Trajectory patterns of metabolic syndrome severity score and risk of type 2 diabetes.

BACKGROUND: The available evidence indicates that the severity of metabolic syndrome tends to worsen progressively over time. We assessed the trajectory of age and sex-specific continuous MetS severity score (cMetS-S) and its association with the development of diabetes during an 18-year follow-up. METHODS: In a prospective population-based Tehran Lipid and Glucose Study, 3931 eligible participants free of diabetes, aged 20-60 years, were followed at three-year intervals. We examined the trajectories of cMetS-S over nine years using latent growth mixture modeling (LGMM) and subsequent risks of incident diabetes eight years later. The prospective association of identified trajectories with diabetes was examined using the Cox proportional hazard model adjusting for age, sex, education, and family history of diabetes, physical activity, obesity (BMI ≥ 30 kg/m2), antihypertensive and lipid-lowering medication, and baseline fasting plasma glucose in a stepwise manner. RESULTS: Among 3931 participants, three cMetS-S trajectory groups of low (24.1%), medium (46.8%), and high (29.1%) were identified during the exposure period. Participants in the medium and high cMetS-S trajectory classes had HRs of 2.44 (95% CI: 1.56-3.81) and 6.81 (95% CI: 4.07-10.01) for future diabetes in fully adjusted models, respectively. Normoglycemic individuals within the high cMetS-S class had an over seven-fold increased risk of diabetes (HR: 7.12; 95% CI: 6.05-12.52). CONCLUSION: Although most adults exhibit an unhealthy metabolic score, its severity usually remains stable throughout adulthood over ten years of follow-up. The severity score of metabolic syndrome has the potential to be utilized as a comprehensive and easily measurable indicator of cardiometabolic dysfunction. It can be employed in clinical settings to detect and track individuals at a heightened risk of developing T2DM, even if their glucose levels are normal.

The impact of metabolic syndrome on chronic kidney disease development. Insights from a big prospective study.

BACKGROUND: Chronic kidney disease (CKD) can progress over time and cause renal replacement therapy. Studies showed the association between metabolic syndrome (MetS) and CKD. Current evidence is from cross-sectional studies. There is a need for the robust data from big prospective cohort studies with long-term follow-up. This study investigated the association between CKD and MetS after 18 years of follow-up. MATERIAL AND METHOD: Among 15,255 participants aged ≥20 years at baseline (1999-2005), after exclusion of CKD, cancer, and use of corticosteroids, 8987 participants entered the study and followed at a three-year cycle up to 2018. All participants were divided into five subgroups: (1) MetS-free, (2) MetS (DM+, HTN-), (3) MetS+ (DM-, HTN+), (4) MetS+ (DM+, HTN+) and (5) MetS+ (DM-, HTN-). RESULT: At baseline, the mean age of the participants was 39.8 ± 13.3 years; 4996 (55.6%) were females. CKD was developed in 2038 (22.7%) subjects during 18 years of follow-up, of whom 1107 had MetS. After adjusting for the confounding variables, MetS (DM+, HTN+) subgroup had the highest risk of CKD (HR = 1.51, 95% CI = 1.32-1.71). MetS subjects with five components had a higher incidence rate of CKD (HR = 1.43, 95% CI = 1.22-1.68). There was no association between high waist circumference (WC) (HR = 1.08, 95% CI = 0.99-1.19) and high-density lipoprotein (HDL) (HR = 1.07, 95% CI = 0.98-1.18) with CKD. CONCLUSION: CKD significantly develops in patients with MetS. Metabolic syndrome was associated with the development of chronic kidney disease incidence. Hypertension, diabetes, and age were strong indicators, while abdominal obesity and reduced HDL were not associated with the incidence of CKD.

Pharmacodynamic and pharmacokinetic properties of the combined preparation of levothyroxine plus sustained- release liothyronine; a randomized controlled clinical trial.

