Ladan Mehran

EDUCATION

MD,PhD

RESEARCH INTERESTS

Epidemiology, thyroid, iodine deficiency, metabolic syndrome

Scopus Publications

Association between body mass index trajectories and type 2 diabetes incidence over an 18-year follow-up in the Tehran Lipid and Glucose Study
Nafiseh Hassanloo, Ladan Mehran, Atieh Amouzegar, Hengameh Abdi, Safdar Masoumi, Fereidoun Azizi, and Seyede Parmis Maroufi
Springer Science and Business Media LLC



Interrelationship between thyroid hormones and reduced renal function, a review article
Sadaf Agahi, Atieh Amouzegar, Mohammadjavad Honarvar, Fereidoun Azizi, and Ladan Mehran
Springer Science and Business Media LLC
Abstract Background Understanding the relationship of thyroid hormones with the development of chronic kidney disease (CKD) has important clinical implications for managing patients with both thyroid and kidney dysfunction. In this review, our purpose was to provide a thorough comprehension of the interplay between thyroid hormones, thyroid dysfunctions, and CKD. Summary While there is evidence linking thyroid hormone levels to renal diseases, the association between thyroid hormones, specifically within the normal range, and the risk of CKD incidence is still a subject of debate. The Google Scholar, PubMed, Scopus, and Web of Science, were searched using the medical subject heading (MeSH) terms for the relevant keywords up to December 2023. Conclusion Based on the review, the development of CKD is more consistently associated with higher serum TSH and thereafter lower serum free T3 levels; however, its association with free T4 is more controversial. Furthermore, subclinical and overt hypothyroidisms were considerably associated with incident CKD. Hyperthyroidism and Hashimoto thyroiditis might increase the risk of CKD.


Optimal Cut-off Points of the Standardized Continuous Metabolic Syndrome Severity Score (cMetS-S) for Predicting Cardiovascular Disease (CVD) and CVD Mortality in the Tehran Lipid and Glucose Study (TLGS)
Maryam Adib, Ladan Mehran, Safdar Masoumi, Iman Vatanpoor, Fereidoun Azizi, and Atieh Amouzegar
Brieflands
Background: Metabolic Syndrome (MetS) is a prevalent condition associated with an increased risk of cardiovascular disease (CVD) and CVD mortality. Due to the limited clinical applicability of MetS, the standardized continuous metabolic syndrome severity score (cMetS-S) has the potential to provide continuous assessment of metabolic risk. Objectives: This study evaluated the optimal cMetS-S cut-off points in the Tehran Lipid and Glucose Study (TLGS) for predicting CVD and CVD mortality. Methods: The study included 7,776 participants over 30 years old at baseline, followed for 18 years. Sex-specific sensitivity (SS) and specificity (SP) of cMetS-S measures for predicting CVD and CVD mortality were evaluated using a receiver operating characteristic (ROC) curve, along with the area under the curve (AUC), employing a naive estimator and considering event failure status and MetS variables. Results: The cut-off point of cMetS-S for CVD was 0.13 (SS: 65.5%, SP: 59.6%) for the total population, 0.44 (SS: 49.6%, SP: 68.1%) for men, and 0.27 (SS: 64.2%, SP: 69.2%) for women. The cut-off point of cMetS-S for CVD mortality was 0.53 (SS: 51.3%, SP: 71.9%) for the total population, 0.76 (SS: 35.1%, SP: 76.2%) for men, and 0.28 (SS: 78.8%, SP: 66.4%) for women. The AUC (95% CI) of MetS based on the International Diabetes Federation (IDF) and Joint Interim Statement (JIS) definitions were 60.0 (65.3 - 56.8) and 61.1 (59.6 - 56.8) for CVD, and 59.3 (56.0 - 62.5) and 59.4 (56.3 - 62.6) for CVD mortality. Conclusions: The cut-off points of cMetS-S for CVD and CVD mortality differ between men and women. The cMetS-S could be a better predictive tool for CVD and CVD mortality than MetS.


Approach to the Patient Considering Long-term Antithyroid Drug Therapy for Graves' Disease
Fereidoun Azizi, Ladan Mehran, Hengameh Abdi, and Atieh Amouzegar
The Endocrine Society
Abstract Antithyroid drugs (ATD) are the treatment of choice for the majority of patients with Graves’ hyperthyroidism worldwide. However, relapse of hyperthyroidism after withdrawal of arbitrarily chosen conventional 12 to 18 months of therapy is very common. In the last 2 decades, many studies have shown that treatment with long-term ATD (LT-ATD) is effective and safe in the maintenance of euthyroidism. In addition, it has been reported that serum TSH receptor antibody may not decrease permanently before 5 to 6 years of ATD treatment, and clinical trials have shown that ≥5 years of ATD treatment is accompanied by remission in the majority of patients with Graves’ hyperthyroidism. The objective of this article is to discuss the optimal time to withdraw of conventional ATD therapy, to illustrate the decision-making of the management of recurrent hyperthyroidism, to review the proper management of LT-ATD, and to generate suggestions for lifelong ATD treatment by discussing 4 scenarios of decision-making in patients with Graves’ disease.


