 (0.68-0.85)), and AVI was the strongest for women (0.72 (0.64-0.79)). However, no significant difference was observed between WC and both indices. In contrast, the baseline ABSI did not predict MetS in both genders. CONCLUSIONS: The present study indicated that these different indices derived from anthropometric parameters have different discriminatory abilities for MetS. Although WC did not have the largest area under the ROC curve for diagnosing and predicting MetS, it may remain a better index of MetS status and risk because of its simplicity and wide use.

Food Addiction in Patients with Newly Diagnosed Type 2 Diabetes in Northeast China.

AIM: The aim of the study was to explore the prevalence of food addiction (FA) in individuals with newly diagnosed type 2 diabetes mellitus (T2DM) in China and to analyze risk factors of FA. METHODS: A total of 624 subjects [312 individuals with newly diagnosed T2DM, 312 age-matched and body mass index (BMI)-matched healthy participants] were recruited. All participants were asked to complete the Yale Food Addiction Scale (YFAS) and received physical and lab examinations. The T2DM group was further divided into a FA group and a non-FA group. RESULTS: Of the patients with newly diagnosed T2DM, 8.6% (27/312) met the FA diagnostic criteria proposed by the YFAS (7.6% in men and 10.1% in women, P = 0.43), while 1.3% (4/312) met the criteria in the control group. Logistic regression analysis showed that FA in the T2DM group was positively related to BMI and negatively related to age. T2DM with FA had a significantly higher uric acid (UA). CONCLUSION: Both men and women with newly diagnosed T2DM, especially in northeast China, were more likely to suffer from FA. T2DM patients with FA were younger and had higher UA.

The correlation between serum free thyroxine and regression of dyslipidemia in adult males: A 4.5-year prospective study.

Elevated free thyroxine (FT4) levels may play a protective role in development of dyslipidemia. However, few prospective studies have been performed to definite the effects of thyroid hormones on the improvement of dyslipidemia and its components. Thus, this study aims to clarify the association between thyroid hormones within normal range and reversal of dyslipidemia in the absence of intervention.A prospective analysis including 134 adult males was performed between 2010 and 2014. Anthropometric parameters, thyroid function, and lipid profile were measured at baseline and during follow-up. Logistic regression and receiver operating characteristic (ROC) analysis were conducted to identify the variables in forecasting the reversal of dyslipidemia and its components.During 4.5-year follow-up, 36.6% (49/134) patients resolved their dyslipidemia status without drug intervention. Compared with the continuous dyslipidemia group, subjects in reversal group had elevated FT4 and high-density lipoprotein cholesterol (HDL-C) levels, as well as decreased total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels at baseline. Furthermore, baseline FT4 is negatively associated with the change percentages of TG (r = -0.286, P = .001), while positively associated with HDL-C (r = 0.227, P = .008). However, no correlation of lipid profile change percentages with FT3 and TSH were observed. Furthermore, the improving effects of baseline FT4 on dyslipidemia, high TG, and low HDL-C status were still observed after multivariable adjustment. In ROC analysis, areas under curve (AUCs) for FT4 in predicting the reversal of dyslipidemia, high TG, and low HDL-C were 0.666, 0.643, and 0.702, respectively (P = .001 for dyslipidemia, .018 for high TG, and .001 for low HDL-C).Higher FT4 value within normal range may ameliorate the dyslipidemia, especially high TG and low HDL-C status, in males without drug intervention. This suggests that a more flexible lipid-lowering therapy may be appropriate for patients with high-normal FT4.