BACKGROUND: Understanding pharmacokinetics (PK) and pharmacodynamics (PD) of the sustained-release liothyronine (SR-T3) is of paramount importance to design therapeutic regimens that are able to simulate normal thyroid hormone secretion while avoiding excursions in the T3 serum concentration. Here, we designed a parallel randomized clinical trial to characterize the PK and PD of the combined preparations of LT4 + SR-T3 in hypothyroid patients. METHODS: Radioiodine-treated hypothyroid patients over 20 years of age, who attained euthyroidism with LT4 monotherapy were recruited from the Endocrine Clinic in Tehran. The patients were allocated to two intervention groups of group A: 9 µg SR-T3 plus 68.5 µg LT4 (ratio 1:7.5) and group B: 12 µg SR-T3 plus 60 µg LT4 (ratio 1:5), and a control group with LT4 monotherapy. For PD study, thyroid hormone profile was evaluated at 8 and 12 weeks intervals after intervention. To assess PK properties of SR-T3, T3-Cmax, T3-Tmax and AUC0 - 24 were calculated at the last visit. RESULTS: Serum T4 and FT4 concentrations decreased in the intervention groups after 3 months. No significant difference was observed in serum T3 and FT3 concentrations before and after intervention. Serum T3/T4 ratio increased significantly in the intervention groups after intervention, with the highest increase in group B from 8.6 ± 2.03 at baseline to 12.2 ± 1.6. Comparison of trial groups at follow-up showed no differences in serum TSH, T4, T3 and T3/T4 concentrations among different groups. During 24 h, minimal variation in serum T3 concentration was observed in group B with mean ∆T3 of 15.4 ± 10.5 ng/dl. T3-Tmax, T3-Cmax and AUC0 - 24 in the combined sustained-release preparation were 4.38 ± 1.1 h., 101.0 ± 5.7 ng/dl and 2257 ± 110 ng.h/L, respectively which were significantly different from the control group. CONCLUSION: Combined treatment with a single dose of SR-T3 plus LT4 is associated with increased serum T3/T4 ratio and minimal excursions in serum T3 concentration during 24 h; however, it was not significantly different from the control group. To incorporate sustained-release T3 in the management of hypothyroidism, a higher ratio of SR-T3 to LT4 than that of the previously recommended by the international organizations is suggested. IRCT REGISTRATION NUMBER: IRCT20100922004794N13. https://www.irct.ir/search/result?query=IRCT20100922004794N13 . Registration date: 08/12/2021.

Long-Term Follow-up of Graves Orbitopathy After Treatment With Short- or Long-Term Methimazole or Radioactive Iodine.

OBJECTIVE: The aim of this study was to compare long-term outcomes in terms of new onset or worsening of Graves orbitopathy (GO) in patients with Graves disease treated with different therapeutic modalities for hyperthyroidism. METHODS: A total of 1163 patients with Graves disease were enrolled in this study; 263 patients were treated with radioiodine and 808 patients received methimazole (MMI) therapy for a median of 18 months, of whom 178 patients continued MMI for a total of 96 months (long-term methimazole [LT-MMI]). The thyroid hormonal status and GO were evaluated regularly for a median of 159 months since enrollment. RESULTS: The rates of relapse, euthyroidism, and hypothyroidism at the end of follow-up were as follows: radioiodine treatment group: 16%, 22%, and 62%, respectively; short-term MMI group: 59%, 36%, and 5%, respectively; and LT-MMI group: 18%, 80%, and 2%, respectively. During the first 18 months of therapy, worsening of GO (11.5% vs 5.7%) and de novo development of GO (12.5% vs 9.8%) were significantly more frequent after radioiodine treatment (P <.004). Overall worsening and de novo development of GO from >18 to 234 months occurred in 26 (9.9%) patients in the radioiodine group and 8 (4.5%) patients in the LT-MMI group (P <.037). No case of worsening or new onset of GO was observed in patients treated with LT-MMI from >60 to 234 months of follow-up. CONCLUSION: Progression and development of GO were associated more with radioiodine treatment than with MMI treatment; GO may appear de novo or worsen years after radioiodine treatment but not after LT-MMI therapy.

Vitamin D Receptor (VDR) Allelic Variants Correlating with Response to Vitamin D3 Supplementation in Breast Cancer Survivors.

We investigated how vitamin D receptor (VDR) allelic variants affect breast cancer survivors' responses to vitamin D3 supplementation to increase circulating 25-hydroxy vitamin D (25(OH)D) levels. Two hundred and fourteen patients who were diagnosed with breast cancer at least 6 mo, prior to the study and had completed all treatment regimens were assigned to consume 4000 IU of vitamin D3 daily for 12 weeks. Linear and multinomial logistic regression analyses were used to analyze the association of VDR single nucleotide polymorphism (SNPs) with changes in circulating 25(OH)D. The TaqI and BsmI VDR sequence variants modified the effect of vitamin D3 treatment on the plasma 25(OH)D changes (P value = 0.008 for TaqI and P value = 0.0005 for BsmI). Patients with the bb [Q4 vs. Q1 odds ratio(OR) 8.04, 95% confidence interval (CI) 1.55-41.57] and tt [Q4 vs. Q1 OR 4.64 95%CI 1.02-21.02] genotype of BsmI and TaqI had larger increases in plasma 25(OH)D levels compared to those with BB and TT genotype respectively after adjustment for potential confounders. Haplotype analyses suggested the existence of specific combination of alleles that might be associated with circulating 25(OH)D changes. VDR allelic variants modulate vitamin D3 supplementation to increase plasma 25(OH) levels in breast cancer survivors.