Independent association of metabolic syndrome severity score and risk of diabetes: findings from 18 years of follow-up in the Tehran Lipid and Glucose Study
Atieh Amouzegar, Mohmmadjavad Honarvar, Safdar Masoumi, Sadaf Agahi, Fereidoun Azizi, and Ladan Mehran
BMJ
ObjectivesThis study aimed to investigate the association between age-specific and sex-specific continuous metabolic syndrome severity score (cMetS-S) and the risk of developing type 2 diabetes mellitus (T2DM). Additionally, the study aimed to assess the added value of cMetS-S in predicting T2DM compared with traditional MetS criteria.DesignThe study used a longitudinal cohort design, following participants for 18 years.SettingThe research was conducted within the Tehran Lipid and Glucose Study, a community-based study in Tehran, Iran.ParticipantsA total of 6957 participants aged 20–60 years were included in the study.Interventions/exposuresThe cMetS-S of each participant was determined using age-specific and sex-specific equations and Cox proportional hazard regression models were used to analyse the association between cMetS-S and T2DM using continuous and quantile approaches.Primary and secondary outcome measuresThe outcome measure was the association between cMetS-S and the development of T2DM during the 18-year follow-up.ResultsA total of 1124 T2DM cases were recorded over 18 years of follow-up. In the fully adjusted model, a 1-SD increase in the cMetS-S was associated with future T2DM (HR 1.72; 95% CI 1.54 to 1.91). Men and women had HRs of 1.65 (95% CI 1.40 to 1.95) and 1.83 (95% CI 1.59 to 2.10) for T2DM per 1-SD increase in cMetS-S, respectively. Higher cMetS-S was associated with increased risk of diabetes in both prediabetic (HR 1.42;95% CI 1.23 to 1.64) and normoglycaemic individuals (HR 2.11;95% CI 1.76 to 2.54); this association was more significant in normoglycaemic individuals. Unlike the traditional-based MetS definitions, the cMetS-S improved diabetes prediction (p<0.001).ConclusionsThe cMetS-S is strongly associated with future diabetes in prediabetic and normoglycaemic individuals independent of MetS components during a long term. As the relationship between cMetS-S and T2DM is more pronounced in normoglycaemic individuals than in those with pre-diabetes, implementing the evaluation of cMetS-S can serve as an early identification tool for individuals at risk of T2DM prior to the onset of pre-diabetes.


Vitamin D and Anti-thyroid Peroxidase Antibody: Tehran Thyroid Study




Association between changes in thyroid hormones and incident type 2 diabetes using joint models of longitudinal and time-to-event data: more than a decade follow up in the Tehran thyroid study
Alireza Amirabadizadeh, Ladan Mehran, Atieh Amouzegar, Samaneh Asgari, Davood Khalili, and Fereidoun Azizi
Frontiers Media SA
BackgroundType 2 diabetes mellitus (T2DM) poses a significant public health challenge, contributing to considerable morbidity and mortality worldwide, which necessitates urgent preventive measures. Thyroid disorders, prevalent in many individuals, are intricately linked to metabolic health, yet studies on their relationship with T2DM yield inconsistent results—some suggesting an increased risk with abnormal thyroid hormone levels, while others indicate potential protective effects. This study investigated the association between changes in serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels and the incidence of type 2 diabetes mellitus.MethodsData from 1938 individuals aged ≥20 in the Tehran Thyroid Study cohort were used, spanning four examination cycles from 1999 to 2012, with three-year intervals. TSH and FT4 levels were log-transformed and modeled as time-varying exposures to study their association with incident T2DM.ResultsDuring a median follow-up of 9.43 years, 135 new T2DM cases were identified. The multivariable-adjusted joint model (JM) revealed that each unit increase in log-transformed TSH level was associated with a 25% decrease in T2DM incidence [HRs (95% CI): 0.75 (0.64-0.90)]. Conversely, each unit increase in FT4 level showed a marginally significant higher risk [1.06 (0.99-1.13); p-value=0.06].ConclusionThe findings of this study suggest that dynamic changes in serum thyroid hormones are associated with the development of T2DM. Rising TSH and decreasing FT4 over time are associated with a lower risk of diabetes. These findings suggest a complex interplay between thyroid function and the risk of T2DM, emphasizing the importance of monitoring thyroid hormone levels as a part of T2DM prevention strategies.


The association of body mass index variability with cardiovascular disease and mortality: a mediation analysis of pooled cohorts
Ladan Mehran, Mohammadjavad Honarvar, Safdar Masoumi, Davood Khalili, Fereidoun Azizi, Michael J. Blaha, and Atieh Amouzegar
Frontiers Media SA
AimWe aimed to investigate the effect of BMI variability on CVD and mortality and to explore the mediation effects of the main cardiovascular risk factors contributing to this association.MethodParticipants aged 40-65 years were pooled from three cohort studies(ARIC [Atherosclerosis Risk in Communities], MESA [Multi-ethnic Study of Atherosclerosis], and TLGS [Tehran Lipid and Glucose Study]. We employed root mean squared error of the fractional mixed model to calculate BMI variability in the measurement period. In the event assessment period, the hazard ratios for CVD and mortality were estimated using Cox proportional hazard regression models. In the next step, the mediation and interaction effects of fasting plasma glucose, total cholesterol, and systolic blood pressure were determined.ResultsA total of 19073 participants were included in this pooled analysis. During a median of 20.7 years of follow-up, 3900 (20.44%) CVD and 6480 (33.97%) all-cause mortality events were recorded. After adjusting for potential confounders, BMI variability was linked to the 1.3 (1.2-1.4) and 1.7 (1.6-1.8) increased risk of CVD and mortality, respectively. Fasting plasma glucose mediated approximately 24% and 8% of the effect of BMI variability on CVD and mortality, respectively. However, systolic blood pressure and total cholesterol did not have mediation effects in this association.ConclusionHigh BMI variability is independently associated with the development of CVD and mortality. This association is partly mediated through fasting plasma glucose. Modern cardiometabolic therapies that lower fasting glucose may reduce the risk of future CVD and mortality in individuals with high BMI variability.


