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Background: The contribution of high-density lipoprotein cholesterol (HDL-C) subclasses to incident cardiovascular disease (CVD) and coronary heart disease (CHD) remains a subject of debate., Objectives: The objective of this study was to investigate these associations in a population with a high prevalence of dyslipidemia and CVD., Methods: In a nested case-control study, HDL-C and its subclasses (HDL2-C and HDL3-C) in 370 age and gender-matched case and control subjects were determined. This study employed multivariable-adjusted conditional logistic regression to calculate the odds ratios (ORs) for the associations between HDL-C, HDL2-C, HDL3-C, and HDL2-C/HDL3-C (both as continuous and categorical variables) with incident CVD and CHD. The present study models were adjusted for a comprehensive set of confounders, including body mass index, current smoking, hypertension, type 2 diabetes mellitus, use of lipid-lowering drugs, family history of premature CVD, non-HDL-C, and triglycerides., Results: In multivariate analysis, when considering lipoprotein parameters as continuous variables, a 1-unit increase in HDL-C and HDL3-C was associated with a reduced risk of incident CVD and CHD. For CVD, the ORs (95% confidence intervals [CI]) were 0.95 (0.92 - 0.98) and 0.95 (0.93 - 0.98) for HDL-C and HDL3-C, respectively. The corresponding values for CHD were 0.94 (0.91 - 0.97) and 0.94 (0.91 - 0.97). In the categorical approach to lipoprotein parameters, higher quartiles of HDL-C and HDL3-C, compared to the first quartile, were significantly associated with a lower risk of incident CVD and CHD. The ORs (95% CI) for the fourth quartiles were 0.43 (0.25 - 0.74, P for trend = 0.003) and 0.46 (0.27 - 0.78, P for trend = 0.005) for HDL-C and HDL3-C regarding CVD and 0.32 (0.17 - 0.59) and 0.32 (0.18 - 0.59) (all P for trend = 0.001) regarding CHD, respectively. Paradoxically, across quartiles of HDL2-C/HDL3-C, this lipid ratio was associated with a higher risk of CHD (92% higher risk in the fourth quartile)., Conclusions: The results showed that HDL3-C, but not HDL2-C, was primarily responsible for the protective effect of HDL-C against CVD, particularly CHD, in Iranian adults., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023, Chary et al.)

Background: Male infertility is a growing health problem. It is proposed that infertility is associated with some metabolic abnormalities., Objectives: This study aimed to examine the prevalence of self-reported male infertility and related metabolic disturbances., Methods: This is a cross-sectional analysis of the Tehran Lipid and Glucose Study (TLGS). A total of 1526 males participated in the study. Logistic regression was used to examine metabolic factors associated with self-reported male infertility., Results: The total prevalence of self-reported male infertility was 6.42%. The mean (SD) body mass index (BMI) of participants among fertile and infertile males was 26.80 (3.93) and 26.92 (4.36), respectively. The majority of participants in both groups were in the age group of 40-50 years old. In the fully adjusted model, the odds of infertility were significantly increased by each unit increase in total cholesterol [TC; odds ratio (OR), 1.01; 95% CI, 1.01 - 1.01; P = 0.03] and hip circumference (HC; OR, 1.06; 95% CI, 1.00 - 1.12; P = 0.02), respectively., Conclusions: The prevalence of self-reported male infertility was 6.42%. Male infertility was positively associated with TC and HC, indicating that knowledge about these risks might assist health care professionals and governments in developing and executing measures to change the status quo., Competing Interests: Conflict of Interests: Dr. Ramezani Tehrani has nothing to disclose., (Copyright © 2023, International Journal of Endocrinology and Metabolism.)

Context: Findings from studies evaluating adverse pregnancy outcomes in pregnant women with subclinical hyperthyroidism are conflicting and inconclusive., Objectives: In this systematic review and meta-analysis, our aim was to evaluate the pooled odds ratio (OR) of adverse pregnancy outcomes in women with subclinical hyperthyroidism, compared to euthyroid women., Data Sources: Scopus, PubMed (including Medline), and Web of Science databases were systemically searched for regaining published studies to January 2022 examining adverse pregnancy outcomes in women with subclinical hyperthyroidism., Study Selection: Outcomes of interest were classified into seven composite outcomes, including hypertensive disorders, preterm delivery, macrosomia/large for gestational age (LGA), pregnancy loss, adverse maternal outcomes, adverse neonatal outcomes, and adverse fetal outcomes., Data Extraction: In this meta-analysis, both fixed and random effect models were used. Publication bias was also evaluated by Egger test and the funnel plot, and the trim and fill method was conducted in case of a significant result, to adjust the bias., Results: Of 202 records retrieved through searching databases, 11 studies were selected for the final analyses. There were no significant differences in pooled ORs of hypertensive disorders, preterm delivery, macrosomia/LGA, and pregnancy loss in pregnant women with subclinical hyperthyroidism, compared to the euthyroid controls. The pooled OR of adverse maternal, neonatal, and fetal outcomes in pregnant women with subclinical hyperthyroidism was not statistically significantly different from that of the euthyroid control group., Conclusions: The current meta-analysis demonstrated that subclinical hyperthyroidism in pregnancy is not related with adverse maternal and fetal outcomes. Therefore, clinicians should be avoided unnecessary treatments for pregnant women with subclinical hyperthyroidism., Competing Interests: Conflict of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022, International Journal of Endocrinology and Metabolism.)

Background: Body image is known as an important factor affecting different aspects of adolescents' health; however, its relationship with lifestyle, body mass index (BMI), and health-related quality of life (HRQoL) in Iranian adolescents has not been addressed in a conceptual model., Objectives: This study aimed to investigate the network associations among body image, lifestyle, BMI, and HRQoL in adolescent boys and girls., Methods: The present study examined 760 adolescents (15 - 18 years) from Tehran. Adolescents reported their weight and height, according to which the participants' BMIs were calculated. The adolescents' body image, lifestyle, and HRQoL were assessed using a set of questionnaires, including the Body Image Scale for Youth (BISY), Modifiable Activity Questionnaire (MAQ), Eating Habits Checklist, Eating Attitudes Test (EAT-26), and Pediatric Quality of Life Inventory (PedsQL TM )., Results: The participants' mean age and BMI were 16.5 ± 1.0 years and 22.4 ± 4.6 kg/m 2 , respectively. More than one-third of boys (39.9%) and less than a quarter of girls (22.6%) were overweight/obese. In the final model, body image was significantly and directly associated with physical activity, disordered eating, eating habits, and HRQoL in both genders (P < 0.05). Moreover, body image was directly correlated with screen time in boys (P = 0.012) and BMI in girls (P = 0.001). Body image was indirectly correlated with BMI by the mediating role of disordered eating in girls. Moreover, body image was indirectly associated with HRQoL by the mediating role of physical activity and eating habits in both genders and screen time only in boys., Conclusions: The network associations among body image, lifestyle, BMI, and HRQoL revealed a gender-specific pattern among the study population. Body image was a significant determinant of lifestyle and HRQoL in both genders and excessive weight in girls. The present findings would contribute to designing and implementing relevant health promotion interventions., Competing Interests: Conflict of Interests: Nothing to disclose., (Copyright © 2022, International Journal of Endocrinology and Metabolism.)

Background: Maternal characteristics have been known to be associated with parenting practices, which could eventually influence their child's weight and health-related quality of life (HRQoL)., Objectives: This study aimed to assess the direct and indirect associations of maternal emotional states (depression, anxiety, and stress) with body mass index (BMI) and HRQoL in their children., Methods: This study was conducted within the framework of the Tehran lipid and glucose study (TLGS). Participants were the children (n = 231) enrolled in TLGS during 2014 - 2016, who had complete data on maternal emotional states. The body weight and height of children were measured using the standard protocol, and BMI Z-score was determined using Anthroplus. Also, HRQoL in children and emotional states in mothers were assessed using the Iranian version of the pediatric quality of life inventory (PedsQLTM4.0) and the depression, anxiety, and stress scale (DASS-21), respectively. Structural equations modeling (SEM) was used to assess the direct and indirect relations of maternal emotional states with children's BMI Z-score and HRQoL., Results: Mean age, BMI Z-score, and HRQoL total score in children were 13.8 ± 3.1 years, 0.74 ± 1.5, and 84.7 ± 11.3, respectively. In the mothers, median DASS-21 scores (interquartile ranges) in the three scales of depression, anxiety, and stress were 4 (0 - 10), 6 (2 - 12), and 14 (8 - 20), respectively. Maternal level of education was significantly associated with the DASS-21 score (β = -0.23, 95% CI: -0.37,-0.07). Maternal DASS-21 score was significantly associated with BMI Z-score only in girls (β = 0.25, 95% CI: 0.06, 0.53). Significant determinants of HRQoL in boys were the child's age (β = -0.21, 95% CI: -0.40, -0.01) and maternal education (β = -0.24, 95%CI: -0.44, -0.02) and emotional state (β = -0.24, 95% CI: -0.44, -0.03). The child's age (β = -0.33, 95% CI: -0.53, -0.10) and maternal emotional state (β = -0.31, 95% CI: -0.54, -0.08) were significantly associated with HRQoL in girls., Conclusions: The maternal emotional state is an important determinant of HRQoL in children, regardless of their weight status. Further research is recommended to examine the current hypothesized model in rural and suburban populations, taking into consideration more influential factors., Competing Interests: Conflict of Interests: The authors declare that they have no competing interests., (Copyright © 2021, International Journal of Endocrinology and Metabolism.)