Time to Normalization and Sustainable Normal Serum Thyrotropin Concentrations in Patients with Hyperthyroidism: Comparison of Methimazole and Radioactive Iodine Treatments.

OBJECTIVE: The aim of this study was to compare the "time to euthyroidism" and "time spent in euthyroidism" following methimazole (MMI) and radioactive iodine (RAI) treatments. METHODS: Three hundred fifty-eight patients with hyperthyroidism, 178 who underwent long-term MMI treatment and 180 patients who underwent RAI treatment, were analyzed. The time to normalization of increased serum values of free thyroxine and triiodothyronine and suppressed serum thyroid-stimulating hormone (TSH) values as well as the percentage of time that the thyroid hormone levels remained within normal ranges during a mean follow-up time of 12 years were compared. RESULTS: The mean time to euthyroidism was 4.59 ± 2.63 months (range, 2-16 months) in the MMI group and 15.39 ± 12.11 months (range, 2-61 months) in the RAI group (P < .001). During follow-up, the percentage of time spent in euthyroidism was 94.5% ± 7.3% and 82.5% + 11.0% in the MMI and RAI groups, respectively (P < .001). Serum TSH values above and below the normal range were observed in 5.3% and 0.2% of patients, respectively, in the MMI group and 9.8% and 7.7% of patients, respectively, in the RAI group (P < .001). The time to euthyroidism and the percentage of time spent in euthyroidism in 40 RAI-treated patients with euthyroidism were similar to those in the MMI group and significantly shorter than those in the RAI-treated hypothyroid and relapsed subgroups. In patients who continued MMI therapy for >10 years, the percentage of time spent in euthyroidism was >99%. CONCLUSION: In our cohort of selected patients, MMI therapy was accompanied by faster achievement of the euthyroid state and more sustained normal serum TSH levels during long-term follow-up compared with RAI therapy.

Does Motivational Interviewing Improve the Weight Management Process in Adolescents? A Systematic Review and Meta-analysis.

BACKGROUND: Due to the complex nature and high heterogeneity of motivational interviewing (MI) trials, available data on the effectiveness of these interventions on weight management in the early years of life is not yet conclusive. This study aimed to (1) evaluate the effectiveness of MI-based interventions on modifying obesity-related behaviors and consequently controlling weight in adolescents, and (2) determine characteristics of participants and interventions through sub-group analysis. METHODS: Electronic databases, i.e., Medline, Elsevier, ISI, Cochrane Central Register of Controlled Trials (Clinical Trials), PsycINFO, and subject-related key journals were searched for randomized controlled trials that investigated the effect of MI-based interventions on weight management in overweight/obese adolescents. Primary outcomes were BMI, BMI Z-score, waist circumference, and fat percentage. Secondary outcomes were related behaviors (dietary intake and physical activity) and cognitive abilities (self-efficacy, self-regulation, self-control). Of the 3673 studies initially screened for eligibility, nineteen studies met the inclusion criteria and eighteen studies were entered in the meta-analysis. Meta-regression and sub-group analyses were conducted to control the high heterogeneity of studies. Sensitivity analysis has been conducted based on the Cochrane guidelines using the leave-one-out methods. RESULTS: MI-based interventions did not affect on all primary outcomes, including BMI, BMI Z-score, waist circumference, and fat percentage; however, in terms of secondary outcomes, only sugary beverage intake was reduced in adolescents (SMD = - 0.47, K = 3, I2 = 26.2%). Physical activity and cognitive variables were not considered in the current analysis due to limited data and high heterogeneity in measurements and reports. In addition, findings of sensitivity results showed that MI could significantly reduce waist circumference among adolescents (SMD = - 0.51, 95% CI - 0.91 to - 0.11). In terms of subgroup analysis, our results showed that various characteristics of participants (age, sex, weight status) and interventions (parental involvement, study duration, fidelity assessment, type of the control groups) could affect related primary and secondary outcomes among adolescents. CONCLUSION: MI-based behavioral interventions had minor effects on reducing sugary beverage intake in all adolescents while a reduction in central obesity was noted predominantly among girls and those with complete participation. The current results indicate that the main characteristics influencing goal achievement in MI interventions are the age of participants, MI fidelity assessment, parental involvement, duration of interventions, and type of the control groups.