Cardiometabolic-related dietary patterns and thyroid function: a population-based cross-sectional study
Nazanin Moslehi, Saba Mohammadpour, Parvin Mirmiran, Ladan Mehran, and Fereidoun Azizi
Springer Science and Business Media LLC
Abstract Background Little is known about the association of dietary patterns with thyroid function. Since thyroid function and cardiometabolic variables are inter-related, we investigated whether cardiometabolic-related dietary patterns are associated with thyroid function. Methods This cross-sectional study included 3520 Tehran Lipid and Glucose Study participants. Reduced rank regression was used to find dietary patterns with body mass index, serum fasting glucose, triglycerides, HDL-C, and systolic and diastolic blood pressures as response variables. Two patterns were retained, one based on 35 food groups (native-based pattern) and the other based on the European Prospective Investigation into Cancer and Nutrition Germany (EPIC) food grouping (n = 33). A confirmatory cardio-metabolic dietary pattern was also created according to the weight of food groups proposed by the Framingham Offspring Study (FOS). The association of each pattern with thyroid-stimulating hormone (TSH), free thyroxine, and thyroid peroxidase antibody (TPOAb) and the odds of thyroid dysfunction was examined by linear and logistic regression, respectively. Results The two exploratory dietary patterns were highly correlated and associated with greater TSH levels in euthyroid participants. The adjusted odds ratio (95% CI) of subclinical hypothyroidism per one standard deviation was 1.14 (1.01, 1.28) for the native-based pattern and 1.16 (1.03, 1.31) for the EPIC-based pattern. The odds of subclinical hypothyroidism was significantly greater in the second and third tertiles of the native-based pattern compared to the first tertile in the adjusted model (p-trend = 0.005). The odds of subclinical hypothyroidism increased across the tertiles of the EPIC-based pattern, but the odds was significantly higher only in tertile 3 compared to tertile 1, with an OR (95% CI) of 1.44 (1.07, 1.94) in the adjusted model. The adjusted odds of clinical hypothyroidism were greater in tertile 3 of the native-based pattern compared with tertile 1 (OR = 1.65, 95% CI 1.04, 2.62). The patterns were unrelated to hyperthyroidism or TPOAb positivity. The FOS-based confirmatory score was unrelated to thyroid function. Conclusions A diet high in fast foods, soft drinks, and legumes and low in confectionery, potatoes, butter, and jam and honey was associated with higher TSH levels in euthyroidism and higher odds of subclinical hypothyroidism.


The effect of metformin therapy on serum thyrotropin and free thyroxine concentrations in patients with type 2 diabetes: a meta-analysis
Alireza Amirabadizadeh, Atieh Amouzegar, Ladan Mehran, and Fereidoun Azizi
Springer Science and Business Media LLC
AbstractType 2 diabetes and thyroid function disorders are two common chronic endocrine disorders with the high prevalence in various populations. Metformin is well established as the first-line drug therapy for managing diabetes mellitus. In this meta-analysis, we aimed to determine the effect of metformin on serum TSH and FT4 concentrations in patients with type 2 diabetes. We searched PubMed, Scopus, web of science, Cochrane library, and google scholar to collect information on the effect of metformin on serum TSH and FT4 levels. Demographic and clinical information and serum TSH and FT4 concentrations before and after metformin treatment were extracted. Studies on patients over 18 years of age were included. A total of 11 studies including 1147 patients were selected for the final analysis. In hypothyroid patients, the TSH level decreased significantly after treatment with metformin (Hedges’s g:1.55, 95%CI 0.93–2.16, p-value < 0.001); FT4 level increased slightly after taking metformin, but the increase was not significant (Heddges’s g: − 0.30, 95%CI  − 0.90,0.31, p-value = 0.34). In euthyroid subjects, the slight decrease found in TSH and FT4 concentrations was not statistically significant. Metformin reduces TSH levels in hypothyroid patients; however, it has no effect on TSH levels in euthyroid patients. Metformin does not affect serum FT4 levels in euthyroid and hypothyroid patients.


Trajectory patterns of metabolic syndrome severity score and risk of type 2 diabetes
Atieh Amouzegar, Mohammadjavad Honarvar, Safdar Masoumi, Davood Khalili, Fereidoun Azizi, and Ladan Mehran
Springer Science and Business Media LLC
Abstract 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.


