Visfatin and Retinol Binding Protein-4 in Young-Onset Type 2 Diabetes Mellitus.

Background and Objectives: The prevalence of type 2 diabetes mellitus in adolescents has increased rapidly in recent decades. However, the role of adipokines on pathophysiology in young-onset type 2 diabetes mellitus (YDM) is not clear. In this article, we explored the relationships between the adipokines (visfatin and retinol binding protein 4 (RBP4)) and metabolic syndrome (MetS) components in both YDM and late-onset type 2 diabetes mellitus (ODM). Materials and Methods: There were 36 patients with YDM (23.6 ± 4.8 years) and 36 patients with ODM (54.3 ± 10.1 years) enrolled. Visfatin, RBP4, and MetS components were measured. The relationships between visfatin, RBP4 and MetS components were assessed in YDM and ODM. Results: The visfatin, but not the RPB4 level, was significantly higher in YDM than in ODM. After adjusting for age and body mass index, visfatin was not related to any MetS components except that there was a negative correlation with fasting plasma glucose (FPG). As for RPB4, triglyceride was found to be positively and FPG negatively related to RBP4 in YDM. However, in ODM, the only positive relationship that existed was between RBP4 and diastolic blood pressure. Conclusions: In conclusion, both visfatin and RBP4 had certain roles in diabetes and MetS although their relationships were different in YDM and ODM. Further studies are needed to explore their physiological and pathological effects in glucose metabolism.

Serum interferon levels associated with the disease activity in women with overt Graves' disease.

BACKGROUND: Inflammatory cytokines participate in immune reactions and the pathogenesis of autoimmunity. Herein, we quantified four groups of inflammatory cytokines, including interferons (IFNs), the tumor necrosis factor (TNF) superfamily (TNFSF), interleukin (IL)-related cytokines, and bone and extracellular matrix remodeling-related cytokines to determine their contributions in women with overt Graves' disease (GD). METHODS: Forty-three women with GD were enrolled in this cross-sectional study. Thirty-seven cytokines, thyroid-stimulating hormone (TSH), free thyroxine, and TSH receptor antibody (TSHRAb) were quantified. GD patients with a low TSH level at the time of sample collection were defined as having active GD. RESULTS: Patients with active GD had higher IFN-α2, IFN-γ, IFN-λ1, and IFN-λ2 levels than those with inactive GD. In addition, certain TNFSF cytokines, including soluble cluster of differentiation 30 (sCD30), TNFSF member 14 (TNFSF14), pentraxin (PTX)-3, soluble TNF receptor 2 (sTNF-R2), and thymic stromal lymphopoietin (TSLP) were higher in active GD than in inactive GD. Moreover, active GD patients had higher IL-2, IL-12(p40), osteocalcin (OCN), and matrix metalloproteinase (MMP)-3 than inactive GD patients. All IFNs except IFN-λ1 were correlated with TSHRAb titers. Moreover, TNFSF cytokines, consisting of B-cell-activating factor, sCD30, TNFSF14, PTX-3, sTNF-R2, and TSLP, were associated with TSHRAb levels. CONCLUSIONS: Serum IFNs could be the most remarkable cytokines in modulating the disease severity and TSHRAb titers in women with full-blown GD. Further molecular-based research to clarify the actual role of IFNs in the disease progression of GD is needed.

Predictors of abnormality in thallium myocardial perfusion scans for type 2 diabetes.