RAP1GAP Functions as a Tumor Suppressor Gene and Is Regulated by DNA Methylation in Differentiated Thyroid Cancer.

Inactivation of tumor suppressor genes, such as RAP1GAP, by hypermethylation of their regulatory region can give rise to thyroid tumors. The aim of this study was to investigate the expression of the RAP1GAP gene and the DNA methylation patterns of its CpG74a, CpG74b, and CpG24 in an Iranian population with differentiated thyroid cancer (DTC). In this study, 160 individuals who underwent thyroidectomy in the Tehran Erfan Hospital between 2018 and 2020 were selected. DNA methylation patterns of selected CpG islands (CpG74a, CpG74b, and CpG24) were determined using methylation-specific PCR. The mRNA expression and protein level of -RAP1GAP were also evaluated. SW1736 and B-CPAP cells were treated with 5-aza-2'-deoxycytidine (5-Aza) to demethylate these regions. The hypermethylation rates of CpG74a and CpG24 in DTC samples were significantly higher than in the control. The mRNA expression and protein level of -RAP1GAP were significantly decreased in the DTC group. In the DTC group, hypermethylation in CpG74a was correlated with decreasing RAP1GAP expression (R2: 0.34; p = 0.043). CpG74a with a specificity of 86.4% has significant prediction power to distinguish between DTC and normal thyroid tissues. Additionally, hypermethylation of CpG74a was significantly associated with higher tumor stages (stage III-IV: 77%; stage I-II: 23%; p = 0.012). Increasing expression of RAP1GAP after demethylation with 15 µM of 5-Aza was observed in both cell lines. These results indicate that DNA hypermethylation in CpG74a can be considered as an epigenetic biomarker in DTC.

Cumulative Effects of Thyroid Hormones Over 10 Years and Risk of General and Abdominal Obesity.

We aimed to assess if changes in thyrotropin (TSH) and free thyroxine (FT4) over 10 years of follow-up would be associated with changes in body mass index (BMI) and waist circumference (WC) or risk of obesity. We enrolled 2317 out of 4179 participants in Tehran Thyroid Study with serum TSH between 0.1-10 mU/l and without history of thyroid medication or surgery. Serum concentrations of FT4 and TSH were measured at baseline and three follow-ups (1999-2011). To account for within-subject correlation, the generalized estimating equation was used to assess the association between one standard deviation(SD) change in the main exposures [cumulative excess (CE)TSH and CEFT4] and changes in BMI and WC; calculated scores of CETSH and CEFT4 were included in models as time-varying exposures. Cumulative excess of TSH or FT4 was not associated with increased incidence of general or abdominal obesity. However, CEFT4 was negatively associated with BMI only in overweight and obese subjects. In GEE analysis, one unit increase in TSH was associated with 0.02 kg/m2 increase in BMI (95% CI: 0.01, 0.03), which remained significant only in women; although the association was not significant after adding FT4 to model. One unit increase in FT4 was associated with 1.5 kg/m2 decrease in BMI (95% CI:-1.8,-1.2) and 4.1 cm decrease in WC (95% CI:-5.1,-3.1) in both sexes independent of TSH and other confounders. Cumulative excess of TSH or FT4 indicated no risk for general or abdominal obesity. However, FT4 was negatively associated with BMI and WC independent of TSH.

Control of Graves' hyperthyroidism with very long-term methimazole treatment: a clinical trial.