Independent association between age- and sex-specific metabolic syndrome severity score and cardiovascular disease and mortality
Mohammadjavad Honarvar, Ladan Mehran, Safdar Masoumi, Sadaf Agahi, Shayesteh Khalili, Fereidoun Azizi, and Atieh Amouzegar
Springer Science and Business Media LLC
AbstractTraditional metabolic syndrome (MetS) criteria have several limitations, which hinder its use in clinical practice. To overcome the limitations, we investigated the association between age- and sex-specific continuous MetS severity score (cMetS-S) and cardiovascular disease (CVD) and mortality beyond MetS components in the framework of the Tehran Lipid and Glucose Study. Participants aged 20–60 years at baseline were included in the study. We excluded participants with CVD, cancer, use of corticosteroids, estimated glomerular filtration rate < 30 ml/min/1.73 m2, and those who were pregnant. We evaluated the association between cMetS-S with CVD and mortality over 18 years of follow-up among 8500 participants with continuous and quantile approaches using the Cox proportional hazard regression model. In addition, the model performance of cMetS-S for predicting CVD events was compared to the conventional MetS criteria. Participants with higher cMetS-S had a significantly increased risk for CVD, coronary (CHD) and non-coronary heart disease (non-CHD), and all-cause, cardiovascular, and sudden cardiac death. Independent of the confounders and MetS components, the cMetS-S had the HRs of 1.67 (95% CI 1.47–1.89), 1.60 (95% CI 1.37–1.86), and 1.88 (95% CI 1.50, 2.35) for CVD, CHD, and non-CHD events upon 1-SD increment, respectively. The risk of mortality was increased for 1-SD of cMetS-S (all-cause mortality, HR 1.24; 95% CI 1.09–1.41; CVD mortality, HR 1.72; 95% CI 1.20–2.45; sudden cardiac death, HR 1.60; 95% CI 1.03–2.49). The model fitness of cMetS-S was superior to the conventional MetS criteria in predicting CVD and mortality. The cMetS-S provided an additional risk for CVD and mortality beyond the individual MetS components. Standardized cMetS-S could be a potential universal measure to define MetS severity while considering the weighted contribution of MetS components and their variations by age, sex, and ethnicity.


Pharmacodynamic and pharmacokinetic properties of the combined preparation of levothyroxine plus sustained- release liothyronine; a randomized controlled clinical trial
Ladan Mehran, Atieh Amouzegar, Seyed Mohsen Foroutan, Safdar Masoumi, Maryam Tohidi, Hengameh Abdi, Ali Aghaei, Amir Esmaeel Saghafinia, and Fereidoun Azizi
Springer Science and Business Media LLC
Abstract 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.


Development and validation of a continuous metabolic syndrome severity score in the Tehran Lipid and Glucose Study
Mohammadjavad Honarvar, Safdar Masoumi, Ladan Mehran, Davood Khalili, Atieh Amouzegar, and Fereidoun Azizi
Springer Science and Business Media LLC
AbstractMetabolic syndrome (MetS), defined as the coexistence of interrelated cardiometabolic risk factors, is limited by ignoring the severity of the disease and individuals with a pre-metabolic state. We aimed to develop the first age- and sex-specific continuous MetS severity score in the adult population using confirmatory factor analysis (CFA) based on the MetS components in the Middle East. Using data from the population-based Tehran Lipid and Glucose Study (TLGS) I and II datasets, we conducted CFA of the single factor MetS on 8933 adults (20–60 years old) totally, and in age and sex subgroups. We allowed for different factor loadings across the subgroups to formulate age- and sex-specific continuous MetS severity score equations. Thereafter, we validated these equations in the dataset of TLGS III participants. Triglyceride had the highest factor loading across age and sex subgroups, indicating the most correlation with MetS. Except for women aged 40–60 years, waist circumference was the second most significant factor contributing to MetS. Systolic blood pressure was more closely related to MetS in women than in men. Systolic blood pressure and fasting plasma glucose had the weakest correlation with MetS among the 40–60 age group. Moreover, as women age, the contribution of fasting plasma glucose to MetS tended to decline, while it remained relatively constant in men. The resulting MetS severity score was correlated with age and homeostasis model assessment of insulin resistance. Furthermore, the continuous MetS severity score well predicted the traditional MetS according to receiver operating characteristic analysis in the validation dataset. The age- and sex-specific continuous MetS severity score for the West Asian adult population provides a tangible quantitative measure of MetS enabling clinicians to screen and monitor the individuals at risk and assess their metabolic trends.


Assessing the Risk of Cardiovascular Diseases: Metabolic Syndrome Versus Quantitative Metabolic Syndrome Severity Score




Sex-specific Trajectories of Insulin Resistance Markers and Reduced Renal Function During 18 Years of Follow-up: TLGS
Atieh Amouzegar, Mohammadjavad Honarvar, Safdar Masoumi, Maryam Tohidi, Ladan Mehran, and Fereidoun Azizi
The Endocrine Society
Abstract Context The evidence suggest that insulin resistance (IR) complicates chronic kidney disease (CKD); however, the longitudinal association of IR with development of CKD is unknown. Objective This work aimed to investigate the association between the dynamic course of insulin resistance and CKD. Methods In the longitudinal, population-based Tehran Lipid and Glucose Study, 3071 eligible participants aged 20 years or older were followed for 18 years at 3-year intervals. Homeostatic model assessment of insulin resistance (HOMA-IR) and clinical surrogate markers of IR, including triglyceride-glucose index (TyG), visceral adiposity index (VAI), and lipid accumulation product (LAP), were calculated. Using latent variable mixture modeling, sex-specific trajectories were plotted for each IR marker. Trajectory group association of the IR markers with CKD was determined using the multivariable Cox proportional-hazards regression model. Results For HOMA-IR, 2 distinct trajectory patterns (stable and increasing), and for TyG, VAI, and LAP, 3 trajectories (low, moderate, and high) were identified. The participants with an increasing HOMA-IR trajectory had a significantly increased risk of CKD in men (hazard ratio [HR]: 1.72; 95% CI, 1.06-2.79) and women (HR: 1.37; 95% CI, 1.00-1.89) after adjusting for confounding variables. The high TyG and VAI trajectory classes were associated with a higher risk of CKD than the low TyG and VAI trajectory classes both in men (TyG: HR: 1.97; 95% CI, 1.12-3.46; VAI: HR:1.66; 95% CI, 1.06-2.62) and women (TyG: HR: 1.50; 95% CI, 1.06-2.12; VAI: HR:1.66; 95% CI, 1.20-2.31). In contrast, the high LAP (HR: 3.38; 95% CI, 2.08-5.48) trajectory was associated with incident CKD only in women. Conclusion An increasing trend of HOMA-IR is associated with a higher risk of CKD in men and women. Among clinical IR surrogate markers, abnormal trajectory patterns of LAP in women and TyG and VAI in both sexes are associated with a higher risk of CKD.