Background: Following menopause, the risk of many diseases is increased, and this situation may be due to changes in anthropometric indices (AI), while the association between adiposity and age at natural menopause (ANM) is not clear yet., Objectives: This longitudinal study was conducted to investigate the ability of AI in predicting ANM., Methods: For this purpose, a total of 3,876 women aged > 20 years old from participants of the Tehran lipid and glucose study (TLGS) met our eligibility criteria. The association between ANM and various AIs was assessed using the Accelerated Failure Time (AFT) model, and time ratio (TR) with 95% confidence intervals was reported in this longitudinal study., Results: The median [interquartile range (IQR) 25 - 75] of the survival time was 12.5 (7.9 - 15.8) years. At the end of the follow-up, 1,479 (38.2%) of the participants reached menopause. The median time to natural menopause was decreased by about 2% with one standard deviation (SD) increase of both a body shape index (ABSI) (time ratio (TR): 0.98, 95% CI: 0.97, 0.99) and lipid accumulation product (LAP) (TR: 0.98, 95% CI: 0.98, 0.99) z-scores; and this time was increased by about 1% (TR: 1.01, 95% CI: 1.00, 1.02) with one SD increase in body mass index (BMI) z-score., Conclusions: The ABSI, LAP, and BMI were the most useful AIs for identification of the time to menopause onset, and ABSI and LAP were inversely associated with the ANM. Also, the BMI was directly associated with the ANM., Competing Interests: Conflict of Interests: The authors declare that there is no conflict of interest., (Copyright © 2021, International Journal of Endocrinology and Metabolism.)

Background: Further studies are needed to extend our knowledge about the association between male infertility and cardio-metabolic disorders., Objectives: We aimed to assess the association between male infertility and cardiometabolic disturbances using a population-based design., Methods: In total, 1611 participants of the Tehran-Lipid and Glucose-Study (phase III) were categorized into two groups of men with documented male infertility (n = 88) and those with at least one live birth and no history of primary infertility (n = 1523). Logistic regression was applied to explore the association between male infertility and cardiometabolic disturbances, including diabetes mellitus, pre-diabetes, hypertension, metabolic syndrome, dyslipidemia, obesity, central obesity, and chronic kidney disease, following adjustment for age and body mass index (BMI)., Results: The unadjusted model revealed a significant association between infertility and hypertension and CKD (OR = 1.8; 95% CI: 1.2, 2.9, P-value = 0.006 and OR = 1.9; 95% CI: 1.1, 3.6, P-value = 0.033), respectively. However, after adjusting for age and BMI, as potential confounders, this association was not significant. Moreover, there was no association between infertility and other cardiometabolic disturbances, including diabetes and pre-diabetes, metabolic syndrome, dyslipidemia, obesity, and central obesity in both unadjusted and adjusted models., Conclusions: Our study revealed no association between male infertility and cardiometabolic disturbances. The findings can pave the way for further studies to extend our knowledge in this field. More population-based studies with a large sample size are warranted to confirm these findings., Competing Interests: Conflict of Interests: There is no conflict of interest., (Copyright © 2021, International Journal of Endocrinology and Metabolism.)

Background: Nitric oxide (NO) plays a key role in thyroid function regulation through the inhibition of iodide (I) uptake at the thyroidal sodium-iodide symporter (NIS) and impacts on the thyroid vascularity and blood flow., Objectives: This study aimed to evaluate the association between serum NO metabolites (NOx) and thyroid-stimulating hormone (TSH), free thyroxin (FT4), and anti-thyroid peroxidase (TPOAb) changes. Also, it aimed at evaluating the correlation between serum NOx and the incidence of clinical hypothyroidism, characterized by elevated TSH level and decreased FT4 concentration, and subclinical hypothyroidism, characterized by mildly elevated TSH level despite FT4 concentration within the normal range, over three years of follow-up., Methods: This study included 1,137 participants of the Tehran Thyroid study (TTS), aged > 20 years old, for whom data on serum TSH, FT4, and TPOAb in the third and fourth phases, and serum NOx in the third phase were available. Changes in TSH (ΔTSH), FT4 (ΔFT4), and TPOAb (ΔTPO) between the third and fourth phases were calculated, and the associations between serum NOx and ΔTSH, ΔFT4, and ΔTPOAb were assessed after multivariable adjustment using linear regression analysis., Results: No significant association was found between serum NOx and ΔTSH, ΔFT4, and ΔTPOAb after the multivariable adjustment; neither was any observed in TPOAb split groups after multivariable adjustment. No significant association was found between serum NOx tertiles and clinical and subclinical hypothyroidism incidence in the fourth phase of TTS., Conclusions: There was no association between serum NOx levels and changes in TSH, FT4, and TPOAb and clinical and subclinical hypothyroidism incidence., Competing Interests: Conflict of Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article., (Copyright © 2021, International Journal of Endocrinology and Metabolism.)

Background: Chronic kidney disease (CKD) is a rising public health concern that has detrimental effects on cardiovascular health and overall survival. Subclinical hypothyroidism (SCH) has been associated with poor outcomes in the general population. It is thought to be more prevalent in CKD subjects, and their coexistence may contribute to poor outcomes in these patients. We aimed to determine the prevalence of SCH in CKD., Methods: Using data from the Tehran thyroid study, which is a prospective population-based cohort study, adult subjects with an estimated Glomerular Filtration Rate (eGFR) of 60 mL/min/1.73 m 2 or less were selected for studying the prevalence of thyroid abnormalities, as well as other known cardiovascular risk factors., Results: Of 5,626 subjects recruited, 823 (14.6%) individuals had CKD. Individuals with CKD were older, heavier, had a higher prevalence of diabetes, higher serum thyrotropin, and thyroid peroxidase anti-body levels, but lower free thyroxine levels. The prevalence of SCH was 7.3% and 5.2% (P < 0.001) in kidney disease and non-kidney disease subjects, respectively. However, there was no difference in the risk of SCH between CKD and non-CKD subjects after adjustment for age, sex, BMI, smoking, and TPOAb (OR: 1.28; 95%CI, 0.89 - 1.83). None of the metabolic markers compared between the CKD subgroups of those with and without SCH remained statistically significantly different after adjusting for age and gender., Conclusions: The prevalence of SCH was not higher in CKD after controlling for confounding factors. Besides, CKD subjects with and without SCH had no different metabolic parameters., Competing Interests: Conflict of Interests: There is no conflict of interest., (Copyright © 2021, International Journal of Endocrinology and Metabolism.)

Background: Von Hippel Lindau (VHL) disease is a hereditary disorder characterized by the development of benign or malignant tumors in the brain, spinal cord, eyes, adrenal medulla, kidney, pancreas, and many other organs. Advances in molecular diagnosis have led to the identification of the affected members of families at earlier stages. We present the clinical, laboratory, and genetic characteristics of five generations of a large Iranian kindred with VHL., Methods: The proband, a 52-year-old Iranian man, was recognized with VHL. All family members underwent clinical, laboratory, imaging, and genetic evaluation. Medical files and histopathology reports of patients who had been operated on before were also reviewed. Diagnosis of the disease was based on clinical findings, positive family history of VHL, and development of a central nervous system or retinal hemangioblastoma or pheochromocytoma., Results: Based on diagnostic criteria, our initial evaluations revealed that 10 members of the family had already been affected by the disease. Among them, nine had pheochromocytoma, and one had retinal hemangioblastoma. There was no case of kidney tumors among the kindred., Conclusions: Study results show the high penetrance of the disease and focus on the large burden imposed by the disease on the health and quality of life of patients afflicted with the disease, emphasizing the importance of surveillance from early childhood for detection and management of the disease as early as possible., Competing Interests: Conflict of Interests: The authors have no conflicts of interest to declare., (Copyright © 2021, International Journal of Endocrinology and Metabolism.)

Context: Gestational diabetes mellitus (GDM) is an important endocrine disorder in perinatology, associated with several maternal and neonatal complications. Development of national guidelines can inform clinicians, health policymakers, and researchers about the most recent evidence and practical issues of diagnosis and management of GDM., Objectives: We aimed to develop clinical practice guidelines for the diagnosis and management of GDM in Iranian pregnant women., Evidence Acquisition: The Iranian Endocrine Society constituted a task force, consisting of obstetrician-gynecologists, endocrinologists, a clinical nutritionist, a clinical epidemiologist, and a librarian, to review the published literature and propose national guidelines for the diagnosis and management of GDM. The consensus was reached on all recommendations in several group meetings with a majority decision. The evidence and recommendations were graded according to the American College of Physicians' Guideline Grading System., Results: The proposed guidelines included recommendations for screening, diagnosis, and management of GDM in Iran., Conclusions: By using an evidence-based approach, these national GDM guidelines can address important clinical issues in the diagnosis and management of Iranian women with GDM., Competing Interests: Conflict of Interests: The authors declare no conflicts of interest., (Copyright © 2020, International Journal of Endocrinology and Metabolism.)