BACKGROUND: Long-term antithyroid drug therapy has become one of the options for treatment of Graves' hyperthyroidism. The aim of this study was to compare thyroid status in those who discontinued methimazole (MMI) treatment after 12.8 years with those who continued MMI as long as 24 years. METHODS: Fifty nine patients with Graves' disease on long-term MMI for 14.2 ± 2.9 years were recruited; 32 patients (54%) decided to discontinue MMI and 27 (46%) preferred additional years of MMI treatment. All patients were followed for a mean of 6 additional years. RESULTS: Of 27 patients who continued MMI up to 24 years, suppressed serum thyrotropin (TSH) was not observed in any patient after the seventh year of treatment. Serum free thyroxine, triiodothyronine, TSH and TSH receptor antibody concentrations remained normal up to the length of the study. Mean daily dose of MMI to maintain TSH in the reference range decreased gradually and reached to 2.8 ± 1.7 mg by 24 years of MMI treatment. No adverse reaction related to MMI occured during additional years of therapy. In 32 patients who discontinued MMI, hyperthyroidism relapsed in 6 patients (19%), one left follow-up and 25 (78%) remained euthyroid during the study. CONCLUSIONS: Long-term low dose MMI treatment may be a lifelong effective and safe therapeutic modality in patients with Graves' hyperthyroidism for prevention of relapse, if studies from other centers confirm findings of this research. TRIAL REGISTRATION: IRCT201009224794N1, 2010-10-25. Retrospectively registered. https://www.irct.ir/trial/5143 .

Persistent hypercalcemia with similar familial Hypocalciuric hypercalcemia features: a case report and literature review.

BACKGROUND: Primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) are the most important differential diagnosis of parathyroid hormone (PTH)-dependent hypercalcemia. The clinical features of FHH and PHPT can overlap in some cases. Therefore, these two diseases must be differentiated to prevent unnecessary parathyroidectomy. Here, we present a case that was not entirely matched with any of the known differential diagnoses of hypercalcemia. CASE PRESENTATION: A 19-year-old girl with no history of any disease presented with persistent hypercalcemia without any specific musculoskeletal complaint. We found persistent hypercalcemia in her routine laboratory data from 3 years ago; while no data was available during the childhood period. Her dietary calcium intake was normal. She did not mention any history of renal stone, bone fracture as well as family history of hypercalcemia. Biochemical features showed normal values of serum creatinine, high normal serum calcium (range, 10.3-11.3 mg/dL; (normal range: 8.8-10.4)), and non-suppressed PTH levels (range, 37.2-58.1 pg/mL; (normal range: 10-65)). Serum 25 OH vitamin D level at the first visit was 16.1 ng/mL that treated by vitamin D supplementation. Since then, all 25 OH vitamin D levels were in the acceptable range. After correction of vitamin D deficiency during the follow-up period the calcium creatinine clearance ratio(s) (CCCR) were calculated in the range of 0.009 to 0.014 (means below 1%). The clinical and laboratory data indicate more FHH rather than PHPT. Genetic studies were negative for the common genes associated with FHH (CASR, GNA11, and AP2S1 genes) and multiple endocrine neoplasia type1 (MEN1). On the other hand, no evidence of autoimmunity was found in her to support an autoimmune FHH-like syndrome. Hence, the case did not match completely to any diagnosis of FHH and PHPT, so we decided to follow her. CONCLUSION: We presented a patient with FHH phenotype whose common genetic tests were negative. Further research is needed to ascertain other causes leading to similar manifestations.

Investigating the prevalence of primary thyroid dysfunction in obese and overweight individuals: Tehran thyroid study.

BACKGROUND: Due to the increasing worldwide prevalence of obesity, it is essential to determine the prevalence of obesity-related thyroid dysfunctions. The purpose of this study was to investigate the prevalence of thyroid dysfunctions, namely hypothyroidism and hyperthyroidism, and their association with BMI among adult Iranian overweight and obese individuals. METHOD: This cross-sectional study was carried out within the framework of the Tehran Thyroid Study (TTS); 5353 participants (57.5% female) entered our study. Anthropometric measurements were performed. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) were assayed. We categorized individuals into 3 BMI groups (normal-weight, overweight and obese), then calculated prevalence rate, odds ratio (OR), and 95% confidence interval (CI) for outcomes in overweight and obese groups. The normal-weight group was used as the control group. RESULTS: We found a higher prevalence of hypothyroidism (11.6% vs 8.2% Total, 4.0% vs 1.1% overt and 7.6% vs 7.1% subclinical, P < 0.001) and TPOAb positivity (17.3% vs 11.6%, P < 0.001) in obese participants compared with normal-weight participants. Hyperthyroidism's overall prevalence was 4.2, 5.7, and 4.9% in obese, overweight, and normal-weight groups, respectively. Obesity was associated with higher odds of overt hypothyroidism (OR: 2.0, 95% CI: 1.15-3.49, P < 0.05) and TPOAb positivity (OR: 1.29, 95% CI: 1.04-1.60, P < 0.05) after adjusting for confounding variables. In contrast, no association was observed between the overweight group and the odds of hypothyroidism and TPOAb positivity in the adjusted results. CONCLUSIONS: Obesity was associated with an increased risk of overt hypothyroidism and TPOAb positivity.