Long-Term Follow-up of Graves Orbitopathy After Treatment With Short- or Long-Term Methimazole or Radioactive Iodine
Fereidoun Azizi, Hengameh Abdi, Ladan Mehran, Petros Perros, Safdar Masoumi, and Atieh Amouzegar
Elsevier BV



The impact of metabolic syndrome on chronic kidney disease development. Insights from a big prospective study
Seyedeh Melika Fanaei, Ladan Mehran, Atieh Amouzegar, Safdar Masoumi, Atefeh Amouzegar, and Freidoun Azizi
Wiley
BACKGROUND Chronic kidney disease (CKD) can progress over time and cause renal replacement therapy. Studies showed an association between metabolic syndrome (MetS) and CKD. Current evidence is from cross sectional studies. There is a need for 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, use of corticosteroid, 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+) (5) MetS+ (DM-, HTN-). RESULT At baseline the mean age of the participants was 39.8±13.3 y; 4996 (55.6%) were females. CKD was developed in 2,038 (22.7 %) subjects during 18 years of follow-up, of whom 1,107 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 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 chronic kidney disease incidence at long term follow-up. Hypertension, diabetes and age were strong indicators, while abdominal obesity and reduced HDL were not associated with the incidence of CKD.


Association of trajectory of body shape index with all-cause and cause-specific mortality: 18 years follow-up
Elham Kazemian, Ladan Mehran, Safdar Masoumi, Atieh Amouzegar, and Fereidoun Azizi
Frontiers Media SA
ObjectivesThe current study aimed to examine how the trajectory of a body shape index (ABSI) could predict mortality in a prospective cohort of 5587 participants.MethodsA Growth Mixture Model (GMM) was employed to identify ABSI and body shape trajectories spanning from 2000 to 2018. Multivariate Cox regression models with hazard ratio (HR) and 95% confidence intervals (CIs) were built to assess the association of death from all-cause and cardiovascular disease (CVD) with ABSI and body shape trajectories.ResultsWe found that individuals with a low ABSI–marked increase (Class II) and high ABSI–marked increase trajectory (Class III) had a higher risk of all-cause (adjusted HR for Class II, 1.37; 95%CI, 1.04-1.79; adjusted HR for Class III, 1.42; 95%CI, 1.05-1.91) and non- CVD mortality (adjusted HR for Class II, 1.38; 95%CI, 1.00-1.91; adjusted HR for Class III, 1.42; 95%CI, 1.00-2.05) as well as an increased risk of CVD (adjusted HR for Class II, 1.40; 95%CI, 1.14-1.71; adjusted HR for Class III, 1.42; 95%CI, 1.13-1.78) and coronary heart disease (CHD) (adjusted HR for Class II, 1.52; 95%CI, 1.18-1.96; adjusted HR for Class III, 1.47; 95%CI, 1.11-1.95. The trajectories of body shape phenotypes did not show any significant associations with mortality, CVD, or CHD events.ConclusionsABSI trajectories might be associated with subsequent risk of mortality and CVD events.


Weight fluctuation, mortality, and cardiovascular disease in adults in 18 years of follow-up: Tehran Lipid and Glucose Study
L. Mehran, M. Honarvar, S. Masoumi, D. Khalili, A. Amouzegar, and F. Azizi
Springer Science and Business Media LLC



Efficacy and Safety of Long-Term Methimazole versus Radioactive Iodine in the Treatment of Toxic Multinodular Goiter
Fereidoun Azizi, Navid Saadat, Mir Alireza Takyar, Hengameh Abdi, Ladan Mehran, and Atieh Amouzegar
Korean Endocrine Society
Background: This study compared the degree of sustained control of hyperthyroidism in patients with toxic multinodular goiter (TMNG) treated with long-term methimazole (LT-MMI) or radioactive iodine (RAI).Methods: In this clinical trial, 130 untreated patients with TMNG were randomized to either LT-MMI or RAI treatment. Both groups were followed for 108 to 148 months, with median follow-up durations of 120 and 132 months in the LT-MMI and RAI groups, respectively. Both groups of patients were followed every 1 to 3 months in the first year and every 6 months thereafter.Results: After excluding patients in whom the treatment modality was changed and those who were lost to follow-up, 53 patients in the LT-MMI group and 54 in the RAI group completed the study. At the end of the study period, 50 (96%) and 25 (46%) patients were euthyroid, and two (4%) and 25 (46%) were hypothyroid in LT-MMI and RAI groups, respectively. In the RAI group, four (8%) patients had subclinical hyperthyroidism. The mean time to euthyroidism was 4.3±1.3 months in LT-MMI patients and 16.3± 15.0 months in RAI recipients (<i>P</i><0.001). Patients treated with LT-MMI spent 95.8%±5.9% of the 12-year study period in a euthyroid state, whereas this proportion was 72.4%±14.8% in the RAI-treated patients (<i>P</i><0.001). No major treatment-related adverse events were observed in either group.Conclusion: In patients with TMNG, LT-MMI therapy is superior to RAI treatment, as shown by the earlier achievement of euthyroidism and the longer duration of sustained normal serum thyrotropin.