Objectives: The study aimed to compare the Modification of Diet in Renal Disease Study (MDRD) and the Epidemiology Collaboration (CKD-EPI) equations for the detection of cardiovascular risk., Methods: Data of 9,970 Tehranian participants aged ≥ 20 years were analyzed. The prevalence of cardiovascular disease (CVD), its risk factors, and 10-year atherosclerotic cardiovascular disease (ASCVD) risk were compared across the categories of glomerular filtration rate based on the MDRD and CKD-EPI equations. Chronic kidney disease (CKD) was defined as the estimated Glomerular Filtration Rate (eGFR) < 60 mL/min/1.73 m 2 according to each equation., Results: The prevalence of CKD weighted to the 2016 Tehranian urban population was 11.0% (95% confidence interval: 10.3 - 11.6) and 9.7% (9.1 - 10.2) according to the MDRD and CKD-EPI equations, respectively. Besides, 8.3% and 1.5% of the participants with CKD MDRD and non-CKD MDRD were reclassified to non-CKD CKD-EPI and CKD CKD-EPI categories, respectively. Participants with CKD CKD-EPI but without CKD MDRD were more likely to be male and older, and more frequently had diabetes, hypertension, dyslipidemia, and CVD, when compared to those without CKD according to both equations; they were also more likely to be male, older, and smokers, and had less dyslipidemia and more CVD, when compared to those with CKD by using both equations. In multivariate logistic regression analysis, compared to CKD MDRD , the odds of CKD CKD-EPI were significantly higher for older age and lower for the female gender., Conclusions: Compared to MDRD, the CKD-EPI equation provides more appropriate detection of cardiovascular risk, which is caused by the reclassification of older individuals and fewer females into lower eGFR categories., Competing Interests: Conflict of Interests: The authors declare that they have no competing interests., (Copyright © 2020, International Journal of Endocrinology and Metabolism.)

Background: The burden of chronic kidney disease (CKD) is on the rise worldwide; diabetes and hypertension are mentioned as the main contributors., Objectives: The current study aimed to investigate the multiplicative and additive interaction of diabetes and hypertension in the incidence of CKD., Methods: In this population-based cohort study, 7342 subjects aged 20 years or above (46.8% male) were divided into four groups: no diabetes and hypertension; diabetes and no hypertension; hypertension and no diabetes; and both diabetes and hypertension. The multivariable Cox regression was used to determine the effect of diabetes, hypertension, and their multiplicative interaction on CKD. The following indices were used to determine the additive interaction of diabetes and hypertension: the relative excess risk of interaction, the attributable proportion due to interaction, and the synergism index., Results: Diabetes and hypertension had no significant multiplicative interaction in men (hazard ratio of 0.93, P value: 0.764) and women (hazard ratio of 0.79, P value: 0.198); furthermore, no additive interaction was found in men (relative excess risk due to interaction of 0.79, P value: 0.199; attributable proportion due to interaction of 0.22, P value: 0.130; synergy index of 1.44, P value: 0.183) and women (relative excess risk due to interaction of -0.26, P value: 0.233, attributable proportion due to interaction of -0.21, P value: 0.266; synergy index of 0.48, P value: 0.254)., Conclusions: This study demonstrated no synergic effect between diabetes and hypertension on the incidence of CKD., Competing Interests: Conflict of Interests: The authors declare no conflict of interest., (Copyright © 2020, International Journal of Endocrinology and Metabolism.)

Competing Interests: Conflict of Interests: Authors have no financial interests related to the material in the manuscript.

Background: Thyroid cancer is the fourth most common cancer in the world. Papillary thyroid carcinoma (PTC) accounts for 80% of all types of thyroid neoplasm. Epigenetic alterations such as DNA methylation are known as the main cause of different types of cancers through inactivation of tumor suppressor genes., Objectives: In the present study, the expression and methylation of suggested gene namely nucleolar protein 4 ( NOL4 ) in PTC in comparison to multi nodular goiter (MNG) have been studied., Methods: Forty-one patients with PTC and 38 patients affected by MNG were recruited. Thyroid tissues were obtained during thyroidectomy. RNA and DNA were extracted from thyroid tissues. Quantitative RT-PCR assay was performed for determining the mRNA level of NOL4 while methylation-sensitive high resolution methylation was applied for assessing the methylation status with designing six pairs primers for six regions on gene promoter which were named from NOL4 (a) to NOL4 (f)., Results: Methylation assessment of 81 CpG islands in the promoter region of NOL4 gene revealed that NOL4 (f), the nearest region to the start codon, was significantly hypermethylated in PTC cases compared to MNG cases. NOL4 level in PTC cases in comparison with MNG cases were downregulated. The methylation status and mRNA level of NOL4 (f) were associated with age of diagnosis (Age of the patient at the time of diagnosis), lymph node metastasis, and advanced stages of disease., Conclusions: These data suggested an aberrant promoter hyper-methylation of NOL4 in PTC cases may be linked with its downregulation. Therefore, NOL4 gene can be proposed as a potential tumor suppressor gene in PTC tissues., Competing Interests: Conflict of Interests: The authors declare no competing interests., (Copyright © 2020, International Journal of Endocrinology and Metabolism.)

Context: Levothyroxine (LT4) is recommended as replacement therapy for thyroid hormone deficiency. However, some hypothyroid patients receiving LT4 therapy do not feel as well as healthy subjects. This article aimed to review current knowledge regarding LT4 monotherapy versus LT4+LT3 combination therapy and propose future directions regarding LT4+slow release T3 combination treatment for hypothyroidism., Evidence Acquisition: We searched PubMed and Scopus using related keywords., Results: The LT4 monotherapy causes higher serum free T4 (fT4), subnormal serum free T3 (fT3), and fT3/fT4 ratio in one-fourth of patients. The LT4+LT3 combination therapy increases serum T3 and fT3 concentrations and may normalize the fT3/fT4 ratio. However, the primary outcomes, including thyroid hormone deficiency, anxiety, depression, and quality of life, may not be better in LT4+LT3 combination therapy than in LT4 monotherapy. Recent surveys show that combination therapy is on the rise, in particular, due to patient demand. The LT4 plus slow-release LT3 preparation has shown promising results in improving serum thyroid hormone concentrations., Conclusions: The beneficial effect of LT4+LT3 combination therapy is not clear, and the safety of long-term therapy is yet under question. More scientific well-designed research projects are required in this field., Competing Interests: Conflict of Interests: There is no conflict of interest., (Copyright © 2020, International Journal of Endocrinology and Metabolism.)

Objectives: This study aimed to compare the effects of a three-month motivation-based educational program and conventional dietary counseling on body composition and relevant outcomes among overweight and Obese adolescents., Methods: A total of 115 overweight and obese adolescents (46% boys) were randomly assigned to either a motivation-based program or a conventional dietary counseling. The assessments were conducted at baseline and 3, 6, and 12 months after intervention., Results: Mean age and body mass index (BMI) Z-score were 14.5 ± 1.2 and 2.42 ± 0.62, respectively. Considering time trend analysis, the two groups achieved significant improvements in BMI Z-score, wrist and waist circumferences, body composition indices, and HRQoL total scores after a one-year follow-up. Wrist circumference and the HRQoL reported by parents revealed significant differences between the study groups in favor of the motivation-based program., Conclusions: Although both programs could improve anthropometric indices and HRQoL over time, the motivation-based program was more effective in reducing adolescents' wrist circumference and improving HRQoL, as the parents reported., Competing Interests: Conflict of Interests: The authors declare that they have no competing interest., (Copyright © 2020, International Journal of Endocrinology and Metabolism.)

Background: Although high blood pressure is an important risk factor for chronic kidney disease (CKD), it remains unclear whether diet can still influence the risk of CKD in adults with high blood pressure., Objectives: This study aimed at investigating the association between major dietary patterns and the incidence of CKD in adults with high blood pressure., Methods: In this cross-sectional study, we recruited 1,521 subjects aged ≥ 27 years with high blood pressure and with preserved estimated glomerular filtration rate at baseline, who participated in the fourth examination survey of the Tehran Lipid and Glucose Study. The principal component analysis was performed to derive dietary patterns. High blood pressure was defined as systolic blood pressure ≥ 120, diastolic blood pressure ≥ 80, or the current use of antihypertensive drugs. Multiple logistic regression analysis was applied to investigate the association between the dietary pattern scores and CKD risk., Results: After 3.6 years of follow-up, the incidence of CKD was 16.8%. Three dietary patterns were produced by using factor analysis, including the Western, the healthy, and the traditional Iranian dietary patterns. The healthy and the traditional Iranian dietary patterns were not related to the risk of CKD, but scoring on the Western dietary pattern was associated with enhanced odds of CKD, after being adjusted for relevant confounders (odds ratio: 2.12; 95% confidence interval: 1.19 - 3.76)., Conclusions: Results of this study provided evidence that a high score on the Western dietary pattern was associated with an increased risk of CKD in adults with high blood pressure., Competing Interests: Conflict of Interests: The authors have no conflict of interest., (Copyright © 2020, International Journal of Endocrinology and Metabolism.)