Type 2 diabetes mellitus (T2DM) increases coronary artery disease (CAD) risk. In this study, we used T2DM clinical variables to predict abnormality in thallium-201 myocardial perfusion scans (Th-201 scans). These clinical variables were summed stress score (SSS), summed rest score, and summed difference score (SDS), with data obtained from 368 male and 428 female participants with T2DM. Multiple linear regression results were as follows. In male participants, body mass index (BMI) and creatinine (Cr) were associated with SSS (ß = 0.224, p < 0.001; ß = 0.140, p = 0.022, respectively), and only BMI was associated with SDS (ß = 0.174, p = 0.004). In female participants, BMI and high-density lipoprotein cholesterol level were associated with SSS (ß = 0.240, p < 0.001; ß = - 0.120, p = 0.048, respectively), and only BMI was correlated with SDS (ß = 0.123, p = 0.031). Our multivariate logistic regression indicated that in male and female participants, BMI was the only independent indicator of high SSS (SSS ≥ 9). In this study, we demonstrated that male patients have a higher SSS and SDS than female patients do in Th-201 scans for T2DM in a Chinese population. For male and female patients, BMI was the strongest predictor of abnormality in Th-201 scans. Our results can help clinicians identify patients with T2DM at high risk of CAD.

Associations of gene polymorphisms in interferon-alpha signature-related genes with autoimmune thyroid diseases.

Interferon (IFN)-α treatment predisposes patients to the occurrence of autoimmune thyroid disease (AITD). METHODS: We investigated associations of single nucleotide polymorphisms (SNPs) of molecules participating in the IFN-α signature, including rs2304204 and rs2304206 of IFN regulatory factor 3 (IRF3), rs1061501 of IRF7, and rs7708392 of TNFA1P3-interacting protein 1 with serum IFN-α levels and AITD in an ethnic Chinese (ie Taiwanese) population. Totally, 319 patients with Graves' disease (GD), 83 patients with Hashimoto's thyroiditis (HT) and 351 healthy controls were recruited. RESULTS: There were increased percentages of the C allele, and CC and TC + CC genotypes of rs1061501 in GD patients compared to the controls. HT patients had higher serum IFN-α levels compared to the controls, while there was no difference in serum IFN-α levels between patients with GD and controls. However, patients with GD in a remission status had lower serum IFN-α levels than those without remission. On the other hand, the C allele of rs1061501 was only associated with serum IFN-α levels in patients with HT. CONCLUSIONS: The SNP rs1061501 of IRF7 was associated with the development of GD. Serum IFN-α levels were associated with HT, while they might modify the disease status of GD. Moreover, a genetic effect of rs1061501 on regulating serum IFN-α production was observed in HT.

Synchronized expressions of serum osteopontin and B cell-activating factor in autoimmune thyroid disease.

BACKGROUND: Osteopontin (OPN) is recognized as a potent immunoregulator of autoimmune disease. In the study, we tried to explore the association of serum OPN levels with autoimmune thyroid disease, including Graves' disease (GD) and Hashimoto's thyroiditis (HT), in an ethnic Chinese population. MATERIALS AND METHODS: We enrolled 131 patients with GD, 33 patients with HT and 123 healthy controls. Serum OPN, B cell-activating factor (BAFF) and interferon (IFN)-α levels were quantified. Graves' disease patients with high thyroid function at the time of sample collection were defined as having active GD, while the other patients were defined as having inactive GD. RESULTS: Serum OPN levels were higher in active GD than in inactive GD and the control groups (P = 0.001 and P = 0.018, respectively). In GD, significant associations of OPN levels with thyroid-stimulating hormone receptor antibody (TSHRAb) levels were observed in women (r = -0.344, P = 0.002, and r = 0.440, P = 0.004, respectively) but not in men. Osteopontin levels were associated with BAFF levels only in women with GD or HT (r = 0.506, P < 0.001 and r = 0.430, P = 0.025, respectively), but not in men with GD or HT. CONCLUSIONS: Serum OPN levels were upregulated in active GD, and serum OPN levels were associated with thyroid function and TSHRAb levels in GD. Additionally, OPN levels were correlated with BAFF levels in GD and HT. The associations of OPN levels with clinical phenotypes of GD and BAFF levels showed a dimorphic pattern.

Associations of secreted phosphoprotein 1 and B lymphocyte kinase gene polymorphisms with autoimmune thyroid disease.