BMI variability and incident diabetes mellitus, Tehran Lipid and Glucose Study (TLGS)
Ladan Mehran, Pouria Mousapour, Davood Khalili, Leila Cheraghi, Mohammadjavad Honarvar, Atieh Amouzegar, and Fereidoun Azizi
Springer Science and Business Media LLC
AbstractPrevious epidemiologic studies debated the association of body mass index (BMI) trends with cardiovascular disease and mortality. This study aimed to evaluate the association of BMI variability and slope with the incidence of Type 2 diabetes mellitus (T2DM) in a sex-stratified 15.8-year follow-up in the population-based Tehran Lipid and Glucose Study (TLGS). Of 10,911 individuals aged 20–60 years, 4981 subjects were included and followed for 15.8-years. The slope coefficient of BMI in the linear regression model represented individuals’ BMI trends up to the incidence of DM. The root mean squared error (RMSE) of the BMI linear trend was selected to reflect BMI variability through six follow-ups. Cox proportional hazards regression was used to investigate the association of the baseline BMI, BMI slope and RMSE with the incidence of T2DM among men and women. Multivariable-adjusted HRs of T2DM for each SD increment in BMI slope was 1.18 (95% CI: 0.94–1.48, p = 0.161) in normal weight men and 1.26 (95% CI: 1.10–1.44, p = 0.001) in overweight and obese men. However, in women, each SD increment in BMI slope increased the risk of T2DM with a HR of 1.19 (95% CI: 1.01–1.40, p = 0.039) in normal weight, and 1.14 (95% CI: 1.08–1.19, p < 0.001) in women with BMI ≥ 25 kg/m2. In men with a baseline BMI ≥ 25 kg/m2, BMI-RMSE was associated with a decreased risk of T2DM (HR: 0.71, 95% CI: 0.53–0.93, p = 0.015). Baseline BMI was not associated with the risk of diabetes in men and women. Positive BMI slope is associated with the development of diabetes in both sexes. The association of BMI variability with incident T2DM differs according to sex and baseline BMI. BMI variability is associated with a lower risk of T2DM in overweight and obese men. BMI variability in women and baseline BMI in both gender are not related to the risk of T2DM.


Natural history of subclinical hypothyroidism and prognostic factors for the development of overt hypothyroidism: Tehran Thyroid Study (TTS)
A. Amouzegar, M. Dehghani, H. Abdi, L. Mehran, S. Masoumi, and F. Azizi
Springer Science and Business Media LLC



Time to Normalization and Sustainable Normal Serum Thyrotropin Concentrations in Patients with Hyperthyroidism: Comparison of Methimazole and Radioactive Iodine Treatments
Fereidoun Azizi, Navid Saadat, Hengameh Abdi, Ladan Mehran, Safdar Masoumi, Mir Alireza Takyar, and Atieh Amouzegar
Elsevier BV



Appropriate duration of antithyroid drug treatment as a predictor for relapse of Graves’ disease: a systematic scoping review
F. Azizi, H. Abdi, L. Mehran, and A. Amouzegar
Springer Science and Business Media LLC
Following the conventional 12–18 month antithyroid drug (ATD) treatment in Graves’ disease (GD), 50% of patients experience relapse of hyperthyroidism. The aim of this systematic scoping review was critical appraisal of duration of ATD therapy in the last 80 years. Articles were identified through the search of PubMed from January 1, 1941 to April 30, 2021. All study types were included. Articles were eligible if they reported data on the length of ATD treatment, particularly thyroid hormones and TSH receptor antibodies (TRAb) concentrations and specifically those with data on the remission and/or relapse rates. We described major progress regarding the duration of ATD therapy and related outcomes at every 20 years. Articles of 1941–1960 were mainly concerned with determination of favorable treatment, minimal effective dose, side effects and rate of remission after < 12-month ATD therapy. Studies with larger number of patients and longer follow-ups appeared in 1961–1980; higher remission rate after 18–24 months versus 6 months of ATD therapy was reported. Articles of 1981–2000 focused on identification of factors associated with high relapse rates after discontinuation of ATD. In 2001–2021, ATD became the first choice of treatment in many countries. However, 12–18 months of ATD therapy was arbitrarily chosen as the appropriate option. According to recent studies, persistent normalization of TRAb occurs after 5 years of methimazole therapy and ATD treatment of > 60 months could offer a 4-year remission rate of 85%. Long-term ATD treatment for more than 60 months is safe and effective, has the highest remission rate and cures most patients with GD; hence, it should be considered as the most appropriate duration for ATD therapy in these patients.