The association between subclinical hypothyroidism and TPOAb positivity with infertility in a population-based study: Tehran thyroid study (TTS).

BACKGROUND: Thyroid autoimmunity(TAI) is the most prevalent autoimmune condition in women of fertile age. There are increasing data regarding the association of thyroid dysfunction and thyroid autoimmunity with adverse pregnancy outcomes but there is no consensus regarding infertility and TPOAb positivity; thus we aimed to evaluate the association between thyroid TPOAb positivity and infertility in females and males in a population-based study (TTS). METHODS: Cross-sectional study of 3197 female and male participants in Tehran Thyroid Study (TTS) at the framework of the Tehran Lipid and Glucose Study (TLGS). Data included biochemical measurements and a self-administered questionnaire. RESULTS: A total of 12,823 cases in phase 4, 3719 cases (2108 female and 1611 male) were analyzed. The mean TSH of the infertile female and male was 2.52 ± 2.68 µIU/ml and 3.24 ± 10.26 µIU/ml respectively. The TPO median(IQR) of women with and without a history of infertility were 6.05 (3.30-13.96)and 6.04 (3.17-11.15);(P = 0.613), they were 5.08 (3.20-125.68) and 5.31 (3.93-125.68);(P = 0.490) in male participants, respectively. Results of crude and adjusted logistic regression analysis of the development of infertility by thyroid function and TPOAb, except for fT4 in male subjects, depicted no association between infertility and other variables in both crude and adjusted models. CONCLUSION: Based on the result, thyroid autoimmunity was not associated with infertility in both females and males.

Determination of age and sex specific TSH and FT4 reference limits in overweight and obese individuals in an iodine-replete region: Tehran Thyroid Study (TTS).

Introduction: To determine age and sex-specific thyrotropin (TSH) and free thyroxine (FT4) reference ranges according to body mass index (BMI) categories. Methods: With regards to the National Academy of Clinical Biochemistry (NACB) criteria, a total of 2818 individuals from the Tehran Thyroid Study population was selected and categorized in three BMI groups. Results: TSH levels did not differ significantly between BMI groups (p = .054). Females had statistically higher TSH levels than males in all BMI categories (p < .001). According to age-specific analyses, the youngest category (20-29 years) had the highest median values of serum TSH in all BMI groups. With increasing BMI, the 2.5th percentile of TSH remained approximately unchanged and the 97.5th percentile showed an increasing pattern. FT4 level was significantly higher in the normal weight group compared to obese individuals (p < .001); females had significantly lower FT4 levels than males in normal weight and obese groups (p < .001). According to age categories, the youngest group (20-29 years) had higher levels of FT4 than the elderly group in all BMI categories. A decreasing pattern in both 2.5th and 97.5th percentiles of FT4 was observed along with increasing BMI. Conclusions: Compared to the normal weight population, obese individuals have slightly lower FT4 concentrations accompanied by similar TSH levels. With increasing BMI, upper limits of TSH and FT4 show increasing and decreasing patterns, respectively.

Assessment of the simultaneous effect of hypothyroidism and thyroid autoimmunity with gestational diabetes on the incidence of type 2 diabetes.

INTRODUCTION: Despite the evidence available on the adverse impact of gestational diabetes (GDM) and thyroid disorders on developing type 2 diabetes (T2DM), the concurrent influence of these disorders on the incidence of T2DM has not been reported yet. METHODS: In this prospective study, 1894 non-diabetic women aged 20 to 60 years, with a history of at least one term delivery, without diagnosed hyperthyroidism were selected at the initiation of the Tehran Thyroid Study (TTS). Pooled logistic regression analyses were used to investigate the association of GDM, thyroid disorders i.e., hypothyroidism and/or thyroid peroxidase antibody (TPOAb) positivity and interaction between GDM and thyroid disorders with the risk of incident T2DM. RESULTS: Of the 1894 participants of the present study, 346 (18.3%) had a history of GDM, and 832 (43.9%) had thyroid disorders. The total cumulative incidence rate of T2DM at the median follow-up time of ~ 12 years was overall 12/1000 person-years (95% confidence interval (CI): 10/1000-13/1000), with an incidence rate of 16/1000 (95%CI: 13/1000-20/1000) in women with GDM; and 11/100,000 (95%CI: 9/100,000-12/1000) among those without GDM. After adjustment for age, the risk of incident T2DM increased among individuals with the previous GDM compared to women without a history of GDM (odds ratio (OR): 1.54, 95%CI: 1.06, 2.25). No significant associations were found between either thyroid disorders or the interaction between GDM and thyroid disorders with the development of T2DM; (OR: 1.14, 95%CI: 0.82, 1.58) and (OR: 1.27, 95%CI: 0.66, 2.43), respectively. CONCLUSION: GDM and thyroid disorders have no concurrent impacts on the incidence of T2DM.