Objectives: We aimed to compare the markers of thyroid hormone status in treated euthyroid Graves' patients and levothyroxine (LT4)-treated hypothyroid Graves' patients., Methods: We collected the data of 277 patients, including 140 radioiodine-treated hypothyroid Graves' patients on LT4 treatment (group 1), 83 euthyroid Graves' patients on methimazole (MMI) therapy (group 2), and 54 euthyroid Graves' patients off MMI or radioiodine therapy for > 2 years (group 3). After the exclusion of diabetic patients, 130, 73, and 52 patients remained for analysis in groups 1, 2, and 3, respectively. Pearson and Spearman correlation coefficients were employed to assess the relationships between T3:T4 ratio and variables in each group along with univariate and multivariate linear regression models., Results: The mean age and female/male ratio were similar in the three groups. Serum fT4 was significantly higher and T3, TSH, TPOAb, and TRAb were significantly lower in group 1 than in group 2 and combined groups 2 and 3, which translated to 27% lower serum T3:T4 ratio in group 1. Higher BMI, serum cholesterol, and LDL cholesterol and lower HDL cholesterol were observed in group 1 than in combined groups 2 and 3. In multivariate regression analysis, the T3:T4 ratio was significantly higher in combined groups 2 and 3 than in group 1 in the presence of BMI and serum fasting blood glucose, triglycerides, and TSH., Conclusions: Hypothyroid Graves' patients using LT4 exhibited lower T3:T4 ratio despite lower TSH levels and their BMI and lipid parameters differed from those of euthyroid Graves' patients., Competing Interests: Conflict of Interests:The authors have no conflict of interests to declare., (Copyright © 2019, International Journal of Endocrinology and Metabolism.)

Tehran Lipid and Glucose Study (TLGS), an epidemiological study of non-communicable disease with 20 years follow up in a developing country in nutrition transition is a unique study in 15000 family based individuals, 3 - 75 years of age in a part of large city of Tehran. The success rate of recruitment for 20 years, intervention for lifestyle change, and thyroid, reproduction and cardiometabolic genetic studies derived from TLGS have paved suitable path towards precision medicine. In this review, baseline findings and changes of risk factors for the development of NCD including body weight, nutrition, physical activity, blood pressure, tobacco smoking, serum glucose and serum lipids as well as metabolic syndrome, chronic kidney disease, quality of life and biochemical findings in TLGS cohort have been summarized. The results of community based intervention for lifestyle change caused decreases in the prevalence of metabolic syndrome and the incidence of diabetes. It is concluded that TLGS has served as a model for other cohort studies in Iran and the region; it has helped to mobilize scientists in developing countries; it has established locally needed definitions of NCD variables; has served as a model for cohort studies in developing countries in nutrition transition with all socioeconomic constraints and has helped manpower education and development of local CVD risk scores for implementation of NCD management.

Context: The high prevalence of chronic diseases can be prevented or managed by specific changes in lifestyle patterns of individuals of which dietary factors is emphasized. The objective of this study was to review all findings of the Tehran Lipid and Glucose Study regarding validity and reliability of food frequency questionnaire (FFQ), evaluating dietary quality and association of dietary factors in relation to diabetes, dysglycemia, cardiovascular (CVD) and chronic kidney disease (CKD)., Evidence Acquisition: Related documents were searched through PubMed and Scopus databases, in English language from 2000 to 2017. Finally, 52 relevant documents were eligible for inclusion in this review., Results: The FFQ proved to be an acceptable tool for assessing nutrient and food group intakes and rank individuals accurately according to the levels of their dietary intakes. After 8 years of follow-up, the western dietary pattern (DP) was fairly stable but there was instability of traditional Iranian DP. DPs of over two-thirds of Tehranian populations were not in accordance with the dietary recommendations. Higher dietary scores of variety and healthy DPs were also associated with reduced odds of dysglycemia. The main dietary factor related to increased risk of CVD in our population was western DP. Patterns of amino acid intakes may contribute to the development of CVD. Higher intakes of several micronutrients and macronutrients, DPs and some vegetables decrease the risk of CKD. In conclusion DPs of most Tehranian adults need improvement., Conclusions: This review showed that higher adherence to healthy food choices was associated with reduced odds of dysglycemia and CVD. Dietary sources of renal-protective nutrients should be encouraged among the general population.

Context: Chronic kidney disease (CKD), is correlated with a substantial upsurge in mortality and morbidity worldwide. In this review, we aimed to review the 20-year-findings on CKD of the Tehran lipid and glucose study (TLGS)., Evidence Acquisition: We conducted a systematic review of all studies on CKD that had been performed in the context of TLGS., Results: Age adjusted prevalence of CKD, according to estimated glomerular filtration rate (eGFR) assessed with the two abbreviated equations of the modification of diet in renal disease (MDRD) and the CKD epidemiology collaboration (CKD-EPI) were 11.3% (95% confidence interval (CI): 10.7, 12.0) and 8.5% (95% CI: 7.9, 9.1), respectively. Using MDRD equation, over a mean follow up of 9.9 years, the incidence density rates of CKD were 285.3 person years in women and 132.6 per 10000 person-years in men. Studies on the TLGS population documented that abdominal adiposity defined as waist circumference (WC) categories (P for trend < 0.02) and waist gain in men (hazard ratio (HR) = 1.7, CI: 1.3, 2.2) significantly affected CKD development. Also, CKD had a significant effect on coronary heart disease (CHD) only in participants with low body mass index (HR = 2.06; CI: 1.28, 3.31 and HR = 2.56; CI: 1.04, 6.31 in men and women, respectively). Moreover, CKD was among the strongest independent predictors of stroke (HR = 2.01, CI: 1.22, 3.33). Also, compared to diabetic patients, an abnormal ECG was more prevalent in moderate CKD (P = 0.02)., Conclusions: Increased waist circumference and waist gain (only in men) were associated with developing CKD in the TLGS population. CKD was an independent predictor of CHD (in lean individuals) and stroke.

Context: Smoking is a global public health priority and accurate data of the local population is essential to improve the health policies against its use. Hence, this study aimed to summarize the important findings available on the prevalence of smoking and its association with non-communicable diseases, documented by one of the largest prospective community-based studies of Iran., Evidence Acquisition: All articles derived from the Tehran Lipid and Glucose Study (TLGS) in the last two decades, from the earliest publications until 30 January 2018 were reviewed for their findings on tobacco smoking., Results: The prevalence of smoking in non-diabetic adults ≥ 20 years increased between baseline (phase I, 1999 - 2001) and follow-up (phase V, 2008 - 2011) from 25.5% to 35.4% among men and from 3.4% to 6.8% among women. In TLGS adolescents (10 - 18 years) water pipe use increased between 2003 and 2005 from 35.5% to 40.9% among boys and from 19.7% to 26.1% among girls. Regarding health hazards, smoking in men was associated with increased risk of combined impaired fasting glucose/impaired glucose tolerance [hazard ratio (HR) 1.69; confidence interval (CI) 95% 1.15 - 2.48] and hypertension (HR 1.26; CI 95% 0.98 - 1.63). Moreover, men, even smoking less than 10 cigarettes per day, were at increased risk for cardiovascular diseases by HR 2.12 (CI 95% 1.14 - 3.95). For women, the risk of chronic kidney disease dramatically increased 5.74-fold (CI 95% 2.71 - 12.15) among smokers. In the whole population, smoking contributed to 7.7% of all-cause mortality with HR 1.75 (CI 95% 1.38 - 2.22). Other health aspects of tobacco smoke, including its impact on metabolic status, thyroid function, female reproductive system and life style have also been reviewed., Conclusion: Considering hazards of smoking, there is the urgency for more effective preventive measures in Iran; emphasizing the need for further local studies on the hazards of smoking with special attention to women and adolescents and the independent hazards of water pipe use.

Context: Tehran Lipid and Glucose Study (TLGS), a longitudinal family based cohort study, is the oldest and largest longitudinal family based study in Iran, aimed at investigating effects of environmental, social and biological factors on the health of Tehranians over time. Considering the importance of genetic studies in this aspect, here we present a summary of the important genetic findings, and the potentiality of their contributions to future related projects., Evidence Acquisition: For all related studies during the past 20 years the search sources were all prominent search engines such as PubMed, Scopus, and Google Scholar with the most proper Medical Subject Headings (MeSH)., Results: This review summarizes associations of 6 binary phenotypes and 17 quantitative traits with genetic markers in 26 genes. Of the 47 genetic markers, studied most were related to cardio metabolic risk factors. Results of heritability and linkage analysis were also collected and the highest heritability was found to be related to HDL-C (0.5)., Conclusion: Considering the opportunity provided by large-scale cohort studies to investigate molecular effects of genetic variants on causality and different omics' data, genetic studies conducted on TLGS population have had a remarkable success in identifying genetic variants that facilitating a unique genetic database on Iranian populations. The results of genome wide association studies in this population are currently facilitating investigations to define the Iranian genetic differences with other population.