RECENT SCHOLAR PUBLICATIONS

Treatment of Primary Hypothyroidism by Slow-Release Liothyronine Monotherapy
F Azizi, A Amouzegar, H Abdi, S Masoumi, L Mehran
Endocrine, Metabolic & Immune Disorders-Drug Targets 2025



Optimal Cut-off Points of the Standardized Continuous Metabolic Syndrome Severity Score (cMetS-S) for Predicting Cardiovascular Disease (CVD) and CVD Mortality in the Tehran
M Adib, L Mehran, S Masoumi, I Vatanpoor, F Azizi, A Amouzegar
International Journal of Endocrinology and Metabolism 22 (4), e154255 2024



Association between changes in thyroid hormones and incident type 2 diabetes using joint models of longitudinal and time-to-event data: more than a decade follow up in the
A Amirabadizadeh, L Mehran, A Amouzegar, S Asgari, D Khalili, F Azizi
Frontiers in Endocrinology 15, 1475286 2024



Association between body mass index trajectories and type 2 diabetes incidence over an 18-year follow-up in the Tehran Lipid and Glucose Study
N Hassanloo, L Mehran, A Amouzegar, H Abdi, S Masoumi, F Azizi, ...
Scientific Reports 14 (1), 27615 2024



Approach to the patient considering long-term antithyroid drug therapy for Graves’ disease
F Azizi, L Mehran, H Abdi, A Amouzegar
The Journal of Clinical Endocrinology & Metabolism 109 (10), e1881-e1888 2024



Independent association of metabolic syndrome severity score and risk of diabetes: findings from 18 years of follow-up in the Tehran Lipid and Glucose Study
A Amouzegar, M Honarvar, S Masoumi, S Agahi, F Azizi, L Mehran
BMJ open 14 (9), e078701 2024



Association between maternal hypothyroidism, baby birth weight, and adult cardiovascular disease risk: insights from ECG measurements
MA Mirshekar, L Mehran, FF Shahrivar
International Journal of Clinical and Experimental Pathology 17 (8), 257 2024



Interrelationship between thyroid hormones and reduced renal function, a review article
S Agahi, A Amouzegar, M Honarvar, F Azizi, L Mehran
Thyroid Research 17 (1), 14 2024



The association of body mass index variability with cardiovascular disease and mortality: a mediation analysis of pooled cohorts
L Mehran, M Honarvar, S Masoumi, D Khalili, F Azizi, MJ Blaha, ...
Frontiers in Endocrinology 15, 1345781 2024



Vitamin D and Anti-thyroid Peroxidase Antibody: Tehran Thyroid Study
FS Saeidian, F Sarvghadi, A Amouzegar, L Mehran, S Mahdavi, ...
Iranian Journal of Endocrinology and Metabolism 25 (6), 468-477 2024



Cardiometabolic-related dietary patterns and thyroid function: a population-based cross-sectional study
N Moslehi, S Mohammadpour, P Mirmiran, L Mehran, F Azizi
European Journal of Medical Research 28 (1), 602 2023



Association of trajectory of body shape index with all-cause and cause-specific mortality: 18 years follow-up
E Kazemian, L Mehran, S Masoumi, A Amouzegar, F Azizi
Frontiers in endocrinology 14, 1259849 2023



Assessing the Risk of Cardiovascular Diseases: Metabolic Syndrome Versus Quantitative Metabolic Syndrome Severity Score
M Adib, L Mehran, MJ Honarvar, S Masoumi, F Azizi, A Amouzegar
Iranian Journal of Endocrinology and Metabolism 25 (4), 339-350 2023



The effect of metformin therapy on serum thyrotropin and free thyroxine concentrations in patients with type 2 diabetes: a meta-analysis
A Amirabadizadeh, A Amouzegar, L Mehran, F Azizi
Scientific Reports 13 (1), 18757 2023



Trajectory patterns of metabolic syndrome severity score and risk of type 2 diabetes
A Amouzegar, M Honarvar, S Masoumi, D Khalili, F Azizi, L Mehran
Journal of Translational Medicine 21 (1), 750 2023



Independent association between age-and sex-specific metabolic syndrome severity score and cardiovascular disease and mortality
M Honarvar, L Mehran, S Masoumi, S Agahi, S Khalili, F Azizi, ...
Scientific Reports 13 (1), 14621 2023



Pharmacodynamic and pharmacokinetic properties of the combined preparation of levothyroxine plus sustained-release liothyronine; a randomized controlled clinical trial
L Mehran, A Amouzegar, SM Foroutan, S Masoumi, M Tohidi, H Abdi, ...
BMC Endocrine Disorders 23 (1), 182 2023



Sex-specific trajectories of insulin resistance markers and reduced renal function during 18 years of follow-up: TLGS
A Amouzegar, M Honarvar, S Masoumi, M Tohidi, L Mehran, F Azizi
The Journal of Clinical Endocrinology & Metabolism 108 (6), e230-e239 2023



Development and validation of a continuous metabolic syndrome severity score in the Tehran Lipid and Glucose Study
M Honarvar, S Masoumi, L Mehran, D Khalili, A Amouzegar, F Azizi
Scientific Reports 13 (1), 7529 2023



Long-term follow-up of graves orbitopathy after treatment with short-or long-term methimazole or radioactive iodine
F Azizi, H Abdi, L Mehran, P Perros, S Masoumi, A Amouzegar
Endocrine Practice 29 (4), 240-246 2023