Abdominal Obesity Phenotypes and Incidence of Thyroid Autoimmunity: A 9-Year Follow-up.

PURPOSE: The association between obesity and autoimmune diseases has been suggested by several previous studies. The objective of our study was to assess the association of abdominal obesity phenotypes with thyroid autoimmunity. MATERIALS AND METHODS: This study was conducted within the framework of a population-based cohort study, Tehran Thyroid Study (TTS) on 4708 subjects without thyroid autoimmunity at baseline. Participants were categorized into four abdominal obesity phenotypes according to waist circumference (WC) and other metabolic syndrome components. Serum concentrations of thyroid peroxidase antibody (TPOAb), free T4 (FT4), thyrotropin (TSH), glucose, and lipid profiles were measured after 3, 6 and 9 years of follow-up. Cox proportional hazard models were used to evaluate associations of different phenotypes with the incidence of thyroid autoimmunity, adjusted for age, sex, FT4, and TSH. RESULTS: Highest and lowest incidence rates of TPOAb positivity were observed among metabolically unhealthy, non-abdominally obese (MUNAO) [8.78 (7.31-10.55) per 1000 person-years of follow-up] and metabolically unhealthy abdominally obese (MUAO) [4.98 (3.88-6.41) per 1000 person-years of follow-up] phenotypes. Considering the metabolically healthy non-abdominal obese (MHNAO) individuals as reference, none of metabolically healthy abdominally obese (MHAO), MUNAO, and MUAO phenotypes were associated with increased risk of developing TPOAb positivity. Compared to individuals with high WC, the incidence rate (95%CI) of TPOAb positivity was higher among those with normal WC: 8.44 (7.13-10.0) vs 5.11 (4.01-6.51) per 1000 person-years, respectively. Higher WC was not associated with incident TPOAb positivity. CONCLUSION: There was no significant association between baseline abdominal obesity phenotype status and development of TPOAb positivity over 9 years of follow-up.

Can Supplementation with Vitamin D Modify Thyroid Autoantibodies (Anti-TPO Ab, Anti-Tg Ab) and Thyroid Profile (T3, T4, TSH) in Hashimoto's Thyroiditis? A Double Blind, Randomized Clinical Trial.

Hashimoto's thyroiditis (HT) is the most prevalent autoimmune disorder characterized by the destruction of thyroid cells caused by leukocytes and antibody-mediated immune processes accompanied by hypothyroidism. In recent years, evidence has emerged pointing to various roles for vitamin D, including, proliferation and differentiation of normal and cancer cells, cardiovascular function, and immunomodulation. Vitamin D deficiency has been especially demonstrated in HT patients. The aim of this study was to investigate the effect of vitamin D on circulating thyroid autoantibodies and thyroid hormones profile (T4, T3, and TSH) in females with HT. Forty-two women with HT disease were enrolled in this randomized clinical trial study and divided into vitamin D and placebo groups. Patients in the vitamin D and placebo groups received 50 000 IU vitamin D and placebo pearls, weekly for 3 months, respectively. The serum levels of 25-hydroxy vitamin D [25(OH) D], Ca++ion, anti-thyroperoxidase antibody (anti-TPO Ab), anti-thyroglobulin antibody (anti-Tg Ab), T4, T3, and TSH were measured at the baseline and at the end of the study using enzyme-linked immunosorbent assays. The results of this study showed a significant reduction of anti-Tg Ab and TSH hormone in the Vitamin D group compared to the start of the study; however, there was a no significant reduction of anti-TPO Ab in the Vitamin D group compared to the placebo group (p=0.08). No significant changes were observed in the serum levels of T3 and T4 hormones. Therefore, vitamin D supplementation can be helpful for alleviation of the disease activity in HT patients; however, further well controlled, large, longitudinal studies are needed to determine whether it can be introduced in clinical practice.