Context: This review summarizes key findings of the Tehran thyroid study (TTS), a large scale community-based study with approximately a two decade follow-up, about the incidence, prevalence, and natural course of thyroid disorders as well as associations between thyroid diseases and metabolic syndrome (MetS), dysglycemia, and cardiovascular disease (CVD)., Evidence Acquisition: PubMed, Scopus, and Web of Science databases, and the library of Research Institute for Endocrine Sciences were used to search for TTS articles. Articles were subdivided based on the fields of prevalence, incidence and natural course, and associations of thyroid function with the incident hypertension (HTN), MetS and CVDs., Results: The 2.5th and 97.5th percentiles of serum thyrotropin (TSH) were 0.32 and 5.06 mU/L, respectively. Estimated reference intervals (2.5th and 97.5th percentiles) for thyroid peroxidase antibody (TPOAb) levels were 1.5 - 32.8 and 2.1 - 35 IU/mL in men and women, respectively. Euthyroid persistency was 93.24% during 6 years. There was a negative association between free thyroxine (FT4) levels and insulin resistance. Decreasing FT4 values over time would predict MetS in euthyroid and subclinical hypothyroid subjects (TSH < 10 mU/L). The incidence of thyroid disorders in patients with diabetes, pre-diabetes and healthy controls was 14, 18, and 21 per 1000 person-years, respectively, indicating significantly lower incidence in individuals with diabetes compared to healthy controls. Serum FT4 within the reference range was positively associated with all blood pressure (BP) measures in the total population and in men; however, serum TSH was positively associated with only systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure of men. No associations were found between various states of thyroid function and prevalence and incidence of CVD., Conclusions: A well designed cohort study aimed to investigate the gap in knowledge regarding thyroid disorders can generate many hypotheses to be examined in randomized controlled trials.

Context: The prevalence of overweight and obesity are increasing worldwide and have frequently been associated with health risks. This review highlighted several studies regarding obesity, outlining contributions of over a span of almost two decades in the Tehran Lipid and Glucose Study (TLGS)., Evidence Acquisition: A systematic review was undertaken to retrieve articles related to all aspects of obesity from the earliest available date up to January 30, 2017., Results: Prevalence of excess weight, including overweight and obesity were 20.8 and 63.6% among those aged below and above 20 years, respectively. TLGS found a high incidence of obesity with higher incidence in women among Tehranian adults; the cumulative incidence of obesity was 31.3, 38.1 and 23.4% for the whole population, women, and men, respectively. In children and adolescents, younger non-obese 7 - 9 years old, compared to 10 - 11 year olds are at greater risk of obesity. Prevalences of abdominal obesity in men and women were 52.8% and 44.4% respectively. Similar to generalized obesity, a high incidence of abdominal obesity was observed; the total cumulative incidence of abdominal obesity was 76.0% (83.6% for men and 70.9% for women). Metabolically healthy obese (MHO) and metabolically healthy abdominal obese (MHAO) are two important obesity phenotypes. People with these phenotypes have different risks for cardiovascular disease (CVD), type 2 diabetes (T2DM), and mortality. In the TLGS participants, MHO was found in 2% and 7.7% of the whole and obese population, respectively, whereas MHAO phenotype was reported in 12.4% and 23.5% of the whole and abdominal obese population. In these unstable conditions, during the long term follow up the metabolic risks developed in nearly half of the individuals. During a 12-year follow-up, incident CVD did not increase in the MHO phenotype compared to metabolically healthy normal weight (MHNW) individuals, but the risk of CVD events had increased in all metabolically unhealthy phenotypes. However in another report, over a 10-year follow-up, MHAO phenotype had an increased risk for CVD in comparison to the reference group, metabolically healthy non-abdominal obese (MHNAO) individuals., Conclusions: The TLGS studies bridged the significant gap in knowledge regarding prevalence, incidence, trends, morbidities and mortalities for obesity among Iranian population.

In the late 1990s the non-communicable diseases were becoming increasingly more prevalent and a significant proportion of evidence in this regard had originated from industrialized "Western" countries. This had led to a landscape where most national and local health decisions regarding non-communicable diseases (NCDs) were informed by data generated elsewhere. Iran, as a large country in the Middle East was no exception and was going through significant population growth and urban development at the time. An initiative by the Iranian National Scientific Research Council funded an idea that was aimed at delineating the local epidemiology of NCDs and their risk factors in a manner that was unprecedented. The result was Tehran Lipid and Glucose Study (TLGS), the first and longest running cohort of its sort in Iran. Initial data out of TLGS reported the characteristics of 15005 people aged over 3 years in a representative population of Tehranians. Additionally, distribution and prevalence of cardiovascular risk factors among the study population were characterized. This population was selected through a multistage stratified cluster random sampling technique from the population of district 13 in Tehran. In addition, TLGS gave rise to a great deal of important and highly effective initial findings on national cut-off points for various variables, information about nutrition, hypertension, dyslipoproteinemia, and metabolic syndrome. TLGS also generated information about metabolic health indicators among children and adolescents. Here we present a brief overview of rationale, design, and initial findings of TLGS.

Context: In recent decades, investigations have been focused on the definition, incidence and predictors of metabolic syndrome (MetS) in Iranians. This study aimed to review systematically investigations on MetS, conducted among the Tehran lipid and glucose study (TLGS) participants., Evidence Acquisition: Literature on MetS documented by TLGS studies published from 2000 to 2017 were searched using Pubmed and Scopus database in English language with a combination of following keywords: Metabolic syndrome, TLGS., Results: The harmonized definition of MetS was confirmed, based on the estimated cut point of waist circumference (WC) ≥ 95 cm for both genders in Iran. The incidence rate was 550.9/10000 person/years, lower among women (433.5/10000) than men (749.2/10000). The prevalence of abdominal obesity, high triglycerides (TG), low high density lipoprotein cholesterol (HDL-C), high blood pressure (BP), and high fasting blood glucose (FBG) was 30, 46, 69, 34, and 12%, respectively. The prevalence of MetS in adolescents was 10.1% with no significant difference between boys and girls (10.3% in boys and 9.9% in girls). A strong association of WC (OR: 2.32, CI: 2.06 - 2.59) and TGs (OR: 1.95, CI: 1.65 - 2.11) with development of MetS was found. In adolescent boys, WC had the highest OR for MetS risk. WHO-defined MetS was a significant predictor of total and cardiovascular mortality both in men (HR: 1.66, CI: 1.23 - 2.24; HR:1.93, CI: 1.26 - 2.94) and women (HR: 2.01, CI: 1.39 - 2.88; HR:2.71, CI: 1.44 - 5.09)., Conclusions: Our results indicate high incidence of MetS in Tehranian adults and adolescents; high WC also appears to be a strong predictor of MetS. All definitions of MetS predicted cardiovascular disease.

Context: Hypertension (HTN) is a well-known modifiable risk factor for cardiovascular disease (CVD), chronic kidney disease and mortality. Positive effects of blood pressure (BP) lowering for prevention of CVD and death have been documented in several meta-analyses of randomized controlled trials., Evidence Acquisition: This review focuses on the key findings derived from the Tehran lipid and glucose study (TLGS) papers on different aspects of BP and HTN., Results: A prevalence of 23% for HTN has been reported in the TLGS population, aged ≥ 20 years. Over a decade long follow-up, the crude incidence rate (95% CI) of new-onset HTN defined as systolic BP (SBP) ≥ 140 mmHg and/or diastolic BP (DBP) ≥ 90 mmHg, and not using antihypertensive medication was 33.63 (32.0 - 35.3) per 1000 person-years. Age, baseline SBP and body mass index were significant risk factors for development of isolated systolic HTN; regarding isolated diastolic HTN, baseline DBP and waist circumference were recognized as important risk factors whereas age, female gender and marriage were shown to be protective factors. SBP decreased significantly in both diabetic and non-diabetic participants; DBP showed a non-significant decrease in diabetic men and a statistically significant decrease in non-diabetic men. Among women, both those with and without diabetes (DM) generally experienced statistically significant decreases in DBP. Cox proportional hazard models showed that neither SBP nor DBP were associated with incident DM in the total population and in either gender, separately. All BP components were associated with CVD and all-cause mortality in the middle-aged population. Contribution of HTN to cerebrovascular events was also documented in the TLGS participants, aged ≥ 50 years., Conclusions: Several important findings regarding BP/HTN have been derived from the TLGS. According to data regarding the prevalence and incidence of preHTN and HTN and their contribution to cardiovascular morbidity and mortality in the TLGS population as a representative sample of Tehranian population, it is recommended that interventions be prioritized for lifestyle modifications for the prevention and appropriate management of preHTN/HTN.

Context: Reproductive domains of the Tehran lipid and glucose study (TLGS) are unique in that they provide reliable information on reproduction of an urban population of West Asia. The aim of this review is to present the most important reproductive findings of TLGS., Evidence Acquisition: This review is summarizing all articles published in the context of reproductive aspects of TLGS results over the 20-year follow-up. A comprehensive databases search was conducted in PubMed (including Medline), Web of Science and Scopus for retrieving articles on the reproductive histories in context of the TLGS., Results: The mean (SD) age at menarche and menopause was 13 (1.2) and 49.6 (4.5) years respectively. While pills were the most commonly used modern methods at the initiation of TLGS, the prevalence of condoms rose sharply and significantly over the follow up duration. Among women with history of gestational diabetes, the risk of diabetes and dyslipidemia progression were 2.44 and 1.2 fold higher than others. Prevalences of PCOS and idiopathic hirsutism among reproductive age participants of TLGS were 8.5% (95% CI: 6.8% - 10.2%) and 13.0% (95% CI: 10.9% - 15.1%), respectively. Trend of cardio-metabolic risk factors among women with PCOS showed that there were no statistically significant differences between mean changes of each cardio metabolic variables between PCOS and healthy women; PCOS status also significantly associated with increased hazard of diabetes and prediabetes among women aged younger than 40 years (HR: 4.9; 95% CI: 2.5 - 9.3, P value < 0.001)) and (HR: 1.7; 95% CI: 1.1 - 2.6), P value < 0.005), respectively., Conclusions: The population based nature of TLGS provides a unique opportunity for valid assessment of reproductive issues, the results of which could provide new information for modification of existing guidelines.