BACKGROUND: Dysregulation of the type 1 interferon (IFN)-related signalling pathway predisposes one to autoimmune diseases. Possible associations of single-nucleotide polymorphisms (SNPs) of secreted phosphoprotein 1 (SPP1) and B lymphocyte kinase (BLK) of the type 1 IFN-related signalling pathway with autoimmune thyroid disease (AITD) in an ethnic Chinese (ie Taiwanese) population were tested. METHODS: Totally, 83 Hashimoto's thyroiditis (HT) patients, 319 Graves' disease (GD) patients and 369 controls were enrolled. Genotypes of the two SNPs (rs1126772 and rs1126616) of SPP1 and two SNPs (rs13277113 and rs2736340) of BLK were determined. RESULTS: Our results showed reduced percentages of the G allele of rs13277113 of BLK in GD (P = 0.037, odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.62-0.99) and HT (P = 0.002, OR = 0.54, 95% CI = 0.36-0.81), compared to the controls. At the same time, lower frequencies of the C allele of rs2736340 of BLK in GD (P = 0.025, OR = 0.76, 95% CI = 0.60-0.97) and HT (P = 0.003, OR = 0.53, 95% CI = 0.35-0.81) than the controls were also observed. There were significantly higher AT haplotype frequencies of rs1327713 and rs2736340 in GD and HT patients than in the controls (P = 0.025, OR = 1.31, 95% CI = 1.03-1.67, and P = 0.003, OR = 1.89, 95% CI = 1.24-2.87, respectively). Moreover, the anti-microsomal antibody titre was associated with rs2736340. CONCLUSIONS: Genetic variants of rs13277113 and rs2736340 of BLK were associated with susceptibility to GD, HT and AITD in an ethnic Chinese population. Our results suggest the BLK may participate in the pathogenesis of GD, HT and AITD.

Iodine status of adults in Taiwan 2005-2008, 5 years after the cessation of mandatory salt iodization.

BACKGROUND/PURPOSE: Iodine deficiency causes a broad spectrum of disorders across all ages. Mandatory salt iodization in Taiwan successfully reduced the goiter rate from 21.6% to 4.3% in schoolchildren surveyed in 1971. The program continued until 2003 when salt iodization was changed from mandatory to voluntary. The purpose of this study was to investigate the iodine status of Taiwanese individuals after the change in the iodine policy. METHODS: Urinary iodine (UI) was measured in samples from adults in the Nutrition and Health Survey in Taiwan 2005-2008. RESULTS: The median UI level was 100 µg/L, and the percentage of populations with UI levels below 100 µg/L and 50 µg/L was 50.1% and 15.1%, respectively, indicating that the iodine status was borderline adequate. Men had a higher UI level than women (102 µg/L vs. 98 µg/L, p = 0.003), and older individuals (age > 60 years) had a lower UI level than younger people, particularly in women. The iodine status of the population < 50 years was sufficient, but it was insufficient in older groups. Mild iodine insufficiency was noted in all areas of Taiwan except the Southern area and Penghu islands, with the lowest UI level of 79 µg/L in the Mountain area. Although the UI level of women of childbearing age (19-44 years) was 103 µg/L, there may be a risk of iodine deficiency during pregnancy. CONCLUSION: The iodine nutrition of the Taiwanese population in 2005-2008 was borderline adequate, with insufficiency in some subgroups. Further monitoring of the iodine status is necessary.

Association of IRF8 gene polymorphisms with autoimmune thyroid disease.