Long-Term Variations of Antithyroperoxidase Antibodies and its Clinical Significance.

Various cut-offs have been proposed for thyroid peroxidase antibodies (TPOAb) positivity. Considering that the long-term trend of TPOAb levels and its positivity incidence is not clearly understood, we conducted the current study to determine the longitudinal variations of TPOAb in a population-based cohort study. We followed 5783 individuals of Tehran Thyroid cohort Study (TTS) for 10 years (4 phases). After exclusions, data of 3493 euthyroid participants remained for analyses. The baseline prevalence rates of TPOAb positivity were 19.8, 17, and 11.4% and the annual incidence rates (95% CI) of TPOAb positivity were 8.53 (8.29-8.77), 7.59 (7.37-7.80) and 6.79 (6.60-6.98) per 1000 persons for the 3 proposed cut-offs of 14.77, 18.38, and 40 U/l; respectively. Although a slightly increasing trend was observed for TPOAb levels (p=0.001) and its conventional positivity (TPOAb>40U/l), the recently proposed cut-offs of 14.77 and 18.38 U/l showed constant TPOAb positivity over 10 years. The time trends of the TPOAb levels among younger participants were significantly different from older participants (time×age effect p=0.004), with the former having an increasing trend and the latter, a relatively decreasing trend. Although the prevalence of TPOAb positivity was significantly (p<0.001) higher among women as compared to men, the longitudinal changes of TPOAb were similar in men and women. TPOAb positivity along with TSH values between 2.5 and 5.0 mU/l or free T4 values between 0.93 and 1.7 ng/dl exerted a significantly increased risk of subclinical or overt hypothyroidism. In an iodine sufficient population, an increasing trend in TPOAb levels was observed in line with the increasing incidence of subclinical and overt hypothyroidism.

Correction to: Vitamin D receptor gene polymorphisms affecting changes in visceral fat, waist circumference and lipid profile in breast cancer survivors supplemented with vitamin D3.

Following publication of the original article [1], the authors reported that one of the co-authors has a mistake in the author name.

Vitamin D receptor gene polymorphisms affecting changes in visceral fat, waist circumference and lipid profile in breast cancer survivors supplemented with vitamin D3.

OBJECTIVE: We investigated whether vitamin D receptor (VDR) polymorphisms are associated with circulating metabolic biomarkers and anthropometric measures changes in breast cancer survivors supplemented with vitamin D3. METHODS: One hundred sixty-eight breast cancer survivors admitted to Shohaday-e-Tajrish hospital received 4000 IU of daily vitamin D3 supplements for 12 weeks. Anthropometric measurements as well dietary, physical activity and plasma metabolic biomarkers assessments were performed before and after intervention. VDR polymorphisms were considered as the main exposures. Multivariate multiple linear regression analyses were used to determine the association between the VDR single-nucleotide polymorphisms (SNPs) and changes in metabolic and anthropometric measures in response to vitamin D3 supplementation. RESULTS: One hundred twenty-five (85%) women had insufficient and inadequate levels of plasma 25-hydroxy vitamin D (25(OH)D) at baseline. Compared to the AA genotype of the ApaI, the aa category showed greater increase in muscle mass [71.3(10.7131.9)] and higher decrease in LDL-C [- 17.9(- 33.6, - 2.3)] levels after adjustment for potential confounders. In addition, the heterozygous genotype (Bb) of the BsmI VDR was associated with higher increase in WC following vitamin D3 supplementation, compared to BB [2.7(0.1,5.3)]. Haplotype score analyses indicate a significant association between inferred haplotypes from BsmI, ApaI, TaqI and FokI, BsmI and Cdx2 VDR polymorphisms and on-study visceral fat changes. CONCLUSIONS: Findings of this study showed that genetic variation in the VDR gene was associated with changes in cardio-metabolic parameters in breast cancer survivors, supplemented with vitamin D3, results could provide a novel insight into better understanding of which subset of individuals benefit most from normalization of vitamin D status. TRIAL REGISTRATION: This trial has been registered on the Iranian Registry of Clinical Trials (IRCT) under the identification code: IRCT2017091736244N1, registration date: 2017-11-10, http://www.irct.ir/trial/27153 and was approved by the ethics committees of the National Nutrition and Food Technology Research Institute (NNFTRI), Shahid Beheshti University of Medical Sciences (SBMU).