Context: We summarized findings from Tehran lipid and glucose study (TLGS) about different aspects of type 2 diabetes (T2D) over the span of nearly 2 decades., Evidence Acquisition: A review was undertaken to retrieve papers related to all aspects of T2D from the earliest date available up to January 30, 2018., Results: An annual crude incidence rate of 10 per 1000 person-years of follow-up was found for T2D in adult participants. Overall incidence rate of pre-diabetes/T2D was 36.3 per 1000 person-years or about 1% each year among youth. Diabetes was associated with increased risk of CVD [hazard ratio (HR): 1.86, 95% confidence interval (95% CI): 1.57 - 2.27] and mortality [HR: 2.56; 95% CI: 2.08 - 3.16] in the total population. Compared with non-diabetic men and women, their diabetic counterparts survived 1.4 and 0.7 years shorter, respectively, during 15 years of follow-up. Wrist circumference, hyperinsulinaemia, 25-hydroxy vitamin D and increase in alanin aminotranferase provided incremental prognostic information beyond the traditional risk factors for incident T2D in adults. Using decision tree algorithms, a number of high risk groups were found for incident T2D. A probability of 84% was found for incidence of T2D among a group of men with fasting plasma glucose (FPG) > 5.3 mmol/L and waist to height ratio (WHtR) > 0.56, and women with FPG > 5.2 mmol/L and WHtR > 0.56., Conclusions: Original TLGS studies have contributed greatly to clarify important evidence regarding the epidemiology and risk factors for T2D among Iranian population.

Context: Dyslipidemia, including elevated serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG), and low high density lipoprotein cholesterol (HDL-C) is a major modifiable risk factor for non-communicable diseases (NCDs). This review summarizes many of the key findings on lipid measures in the Tehran lipid and glucose study (TLGS), a large scale community-based study with an approximately two decade follow-up., Evidence Acquisition: A systematic literature search was conducted using PubMed, Scopus, Web of Science databases, and the library of the Research Institute for Endocrine Sciences, using the following keywords: Lipid measures, lipid ratios, lipid profile, dyslipidemia, and "Tehran lipid and glucose study". Articles were categorized based on fields of prevalence, trends, and impact of lipid profile on incident NCDs and mortality., Results: Between 1999 - 2001, the prevalence of high risk lipids ranged from 14% (low HDL-C) to 17% (high LDL-C) among adolescents, although among adults the lowest and highest prevalence were observed for low HDL-C (19%) and high TG (28%). Despite favorable trends for lipid parameters among adolescents, adults, and the elderly population, a considerable number of diabetic individuals, failed to achieve the optimum level of serum lipids. During follow-up, consumption of lipid-lowering drugs increased from 1.5 to 9.0% and 3.7 to 11.4% among adult men and women, respectively. The association between different lipid parameters and related ratios for incident type 2 diabetes (T2D), hypertension, metabolic syndrome and cardiovascular diseases differed between genders. Interestingly, each 1-unit increase in TC/HDL-C increased risk of hypertension among women (odds ratio (OR): 1.19, 95% confidence interval (CI): 1.00 - 1.27) and T2D among men (OR: 1.27, 95% CI: 1.06 - 1.51). Moreover, TC, LDL-C, non-HDL-C, Ln-TG, TC/HDL-C, and Ln-TG/HDL were inversely associated with non-cardiovascular mortality., Conclusions: Despite high prevalence of high risk lipid profiles among the TLGS population at baseline, favorable trends were observed in levels of all lipid components, which might be attributable to increased consumption of lipid-lowering medications and improvement in the general knowledge of Iranians regarding limited consumption of hydrogenated oil. Considering the impact of lipid profiles on incident NCDs, more attention should be paid to at-risk groups for screening and treatment purposes.

Context: The Tehran Lipid and Glucose Study (TLGS) is a community-based study to reveal the frequency of non-communicable diseases (NCDs) in Tehran's population. This research consists of two main parts, a cross-sectional study on the prevalence of cardiovascular risk factors and a 20-year-ongoing prospective cohort study, which was initiated in 1999 in several phases with an approximate duration of 3.6 years, and is still ongoing. The aim of the present study is review the 20 year biochemical findings of the TLGS related to the NCDs in a large sample., Methods: All articles on biochemical assessments derived from the TLGS from the earliest publications (2002) until 30 January 2018 were reviewed for their findings on different risk factors of NCDs., Results: According to the TLGS findings high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), homocysteine (Hcy), age, smoking, hypertension, and obesity were the most important risk factors of cardiovascular diseases (CVD). It was illustrated that in subjects with abdominal obesity, the hs-CRP and IL-6 serum levels were higher than in normal subjects. The most appropriate prognostic indexes and associations were for hs-CRP, IL-6, and Hcy with abdominal obesity, waist circumference, WHtR, and wrist circumference, respectively. Previous studies have demonstrated a direct relationship between obesity and serum levels of inflammatory factors., Conclusions: According to the results of TLGS, serum levels of biochemical risk factors such as hs-CRP, IL-6, and Hcy could be beneficial in early diagnosis and effective treatment of cardiovascular, obesity and other metabolic diseases., Competing Interests: Conflict of Interests:The authors do not report any relevant conflict of interests.

Context: Beyond the objective outcomes of metabolic syndrome (MetS), the association between this syndrome and its patient-centered outcomes need to be investigated in Middle-Eastern countries. This report aims to summarize the Tehran lipid and glucose study (TLGS) findings regarding the association between MetS and health-related quality of life (HRQoL) and its influential factors through the past decade., Evidence Acquisition: The current review has been conducted on the TLGS published data regarding different aspects of the association between MetS and HRQoL in adult participants through the last decade. To assess HRQoL, the Iranian version of short form health survey (SF-36) was used. To define MetS the most commonly used insulin resistance (IR)-and waist circumference (WC) - based MetS definitions have been applied in the publications reviewed., Results: As a whole, MetS was a determinant of poor physical HRQoL only in women (OR: 1.78; 95% CI: 1.21 - 2.61), particularly in those with more component of MetS (P < 0.001). Results further showed that only reproductive aged women with MetS were more likely to report poor PCS compared to those without MetS even after adjusting for age (OR: 1.7, 95% CI: 1.0 - 3.0; P < 0.05). Different structures of MetS and physical HRQoL constructs in men and women as well as age and smoking with significant gender-specific effects on mental HRQoL were factors responsible for the gender specific pattern observed. Considering the duration of MetS, only women with intermittent MetS indicated higher risk for reporting poor PCS (OR: 2.75, 95% CI: 1.19 - 6.37; P < 0.001) compared to those without MetS. The observed sex-specific pattern used to detect poor HRQoL in those with MetS was confirmed by all WC-based definitions except for the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) definition. However, none of IR-based definitions could detect poor physical and mental HRQoL in either gender., Conclusions: In summary, in the TLGS population, the association between MetS and HRQoL followed a sex specific pattern, mainly significant only in women and in the physical aspect.

Context: We describe here the contributions of the Tehran lipid and glucose study (TLGS) to understanding different aspects of the nitrate (NO 3 )-nitrite (NO 2 )-nitric oxide (NO) pathway in health and disease., Evidence Acquisition: All English-language documents from the TLGS, focused on NO pathway were searched using the PubMed, Scopus, and Embase databases., Results: Reference values of serum concentrations of NO metabolites (nitrate+nitrite or NOx) were 11.5 - 76.4, 10.1 - 65.6, and 10.3 - 66.8 μmol/L in men, women, and the total population, respectively. Circulating NOx was affected by age, smoking habits, menopause status, thyroid hormones, and various pathologic conditions. Elevated serum NOx was related to increased incidence of metabolic syndrome (odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.19 - 2.59), hypertriglyceridemic-waist phenotype (OR = 1.39, 95% CI = 1.05 - 1.93), chronic kidney disease (OR = 1.86, 95% CI = 1.10 - 3.14) in women, and cardiovascular disease (hazard ratio (HR) = 1.35, 95% CI = 1.01 - 1.80] in the total population. In participants with low vitamin C intake, higher intakes of NO 2 (≥ 8.77 mg/d) were accompanied with increased risk of diabetes (HR = 2.43, 95% CI = 1.45 - 4.05). A decreased risk of hypertension (OR = 0.58, 95% CI = 0.33 - 0.98) and chronic kidney disease (OR = 0.50, 95% CI = 0.24 - 0.89) was observed in response to higher intakes of NO 2 ., Conclusions: Circulating NOx is associated with and could predict the risk of metabolic disorders in a general population. Moreover, dietary NO 3 /NO 2 exposure from usual diets seems to contribute to development of noncommunicable diseases.