BACKGROUND: The occurrence of autoimmune thyroid disease (AITD) is known to have a major adverse effect on interferon (INF)-α treatment. The genetic variant of the INF regulatory factor 8 (IRF8), a type 1 INF regulator, is associated with susceptibility to systemic lupus erythematosus and multiple sclerosis. In this study, we investigated possible associations of the IRF8 polymorphisms, rs17445836 and rs2280381, with AITD in an ethnic Chinese population. MATERIAL AND METHODS: In total, 278 patients with Graves' disease (GD) and 55 patients with Hashimoto's thyroiditis (HT), and 252 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing were used for genotyping. RESULTS: Significantly lower frequencies of the GA genotype and A allele of rs17445836 were found in the HT group than in the control group (P = 0·028, odds ratio (OR) = 4·71 and P = 0·022, OR = 4·40, respectively). Both rs17445836 and rs2280381 were associated with the presence of an antimicrosomal antibody (AmiA), and rs2280381 was also associated with the presence of an antithyroglobulin antibody (ATA) in AITD. Moreover, rs17445836 was associated with the level of AmiA in AITD. CONCLUSIONS: rs17445836 of IRF8 is a possible genetic variant associated with the development of HT. rs17445836 was associated with the production of thyroid antibody, and the GG genotype of rs17445836 was associated with a higher AmiA titre than the GA genotype.

Mean arterial pressure is better at predicting future metabolic syndrome in the normotensive elderly: a prospective cohort study in Taiwan.

OBJECTIVE: To compare four different blood pressure (BP) measurements-systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP)-in predicting future metabolic syndrome (MetS) among the normotensive elderly population, and to estimate the optimal cutoff value of the best single measurement for clinical practice. METHODS: A total of 2782 non-medicated participants aged ≥ 60 years were enrolled in a standard health examination program in Taiwan from January 2004 to December 2013. Two thirds of the participants were randomly designated as the training group (n=1855) and the other one third as the validation group (n=927). The mean follow-up time was 3.60 years for both the training and validation groups. MAP and PP were calculated from SBP and DBP. RESULTS: SBP, DBP, and MAP were associated with future MetS, whereas PP was not. MAP had the largest hazard ratio in Cox regression (men 1.342 [95% CI 1.158-1.555] and women 1.348 [95% CI 1.185-1.534] in the training group; men 1.640 [95% CI 1.317-2.041] and women 1.485 [95% CI 1.230-1.794] in the validation group) and the largest area under the receiver operating characteristic curve (men 0.598 ± 0.021 and women 0.602 ± 0.021 in the training group). Multivariable Cox regression further indicated that a higher MAP level was independently associated with the future occurrence of MetS. Participants with MAP above the cutoff value (84.0mm Hg for men, 83.3mm Hg for women) had a higher cumulative incidence of MetS than did their counterparts after four years' follow-up in both the training and validation groups. The results derived from the training data could be replicated in the validation data, indicating that the results were generalizable across distinct samples. CONCLUSIONS: MAP is more accurate than SBP, DBP, and PP in predicting future MetS among the normotensive geriatric population. Calculation of MAP is recommended when dealing with normotensive patients aged ≥ 60 years in clinical practice.

Using hematogram model to predict future metabolic syndrome in elderly: a 4-year longitudinal study.

OBJECTIVES: The metabolic syndrome (MetS) is proposed to predict future occurrence of cardiovascular diseases and diabetes. There are some other "non-traditional" risk factors such as hematogram components that are also related to the same endpoints as MetS. In this four-year longitudinal study, we used hematogram components to build models for predicting future occurrence of MetS in older men and women separately. METHODS: Subjects above 65 years without MetS and related diseases were enrolled. All subjects were followed up until they developed MetS or until up to four years from the day of entry, whichever was earlier. RESULTS: Among the 4539 study participants, 1327 developed MetS. Models were built for men and women separately and the areas under the receiver operation curves were significant. The Kaplan-Meier plot showed that the models could predict future MetS. Finally, Cox regression analysis showed that the hematogram model was correlated to future MetS with hazard ratios of 1.567 and 1.738 in men and women, respectively. CONCLUSION: Our hematogram models could significantly predict future MetS in elderly and might be more practical and convenient for daily clinical practice.

Use of white blood cell counts to predict metabolic syndrome in the elderly: a 4 year longitudinal study.