MOST CITED SCHOLAR PUBLICATIONS

Serum free thyroxine concentration is associated with metabolic syndrome in euthyroid subjects
L Mehran, A Amouzegar, M Tohidi, M Moayedi, F Azizi
Thyroid 24 (11), 1566-1574 2014
Citations: 135



Thyroid function and metabolic syndrome: a population-based thyroid study
L Mehran, A Amouzegar, PK Rahimabad, M Tohidi, Z Tahmasebinejad, ...
Hormone and Metabolic Research 49 (03), 192-200 2017
Citations: 96



The prevalence, incidence and natural course of positive antithyroperoxidase antibodies in a population-based study: Tehran thyroid study
A Amouzegar, S Gharibzadeh, E Kazemian, L Mehran, M Tohidi, F Azizi
PloS one 12 (1), e0169283 2017
Citations: 95



Sustainability of a well-monitored salt iodization program in Iran: marked reduction in goiter prevalence and eventual normalization of urinary iodine concentrations without
F Azizi, L Mehran, R Sheikholeslam, A Ordookhani, M Naghavi, ...
Journal of endocrinological investigation 31, 422-431 2008
Citations: 94



Experiences in the prevention, control and elimination of iodine deficiency disorders: a regional perspective
F Azizi, L Mehran
East Mediterr Health J 10 (6), 761-70 2004
Citations: 83



Establishment of the trimester-specific reference range for free thyroxine index
F Azizi, L Mehran, A Amouzegar, H Delshad, M Tohidi, S Askari, ...
Thyroid 23 (3), 354-359 2013
Citations: 74



Eighteen years of continuously sustained elimination of iodine deficiency in the Islamic Republic of Iran: the vitality of periodic monitoring
H Delshad, A Amouzegar, P Mirmiran, L Mehran, F Azizi
Thyroid 22 (4), 415-421 2012
Citations: 70



Reduced sensitivity to thyroid hormone is associated with diabetes and hypertension
L Mehran, N Delbari, A Amouzegar, M Hasheminia, M Tohidi, F Azizi
The Journal of Clinical Endocrinology & Metabolism 107 (1), 167-176 2022
Citations: 69



Reference limit of thyrotropin (TSH) and free thyroxine (FT₄) in thyroperoxidase positive and negative subjects: A population based study
A Amouzegar, H Delshad, L Mehran, M Tohidi, F Khafaji, F Azizi
Journal of endocrinological investigation 36 (11), 950-954 2013
Citations: 68



Worldwide recall rate in newborn screening programs for congenital hypothyroidism
L Mehran, D Khalili, S Yarahmadi, A Amouzegar, M Mojarrad, N Ajang, ...
International journal of endocrinology and metabolism 15 (3), e55451 2017
Citations: 55



Trimester‐Specific Reference Ranges for Thyroid Hormones in Iranian Pregnant Women
L Mehran, A Amouzegar, H Delshad, S Askari, M Hedayati, G Amirshekari, ...
Journal of thyroid research 2013 (1), 651517 2013
Citations: 54



Investigating the prevalence of primary thyroid dysfunction in obese and overweight individuals: Tehran thyroid study
M Mahdavi, A Amouzegar, L Mehran, E Madreseh, M Tohidi, F Azizi
BMC Endocrine Disorders 21 (1), 89 2021
Citations: 52



Thyroid disease and the metabolic syndrome
L Mehran, A Amouzegar, F Azizi
Current Opinion in Endocrinology, Diabetes and Obesity 26 (5), 256-265 2019
Citations: 51



Association between thyroid function and body mass index: a 10-year follow-up
H Abdi, E Kazemian, S Gharibzadeh, A Amouzegar, L Mehran, M Tohidi, ...
Annals of Nutrition and Metabolism 70 (4), 338-345 2017
Citations: 50



Variations in serum free thyroxine concentration within the reference range predicts the incidence of metabolic syndrome in non-obese adults: a cohort study
L Mehran, A Amouzegar, M Bakhtiyari, MA Mansournia, PK Rahimabad, ...
Thyroid 27 (7), 886-893 2017
Citations: 49



Natural course of thyroid disease profile in a population in nutrition transition: Tehran Thyroid Study
F Azizi, A Amouzegar, H Delshad, M Tohidi, L Mehran, Y Mehrabi
Archives of Iranian medicine 16 (7), 0-0 2013
Citations: 47



The association of cigarette smoking with serum TSH concentration and thyroperoxidase antibody
L Mehran, A Amouzgar, H Delshad, F Azizi
Experimental and clinical endocrinology & diabetes 120 (02), 80-83 2012
Citations: 46



Management of thyroid peroxidase antibody euthyroid women in pregnancy: comparison of the american thyroid association and the endocrine society guidelines
L Mehran, M Tohidi, F Sarvghadi, H Delshad, A Amouzegar, OP Soldin, ...
Journal of thyroid research 2013 (1), 542692 2013
Citations: 43



Association between thyroid hormones, thyroid antibodies and insulin resistance in euthyroid individuals: A population-based cohort
A Amouzegar, E Kazemian, S Gharibzadeh, L Mehran, M Tohidi, F Azizi
Diabetes & metabolism 41 (6), 480-488 2015
Citations: 42



Screening and management of hypothyroidism in pregnancy: results of an Asian survey
F Azizi, A Amouzegar, L Mehran, S Alamdari, I Subekti, B Vaidya, ...
Endocrine Journal 61 (7), 697-704 2014
Citations: 41