Context: Low physical activity is one of the major risk factors for non-communicable diseases (NCD) such as cardiovascular disease and type 2 diabetes. The current paper reviews the main findings from Tehran lipid and glucose study (TLGS) that focus on physical activity and its association with cardiometabolic risk factors over the past two decades., Evidence Acquisition: We conducted a literature search for articles from 1999 to December 2017 using the search terms: (Physical activity, leisure time physical activity, non-communicable disease, and TLGS)., Results: The prevalence of low physical activity was 69.8% during phase ΙΙ of TLGS (2000 - 2004). During 6.5 years of follow up, the prevalence of low physical activity in the total population decreased significantly between phases II (2000 - 2004) and IV of TLGS (2008 - 2010) (P < 0.05). Overweight individuals with sedentary lifestyles had a higher risk of metabolic syndrome, compared to those who had high levels of leisure-time physical activity in phase IV of TLGS (2008 - 2010); in the obese group, systolic blood pressure, and triglyceride levels differed significantly between different leisure-time physical activity categories (106.9 ± 14.3 vs. 119.1 ± 17.2 mmHg, P = 0.03) and (111.4 ± 1.6 vs. 147.1 ± 1.6 mg/dL, P = 0.01), respectively., Conclusions: The present review highlights the impact of low physical activity on the health of the TLGS community from adolescence to adulthood. The decreased prevalence of low physical activity from phase ΙΙ to phase ΙV of TLGS indicates the necessity for lifestyle interventions as a potentially effective strategy, which could have a positive impact on various risk factors and indicators of non-communicable diseases such as body mass index, waist circumference, systolic blood pressure, and lipid profiles.

Context: The Tehran lipid and glucose study (TLGS) is one of the oldest population-based longitudinal cohort studies, providing knowledge about the incidence and risk factors of some non-communicable diseases (NCDs) in West Asia which hitherto was relatively scarce. We reviewed the methods and results related to the outcome measurements of this study., Evidence Acquisition: We reviewed all the TLGS papers which reported the incidence of NCDs., Results: The TLGS was initiated in 1999 - 2001 on a population in district no. 13 of Tehran with the same age distribution of the overall Tehran population and with a middle socioeconomic status. Totally, 15005 individuals, aged ≥ 3 years, participated in the first examination; reexaminations were conducted in a triennial manner and 3550 individuals were added in the second examination. All participants were also followed up annually and asked about any medical event leading to hospitalization or death. A part of participants was assigned to an educational program for lifestyle modification. High incidence of cardiovascular disease (CVD), premature CVD, diabetes and hypertension (around 19, 6, 10 and 31 in men and 11, 5, 11 and 29 in women per 1000 person-year, respectively) besides the high incidence of pre-diabetes and pre-hypertension (around 46 and 76 in men and 37 and 49 in women per 1000 person-year, respectively) showed a worrying situation. Fortunately, the results of the community interventions were promising with around 20% reduction in the risk of metabolic syndrome up to six years., Conclusions: These precise detections of different outcomes in the TLGS provided valuable evidences for prediction and prevention of NCDs in Iran with some novelties in the middle-income countries in the world. The Tehran thyroid study (TTS) and the Tehran cardiometabolic genetic study (TCGS), conducted in the framework of the TLGS, are among few studies aiming to determine the natural course of thyroid function and to identify patterns of genetic polymorphisms related to cardiometabolic outcomes, respectively.

Context: Genetic and environmental factors contribute to the incidence of metabolic syndrome (MetS). This study aimed to review all findings of studies conducted in framework of the Tehran lipid and glucose study (TLGS) regarding the association of dietary factors with cardio-metabolic risk factors., Evidence Acquisition: All English-language studies were searched using PubMed and Scopus databases from 2000 to 2017. Finally, 105 relevant papers were included in this review., Results: Whole grains, legumes, nuts and healthy dietary patterns (DPs) reduced risk of MetS, while white rice, salty/sweet snacks increased this. The western DP had a significant interaction with APOC3, APOA1 and MC4R polymorphisms in relation to MetS. After 6.5 years of follow-up, odds of reaching menarche ≤ 12 years was significantly higher in girls with higher intakes of milk, calcium, magnesium, and phosphorous. Among children and adolescents, higher adherence to the dietary approaches to stop hypertension (DASH)-style diet decreased the risk of abdominal obesity, whereas increased adherence to the western DP could contribute to general and abdominal obesity. A three-year follow-up of adult participants showed that higher intakes of phytochemical-rich foods were inversely related to development of insulin resistance. Higher adherence to the healthy DPs was associated with the reduced risk of hyperlipidemia and hypertention. Nutrition interventions postponed rise in the prevalence of MetS. The DASH diet resulted in weight reduction compared to control diet., Conclusions: Higher adherence to healthy food choices was associated with reduced odds of MetS, abdominal obesity, dyslipidemia and hypertension. The western DP accentuated the association of polymorphisms with MetS.

Background: For addressing the burden of non-communicable diseases and policymaking, the world health organization uses World Bank income group to classify countries. This calcification method might not be optimal. This study aimed to investigate the role of World Bank income group, health expenditure, and cardiometabolic risk factors of countries in explaining the gap between their cardiometabolic mortality., Methods: In total, 190 countries were categorized into four income groups according to the World Bank definition. The energy consumption, health expenditure, and data of sex-specified age-standardized prevalence of obesity, hypercholesterolemia, hypertension, diabetes, smoking, and physical inactivity in 2008 and cardiometabolic mortality in 2012 were used. Multivariable-adjusted mixed-effect linear regression models were applied to relate country-level predictors to their mortality outcomes., Results: While the lowest cardiometabolic mortality was recorded in high-income countries in both genders, the highest rates were recorded in the low-income category for women and in low and middle-income for men. Countries had lower cardiometabolic mortality for women compared to men; however, such a difference was not shown in low-income countries. World Bank income group of countries, per se, explained one-third of the variation in their mortality outcomes while adding health expenditure, energy consumption, and cardiometabolic risk factors increased the explanatory power of the model considerably. Moreover, the more the health expenditure, the weaker the association of prevalence of hypertension with cardiometabolic mortality., Conclusions: Adding countries' health expenditure and/or the prevalence of risk factors to their World Bank income group may contribute to the better explanation of the gap between them in cardiometabolic mortality.

Background: Currently, various clinical and laboratory diagnostic methods are used to detect overt hypothyroidism during pregnancy. The Billewicz scoring index, as a clinical scale for detection of hypothyroidism, has been applied in general populations; however, its application during pregnancy remains a controversial subject of ongoing research., Objectives: The purpose of this study was to evaluate the diagnostic value of Billewicz scoring index for overt hypothyroidism in a general population of Iranian pregnant women., Methods: This study was conducted on 1843 pregnant women. A comprehensive questionnaire, including Billewicz scoring items, was completed, and relevant clinical examinations were performed. The participants underwent serum measurements of thyroxine (T4), thyroid hormone uptake, thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb). Using the receiver operating characteristic (ROC) curve analysis, the optimal sensitivity and specificity were determined as values with maximum yields on the Youden and Rsquo's Index (sensitivity + specificity-1)., Results: The prevalence of overt hypothyroidism and subclinical hypothyroidism was 3.3% and 28.6%, respectively. Overall, 3.6%, 18.9%, and 50% of euthyroid, subclinical hypothyroid, and overt hypothyroid women were TPOAb-positive, respectively. The mean Billewicz scores of euthyroid, overt hypothyroid, and subclinical hypothyroid women were -41.16 (11.16), -17.11 (13.63), and -40.1 (11.2), respectively. Based on the Billewicz scale, at least one sign of hypothyroidism was reported in 38.84% (n, 491) of euthyroid women. Scores ≤ -26.5 (sensitivity, 100%; specificity, 90.82%) were considered as the optimal scores for predicting overt hypothyroidism (Ldquo, Norisk, and Rsquo)., Conclusions: The Billewicz clinical scoring system, as a reliable and inexpensive clinical tool, used along with laboratory measurements, can help screen overt hypothyroidism during pregnancy, primarily in low-resource settings.

Background: Pre-hypertension is proposed as an independent risk factor for the incidence of cardiovascular diseases., Objectives: This study aimed to explore the main factors associated with pre-hypertension via testing a hypothesized model in Tehranian adults., Methods: The study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS) between 2009 - 2011 on 4640 adults without hypertension, aged ≥ 20 years., Results: The mean age of participants was 38.61 ± 12.14 years and 56.6% of them were female. More than one third of the studied participants had pre-hypertension (35.4%) with significantly higher prevalence in males compared to females (46.5% vs. 26.9%; χ 2 = 190.7, P < 0.001). Age, waist circumference (WC), and serum triglyceride concentrations (TG) were directly associated with pre-hypertension in both men (β = 0.16, β = 0.25, and β = 0.11, respectively) and women (β = 0.16, β = 0.21 and β = 0.09, respectively). Physical activity, only in men (β = 0.07), and marital status only, in women (β = -0.06), were also directly associated with pre-hypertension. Both healthy and poor dietary patterns showed indirect associations with pre-hypertension in both genders via WC and TG. Higher age and lower education in both genders, being married only in men, and unemployed status only in women, were positively associated with pre-hypertension via behavioral and cardio-metabolic factors., Conclusions: Level of TG and WC in both genders are direct modifiable associated factors of pre-hypertension. These findings could be considered in designing future health promotion programs aimed at preventing high blood pressure and its consequences among Tehranian adults.