BACKGROUND: The white blood cell (WBC) count was one of the first inflammatory markers associated with metabolic syndrome (MetS). Recently, two longitudinal studies have demonstrated a cause and effect relationship between MetS and WBC counts among middle-aged adults. However, no study has used WBC cutoff values to predict MetS in the elderly. METHODS: Subjects who underwent routine health checkups, and were above 60 years of age, were enrolled. All subjects were followed-up until they developed MetS or until 4 years from the date of entry, whichever came earlier. Of the 4539 subjects eligible for enrollment, 3428 subjects comprised the study group and 1111 subjects comprised the validation group. RESULTS: WBC counts were significantly different between subjects with and without MetS in both genders. Using the ROC curve, WBC cutoff values of 5.7 × 10(3)/µl in males and 5.0 × 10(3)/µl in females were associated with the increased risk of developing MetS (all p values <0.001). Using these WBC cutoff values, the hazard ratio (HR) for females was significant in both the study group and validation group. However, the HR for males failed significance in the validation group. Kaplan-Meier plots and κ coefficients confirmed that the WBC cutoff value could predict development of MetS in women but not in men. CONCLUSIONS: The association between WBC count and MetS was gender specific. A WBC cutoff value greater than 5.0 10(3)/µl may predict the development of MetS in elderly women.

The effect of chromium on inflammatory markers, 1st and 2nd phase insulin secretion in type 2 diabetes.

OBJECTIVE: Impaired insulin sensitivity (SI) and ß-cell function are the two main causes of type 2 diabetes (T2D) and are related to low-grade inflammation status. Trivalent chromium has shown to improve SI in our previous study. This might be due to the ability of decreasing interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) shown in animal studies. In the current study, we measured SI, ß-cell function, and plasma levels of IL-6 and TNF-α after treatment of chromium chloride (GaCr) in T2D. RESEARCH DESIGN AND METHODS: Sixty-six patients were randomly assigned to the 20 g of GaCr milk powder studying group or the milk powder placebo group. Oral glucose tolerance test was performed before and after the treatment. The SI and the ß-cell function were measured as well. RESULTS: The SI was significantly improved. At the same time, the static insulin responsivity index (Φs) was significantly higher after the treatment (p = 0.003). On the other hand, the dynamic insulin responsivity index (Φd) remained unchanged. Interestingly, a significant decrease in the IL-6 level after the treatment (p = 0.015) was noted. Although there was a trend of decreasing in TNF-α, it was not statistically significant. Finally, there was no significant correlation between the δ-IL-6, SI, and Φd after GaCr treatment. CONCLUSIONS: In conclusion, other than the improvement of SI, GaCr could also improve the second phase of insulin responsivity (Φs) and IL-6. However, δ-IL-6 was correlated with neither δ-SI nor δ-Φs which indicated that the improvement of SI and Φs might involve mechanisms other than lower inflammatory effect.

Predicting metabolic syndrome by using hematogram models in elderly women.

BACKGROUND: Low-grade inflammatory status was thought to be a major underlying mechanism in MetS. White blood cell (WBC) count was one of the inflammatory markers identified to be associated with MetS. Moreover, not only WBC but also hemoglobin (Hb) and platelet (PLT) were all associated with MetS. OBJECTIVE: In this study, we tried to build models by the hematogram components. In this way, we can not only predict the occurrence of MetS with a relatively low-cost and routine lab test, but also can understand more about the relationships between low grade inflammation and MetS. METHODS: We randomly collected subjects over 65 years old from MJ Health Screening Center's database between 1999 and 2008. After excluding subjects with medications for hypertension, hyperlipidemia and/or diabetes, 13,132 female were eligible for analysis. RESULTS: All the MetS components, hematogram parameters and age were higher in group with MetS. In the correlation matrix, all these three hematogram parameters (WBC, Hb and PLT) were correlated with MetS components except for the correlation between Hb and HDL-C. The ROC curves showed that the model 3 (PLT + Hb + WBC) had greatest area under the curve of 0.631 with the sensitivity of 58.1% and specificity of 61.4%. CONCLUSIONS: Our findings have shown that all the three hematogram parameters are related to MetS. The results not only shed light on the complex relationships, but also demonstrate a common and easy model to aid clinicians to be more aware of the occurrence of MetS.

Estimation of the disposition index based on components of metabolic syndrome.

Decreased insulin sensitivity (IS) and impaired insulin secretion are major pathological features of type 2 diabetes (T2DM). The product of these factors is the disposition index (DI). We aimed to develop an equation for predicting DI. We enrolled 167 participants in our study. We randomly assigned 126 (75%) of the participants to the study group, whose data would be used to build the equation for estimating the DI. The remaining 41 participants comprised the external validation group. A frequently sampled intravenous glucose-tolerance test was performed for all participants, and the IS, the glucose sensitivity, the acute insulin response to the glucose load, and the DI were determined. Three factors were selected from multiple linear regression analysis, and we constructed the equation log (DI) = 2.449 - 0.113 × fasting plasma glucose + 0.046 × body mass index - 0.612 × high-density lipoprotein cholesterol. Using this equation, the calculated log (DI) significantly correlated with the measured log (DI) in the external validation group (r = 0.428, p = 0.007). By using the equation based on the demographic data and measurements of metabolic syndrome components, the DI could be predicted with acceptable accuracy (r = 0.428). Because of the relationships between the MetS and demographic parameters, this method of predicting DI may help further clinicians' understanding of the underlying pathological mechanisms in T2DM.

High Fatty Acid-Binding Protein 4 Expression Associated with Favorable Clinical Characteristics and Prognosis in Papillary Thyroid Carcinoma.

Fatty acid-binding protein 4 (FABP4), a fatty acid transporter that coordinates lipid metabolism, is reported to exert a tumorigenic role in certain cancers. We investigated the effects of FABP4 in the carcinogenesis of thyroid cancer. Bioinformatics data about FABP4 in thyroid cancer were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Sixteen paired papillary thyroid cancer (PTC) tissues from Taipei Medical University (TMU) were gathered, and commercial thyroid cancer complementary (c)DNA and tissue arrays were purchased to measure FABP4 messenger (m)RNA and protein levels. By analyzing data from the GEO and TCGA, we showed that FABP4 mRNA was reduced in PTC and follicular thyroid carcinoma (FTC). In addition, a lower FABP4 mRNA level in PTC was associated with poor clinical parameters and outcomes in the TCGA database. Moreover, FABP4 transcripts and proteins were downregulated in PTC and FTC, and its mRNA expression was associated with PTC staging in clinical specimens. In the TCGA database and TMU cohort, FABP4 mRNA levels were associated with thyroglobulin (r = 0.511 and r = 0.656, respectively), thyroid peroxidase (r = 0.612 and r = 0.909, respectively), and sodium iodide symporter (r = 0.485 and r = 0.637, respectively) transcripts. In conclusion, FABP4 mRNA and protein levels were reduced in PTC and FTC, and may be used as a potential indicator for thyroid cancer evolution in clinical settings. Further, well-designed research to dissect the molecular mechanism of FABP4 in modulating thyroid carcinogenesis is needed.

Evaluation of second phase insulin secretion with simple surrogates derived from the mixed meal tolerance test in patients with type 2 diabetes.