Context: Insulin can be prescribed as a monotherapy or a combined therapy with other anti-diabetic medications. In this narrative review, the authors aimed to gather data related to comparison of insulin monotherapy versus combination of insulin and other anti-diabetic treatments with regards to different outcome measures in type 2 diabetes., Evidence Acquisition: This study searched and focused on the most recently published systematic reviews and their references investigating issues related to the primary aim., Results: The current data available on this topic is heterogeneous and suffers from low quality with respect to most combination treatments. Considering the efficacy and safety of combination therapy of insulin with older hypoglycemic agents, in general metformin and pioglitazone have the best and worst profiles, respectively. Compared to insulin monotherapy, combination of insulin and metformin is associated with better glycemic control, reduced daily insulin dose, less hypoglycemia, and weight gain; combination of insulin and pioglitazone results in greater hypoglycemia and weight gain and is associated with increased risk of edema and heart failure. Regarding sulphonylurea, there is some concern regarding hypoglycemia and weight gain. Addition of dipeptidyl peptidase-4 inhibitors to insulin seems to be beneficial with respect to glycemic control without any significant adverse effects. New drugs, including glucagon-like peptide-1 agonists and sodium glucose co-transporter 2 inhibitors, have acceptable profiles with significant benefits regarding weight reduction when added on insulin therapy., Conclusions: Considering the quality and longevity of evidence, compared to insulin monotherapy, insulin combined with metformin and pioglitazone has the best and worst profiles, respectively. New anti-diabetic medications have acceptable profiles yet are expensive. It is important for clinicians to meticulously weigh the advantages of combination therapy against the possible adverse effects with each drug class in every patient, individually.

Background: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The aim of this study was to investigate the association of tissue inhibitor metalloproteinase-3 (TIMP3) mRNA and protein levels in thyroid tissues, based on BRAF V600E status with the clinicopathologic characteristics of PTC., Methods: A total of 60 fresh frozen tissue samples of PTC patients (15 male and 45 female) were collected during thyroidectomy. All clinicopathological information was obtained and samples were reviewed as well as confirmed by a pathologist; exon 15 of the BRAF gene was genotyped by sequencing, TIMP3 mRNA level was assessed using SYBR-Green Real-Time PCR, and TIMP3 protein level was measured using ELISA., Results: Of 60 cases, BRAF mutation was found in 24 (40%). Larger tumor size and higher lymph node metastasis frequency were observed, significant in BRAF (+), compared to the BRAF (-) PTC group (P = 0.039 and P = 0.03, respectively). No significant difference was seen in the tumoral tissues of the TIMP3 mRNA level in BRAF (+), compared to BRAF (-) PTC samples. However, the mean TIMP3 protein level was significantly lower in tumoral tissues, compared to matched non-tumoral tissues in BRAF (+) PTC (P=0.003); TIMP3 protein level was significantly lower in tumoral tissues compared to matched non-tumoral tissues in BRAF (+), in subjects who had no lymph node metastasis and also in subjects with lymph node metastasis in both BRAF positive and negative PTC cases., Conclusion: Our results showed that BRAF mutation was associated with a larger tumor size, higher frequency of lymph node metastasis, and lower TIMP3 protein levels. Lower TIMP3 protein level was associated with the lymph node metastasis in PTC patients.

Context: Iodine deficiency is one of the most important health problems worldwide. The overall aim of this study was a narrative review of the past and present status of iodine nutrition in the Iranian population to gather and provide valuable background data in this field for future studies., Evidence Acquisition: For this narrative literature review study, published internal (SID, Iran doc, Iran medex) and international (Web of knowledge, Pubmed, SCOPUS) source studies were searched using the following medical subject heading terms: Iodine, IDD (iodine deficiency disorders), UIC (urinary iodine concentration), Goiter, IQ (intelligence quotient), thyroid hormone, Iodine and pregnancy, Iodine and breast feeding, as well as Iodized salt, reporting the prevalence of iodine deficiency and iodine nutrition status of different target populations in Iran over 25 years, between 1988 - 2014, were assessed. We found 185 abstracts by literature search, of which, 161 papers that were as case reports, animal study, with lack of regional or national data were excluded after full text evaluation. Finally 24 full papers covering regional or national data on iodine nutrition of the study population were eligible for our review., Results: Iodine deficiency, as a nutritional problem, had been identified in Iran since 1968. In the years 1987 - 1989, a few studies were done to define the prevalence of iodine deficiency in the country. The first nation-wide survey was performed in 14 provinces. Based on this survey all provinces were suffering of endemic goiter. In 1989, iodine deficiency was recognized as a major problem for community health. In 1990, salt factories began to produce iodized salt and in 1996, the second national survey was performed in 26 provinces. This survey indicated that 40% of boys and 50% of girls have goiter, with a median urinary iodine excretion of 205 µg/L. The 3rd national survey in 2001 showed that the total goiter rate is 9.8% and median UIC of 165 μg/L. In 2007, the 3th national survey was conducted 17 years after iodized salt consumption by Iranian households. In this study the total goiter rate and median urinary iodine was 5.7% and 145 μg/L, respectively. The 5th national survey conducted in 2013, showed household consumption of iodized salt for all provinces was 98% and the median urinary iodine of school children was 161 μg/L. Following the 5th national survey, the 1st national survey of the iodine status and thyroid function of pregnant women, conducted in 10 provinces in the different region of the country, documented a median UIC for pregnant women of 87.3 µg/L, results of this national survey clarified that despite iodine sufficiency of school children in Iran, pregnant women have moderate iodine deficiency and need iodine supplementation., Conclusions: The success of iodine deficiency control program depends on well designed programmatic steps and mandatory iodized salt consumption in certain situations. The iodine intake of school children is sufficient, however, Iranian pregnant women are suffering from moderate iodine deficiency and need iodine supplementation.

Background: Health-related quality of life (HRQOL) is a multi-dimensional concept that is affected by different variables. A large body of evidence shows that socio-demographic factors have a significant influence on HRQOL. When considering differences in cultural contexts and social values of various countries and the lack of evidence regarding socio-demographic determinants of HRQOL among the Iranian general population, it is important to verify the main socio-demographic determinants of HRQOL in an urban Iranian population., Objectives: This study aimed to explore socio-demographic factors associated with HRQOL and to ascertain the determinants of poor HRQOL in participants of the Tehran lipid and glucose study (TLGS)., Methods: The participants included 3491 adults, aged ≥ 20 years, who had participated in the TLGS. To obtain socio-demographic and HRQOL information, participants were interviewed by trained interviewers. Mean HRQOL scores were compared using the student's t test and analysis of variance (ANOVA). To determine significant determinants of poor HRQOL, multivariate logistic regression analysis was performed., Results: Mean ages of males and females were 47.7 ± 15.6 and 47.8 ± 14.2 years, respectively and 58.6% of participants were male. Males had significantly higher scores compared to females in both the physical and mental domains of HRQOL (P < 0.001). In males, significant determinants of poor physical HRQOL were older age, being married, being unemployed yet having other sources of income, having literacy levels below high school diploma, and having chronic diseases (P < 0.05). In females, however older age and being housewives were significant determinants of poor physical HRQOL (P < 0.05). In addition, significant determinants of poor mental HRQOL were younger age and being single or divorced/widowed in males and younger age and being illiterate as well as having literacy levels below high school diploma in females (P < 0.05)., Conclusions: Current findings highlight the importance of socio-demographic determinants of HRQOL in both genders, specifically in the physical domain, and demonstrate their roles to be more prominent in males. These findings highlight gender-specific associations between socio-demographic factors and various aspects of HRQOL among the TLGS population, which could be applied in future research focusing on non-communicable diseases and planning health promotion programs.

Background: Primordial and primary preventions of thyroid diseases are concerned with avoiding the appearance of risk factors, delaying the progression to overt disease, and minimizing the impact of illness., Summary: Using related key words, 446 articles related to primordial and primary, preventions of thyroid diseases published between 2001-2015 were evaluated, categorized and analyzed. Prevention and elimination of iodine deficiency are major steps that have been successfully achieved and maintained in many countries of the world in last 2 decades. Recent investigations related to the effect of cigarette smoking, alcohol consumption, and autoimmunity in the prevention of thyroid disorders have been reviewed., Conclusions: The cornerstone for successful prevention of thyroid disease entails timely implementation of its primordial and primary preventions, which must be highly prioritized in related health strategies by health authorities., Competing Interests: Conflict of Interest:There is no conflict of interest.

Context: Neonatal mass screening program for congenital hypothyroidism provides the best tool for prevention of its devastating effects on mental development. Despite the overall success of the screening programs in detecting congenital hypothyroidism and eliminating its sequelae and new developments made in the program design, high recall rate and false positive results impose a great challenge worldwide. Lower recall rate and false positive results may properly organize project expenses by reducing the unnecessary repeated laboratory tests, increase physicians and parents' assurance and cooperation, as well as reduce the psychological effects in families., Evidence Acquisition: In this review, we assessed the recall rate in different programs and its risk factors worldwide., Methods: Publications reporting the results of the CH screening program from 1997 to 2016 focusing on the recall rate have been searched., Results: Recall rates vary from 0.01% to 13.3% in different programs; this wide range may be due to different protocols of screening (use of T4 or TSH or both), different laboratory techniques, site of sample collection, recall cutoff, iodine status, human error, and even CH incidence as affected by social, cultural, and regional factors of the population., Conclusions: It is suggested to implement suitable interventions to reduce the contributing factors by improving the quality of laboratory tests, selecting conservative cut off points, control iodine deficiency, use of iodine free antiseptic during delivery, and use of more specific markers or molecular tests. Applying an age dependent criteria for thyrotropin levels can be helpful in regions with a varied time of discharge after delivery or for preterm babies.