The major contributors to the pathogenesis of type 2 diabetes are impaired insulin action and insulin secretion, including second phase insulin secretion (2nd ISEC). This study aimed to compare surrogates derived from the mixed meal tolerance test (MTT) with 2nd ISEC derived from modified low-dose graded glucose infusion (M-LDGGI) in patients with type 2 diabetes. We were subsequently able to decide which surrogate would be performed easily and accurately. Twenty type 2 diabetes patients were enrolled. They received both MTT and M-LDGGI. The standardized MTT meals were provided at 8:00 A.M. and 12:00 P.M. The M-LDGGI was a simplified version of the Polonsky method; only two 80-min stages of glucose infusion (2 and 6 mg/kg/min) were given. The slopes of the insulin to glucose curve during the test were regarded as the 2nd ISEC. First, we used the area under the insulin curve (AUC(IN)) during MTT to quantify the 2nd ISEC. The best correlated AUC(IN) was from 60-240 min. Second, the slopes between any two time points of the plasma insulin to glucose level (SLOPE(I/G)) were also assessed. The time period best correlated with 2nd ISEC was from 0-120 min (SLOPE0₋120). Finally, the insulin-to-glucose ratio (IGr) of each time point was used to estimate the 2nd ISEC, and the best correlation was observed at 180 min. In conclusion, estimating 2nd ISEC surrogates derived from MTT proved to be possible. The most accurate surrogate is the SLOPE0₋120, while IG(r180) is another less precise but more convenient method.

Associations of serum keratin 1 with thyroid function and immunity in Graves' disease.

BACKGROUND: Autoimmune thyroid disease (AITD) can cause enormous health burdens; however, trustworthy biomarkers in identifying the onset and progression of AITD are limited. In this study, we attempted to discover new potential serum biomarkers to discriminate AITD using mass spectrometry (MS). METHODS: In the biomarker study cohort, 20 patients with Graves' disease (GD), 20 patients with Hashimoto's thyroiditis (HT), and 20 healthy controls were enrolled for a liquid chromatographic-tandem MS assessment. A novel biomarker, keratin 1 (KRT1), was selected for further evaluation in the validation cohort, including 125 patients with GD, 34 patients with HT, and 77 controls. Relationships of serum KRT1 with AITD-related immunomodulatory cytokines were also analyzed using enzyme-linked immunosorbent assays (ELISAs). RESULTS: In the MS analysis, KRT1 was the single marker overexpressed in GD, while it was underexpressed in HT. In the ELISA analysis of the validation cohort, KRT1 was consistently upregulated in GD, while it was not downregulated in HT. There were significant associations of KRT1 levels with thyroid function in GD, AITD, and overall subjects. Additionally, a significant association of KRT1 levels with thyroid-stimulating hormone receptor antibody (TSHRAb) levels was observed. Moreover, there were significant associations of KRT1 with osteopontin (OPN) and B-cell activating factor (BAFF) levels in GD. CONCLUSIONS: Serum KRT1 levels were upregulated in GD and were associated with thyroid function and TSHRAb levels. Moreover, KRT1 was correlated with the BAFF and OPN levels in GD patients. Further molecular-based research to elucidate the role of KRT1 in the pathogenesis of AITD is needed.

The pathogenic role of IFN-α in thyroiditis mouse models.

AIM: Patients with chronic hepatitis C are frequently treated with interferon (IFN)-α. Autoimmune thyroid disease occurs in 20% ~ 40% of IFN-α-treated patients. In this study, the effects of IFN-α administration on triggering and regulating autoimmune thyroiditis in various animal models were evaluated. MAIN METHODS: Exogenous IFN-α was given to naive CBA mice, and both thyroglobulin (TG) immunization-induced (CBA) and spontaneous autoimmune thyroiditis (NOD·H-2 h4) models. Thyroid function, and anti-thyroglobulin antibody (ATA) and B-cell-activating factor (BAFF) levels were measured. Alterations in transcriptome profiles were analyzed. KEY FINDINGS: In the TG-induced thyroiditis model, IFN-α administration reduced plasma free thyroxine levels but did not alter ATA titers, BAFF levels, or the severity of histological changes. Interestingly, even without changes in thyroid functions, four of eight mice in the IFN-α alone group exhibited thyroiditis compared to the control group. Immunologically, mice in the IFN-α group exhibited profound CD3+ cell infiltration in the thyroid and higher plasma BAFF levels compared to the control group. Meanwhile, pathological and serological alterations after IFN-α administration were not observed in the NOD·H-2 h4 model. An RNA sequencing analysis revealed that immunoregulatory signatures were not excited by IFN-α treatment in naive CBA mice. Meanwhile, innate and adaptive immunity, inflammatory cytokine, chemokine, and cell-killing signaling pathways were all stimulated by IFN-α administration after TG immunization of CBA mice. SIGNIFICANCE: We confirmed the remarkable effects of IFN-α in both initiating thyroid immunity and modulating thyroid function and immunoregulatory signatures in established autoimmune thyroiditis. We suggest that IFN-α should be administered with caution in clinical settings.

Differential serum interferon-ß levels in autoimmune thyroid diseases.

Introduction: Interferon (IFN)-ß is known as an environmental trigger for the occurrence of autoimmune thyroid disease (AITD). However, the association of another type-1 IFN, IFN-ß, with AITD is unknown. Material and methods: In the study, we explored the association of serum IFN-ß levels with AITD in an ethnic Chinese (i.e., Taiwanese) population. We enrolled 160 patients with Graves' disease (GD), 47 patients with Hashimoto's thyroiditis (HT), and 119 healthy controls. Serum IFN-ß and B-cell activating factor (BAFF) levels were quantified in healthy controls at the baseline and in patients with AITD either prior to receiving medication or while under medication. Thyroid function and thyroid-stimulating hormone receptor antibody (TSHRAb) levels were measured at the time of serum collection. Results: Serum IFN-ß levels were lower in the HT group than in the control group (p = 0.031). A significant inverse correlation was observed between IFN-ß and TSHRAb levels in men with GD (r = -0.433, p = 0.044). Serum IFN-ß levels were also negatively associated with BAFF levels in men with GD, HT, and AITD (r = -0.320, p = 0.032; r = -0.817, p = 0.047; and r = -0.354, p = 0.011, respectively), but not in women with GD, HT, or AITD. Conclusions: Serum IFN-ß levels were lower in HT patients. Correlations of serum IFN-ß with TSHRAb and BAFF levels were found to be gender-specific. Further well-designed studies with larger sample sizes are required to confirm our findings.

Prevalence and risk factors for latent tuberculosis among diabetes patients in Taiwan: A cross-sectional study.

INTRODUCTION: Diabetes mellitus (DM) is a known risk factor for tuberculosis (TB), leading to an approximate three-fold higher risk of developing active TB. However, epidemiological studies on the prevalence of latent TB infection (LTBI) in DM patients are lacking. In this study, we investigated the presence of LTBI and determined risk factors for LTBI in DM patients. METHODOLOGY: We conducted a cross-sectional study at Taipei Medical University-Shuang Ho Hospital in northern Taiwan. The study population comprised DM patients (aged 20-70 years) attending a metabolism outpatient clinic between February 2011 and February 2013, excluding patients who were suspected or confirmed to have active TB. Venous blood samples were drawn from patients to detect LTBI using the QuantiFERON-TB Gold In-Tube (QFT-GIT) method. RESULTS: We enrolled 1120 patients with DM. The QFT-GIT showed positive results for 241 people (21.5%) and negative results for 879 people (78.5%). The mean age at QFT-GIT positivity was 58.2 years, which was significantly dissimilar to the mean age at QFT-GIT negativity, which was 55.0 years (p < 0.001). Multivariate logistic regression indicated that the trend of QFT-GIT positivity increased after the age of 50 years. Effective glycemic control did not differ significantly between QFT-GIT-positive and -negative patients. Moreover, men were predominant were predominant in both QFT-GIT-positive and -negative patients. CONCLUSIONS: More than one-fifth of DM patients have LTBI. Among the DM patients, those older than 50 years may have a higher risk of LTBI. Moreover, effective glycemic control did not differ significantly in patients with LTBI.