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Aims: To evaluate the association between ideal cardiovascular health metrics (ICVHM) and incident low estimated glomerular filtration rate (eGFR) among the Iranian population., Methods: The study population included 6927 Iranian adults aged 20-65 years (2942 male) without prevalent low eGFR [i.e., eGFR < 60 ml/min/1.73 m2] and free of cardiovascular disease. The ICVHM was defined according to the 2010 American Heart Association. The multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratios (HRs) of ICVHM both as continuous and categorical variables., Results: Over the median of 12.1 years of follow-up, we found 1259 incident cases of low eGFR among the study population. In this population, ideal and intermediate categories of body mass index (BMI) and blood pressure (BP) and only the ideal category of fasting plasma glucose (FPG) significantly decreased the risk of developing low eGFR; the corresponding HRs and (95% confidence intervals) were (0.87, 0.77-0.99), (0.84, 0.76-0.99), (0.79, 0.68-0.93), (0.70, 0.60-0.83) and (0.76, 0.64-0.91). Also, one additional ICVHM was associated with a reduced risk of low eGFR for the global (0.92, 0.88-0.97) and biological cardiovascular health (0.88, 0.82-0.93) in these participants. A sensitivity analysis using the interval-censoring approach demonstrated that our method is robust, and results remained essentially unchanged. In a subgroup population with dietary data (n = 2285), we did not find the beneficial impact of having intermediate/ideal categories of nutrition status compared to its poor one on incident low eGFR., Conclusion: We found a strong inverse association between having higher global ICVHM with incident low eGFR among the non-elderly Iranian population; the issue is mainly attributable to normal BP, BMI, and FPG levels., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alizadeh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Determining a thyroid hormone cutoff value in pregnancy is challenging issue and several approaches have been introduced to optimize a utility function. We aimed to estimate the cutoff value of TSH using Bayesian method for prediction of preterm-birth., Methods: This study was a secondary-analysis of the population-based data collected prospectively within the framework of the Tehran Thyroid and Pregnancy Study. A total of 1,538 pregnant women attending prenatal clinics., Results: Using Bayesian method resulted a TSH-cutoff of (3.97mIU/L,95%CI:3.95-4.00) for distinguishing pregnant women at risk of preterm-birth. The cutoff was associated with acceptable positive predictive and negative predictive values (0.84,95% CI:0.80-0.88) and 0.92 (95%CI: 0.91-0.94), respectively). In women who were negative for thyroid peroxides antibody (TPOAb) with sufficient urinary iodine concentration (UIC), the TSH cutoff of 3.92 mIU/L(95%CI:3.70-4) had the highest predictive value; whereas in TPOAb positive women with insufficient UIC, the cutoff of 4.0 mIU/L(95%:CI 3.94-4) could better predict preterm birth. Cutoffs estimated in this study are close to the revised TSH value of 4.0mIU/L which is currently recommended by the American Thyroid Association., Conclusion: Regardless of TPOAb status or iodine insufficiency, risk of preterm labor is increased in pregnant women with TSH value of > 3.92 mIU/L; these women may benefit from Levothyroxine (LT4) therapy for preventing preterm birth., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rahmati et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The degree of maintaining nutrient intake patterns, conformed in the family, for offspring into adulthood is unknown. The aim of this study was to investigate the correlation between nutrient intakes in three younger-middle-older generations of Tehranian adults by sex. Of individuals who participated in 2012-15 phase of the Tehran Lipid and Glucose Study, 1286 families (4685 subjects), who had at least two members of the family with complete data in two or three generations were entered in this cross-sectional study. The energy and nutrient intakes of parents and their young or adult offspring or grandparents-grandson/granddaughter dyads were compared. The differences were estimated using pairwise t-test and partial correlation. Data of parents with their offspring were paired based on living arrangement. There were 857 fathers (mean age: 55.4±11.1) and 1394 mothers (mean age: 50.1±11.4). The mean age of grandfathers and grandmothers were 69.4±7.9 and 63.7±8.5 respectively. The significant correlation in fathers-sons and father-daughter (living with their parents) pairs were observed for 9 and 7 nutrients, respectively. Correlations for most nutrients were significant for mother-daughter or sons (living with their parents) dyads. The mean percentage of energy from total fat and trans-fatty acids of sons or daughters (living with their parents) were higher than their parents. For most nutrients, there were no significant adjusted correlations between parents-adult offspring (living independent of their parents) dyads. Also few nutrient intakes of grandparents-grandson or granddaughter dyads were correlated. The nutrient intakes of adult offspring were not associated with their parents; this correlation for younger and older generations disappeared. There were weak to moderate correlation between nutrient intakes of parent-offspring dyads that lived with their parents. The resemblance was higher for mother-offspring than father-offspring. Overall, total fat and trans-fatty acid intakes of young offspring were higher than their parents., Competing Interests: The authors have declared that no competing interests exist.

Neanderthal extinction has been a matter of debate for many years. New discoveries, better chronologies and genomic evidence have done much to clarify some of the issues. This evidence suggests that Neanderthals became extinct around 40,000-37,000 years before present (BP), after a period of coexistence with Homo sapiens of several millennia, involving biological and cultural interactions between the two groups. However, the bulk of this evidence relates to Western Eurasia, and recent work in Central Asia and Siberia has shown that there is considerable local variation. Southwestern Asia, despite having a number of significant Neanderthal remains, has not played a major part in the debate over extinction. Here we report a Neanderthal deciduous canine from the site of Bawa Yawan in the West-Central Zagros Mountains of Iran. The tooth is associated with Zagros Mousterian lithics, and its context is preliminary dated to between ~43,600 and ~41,500 years ago., Competing Interests: The authors have declared that no competing interests exist.

Considering that the data available on the cardiovascular (CV) risk of metabolically healthy obesity phenotype, and the effect of transition to an unhealthy status are inconsistent, the aim of this study was to investigate the possible role of transition to unhealthy status among metabolically healthy overweight/obese (MHO) subjects on CVD incidence over a median follow-up of 15.9 years. In this large population-based cohort, 6758 participants (41.6% men) aged ≥ 20 years, were enrolled. Participants were divided into 4 groups based on their obesity phenotypes and follow-up results, including persistent metabolically healthy normal weight (MHNW), persistent MHO, transitional MHO and metabolically unhealthy overweight/obese (MUO). Metabolic health was defined as not having metabolic syndrome based on the Joint Interim Statement (JIS) criteria. Multivariable adjusted hazard ratios (HRs) were calculated for cardiovascular events. During follow-up, rate of CVD Incidence per 1000 person-years were 12 and 7 in males and females, respectively. Multivariable adjusted HRs (CI 95%) of CVD incidence among males and females were 1.37 (.78-2.41) and .85 (.34-2.15) in persistent MHO group, 1.55 (1.02-2.37) and .93 (.41-2.12) in transitional MHO group and 2.64 (1.89-3.70) and 2.65 (1.24-5.68) in MUO group. Our findings showed that CVD risk did not increase in the persistent MHO phenotype over a 15.9-year follow-up in both sexes. However, transition from MHO to MUO status during follow-up increased the CVD risk just in male individuals. Further studies are needed to provide conclusive evidence in favor of benign nature of transitional MHO phenotype in females., Competing Interests: The authors have declared that no competing interests exist.

Context: While the role of overt hypothyroidism in lipid disorders is clear, the association between dyslipidemia and subclinical thyroid diseases remains unclarified., Objective: To examine lipid trends based on thyroid function over a 10-year period., Design: This is a prospective population based cohort study., Setting: General community., Participants: 2383 euthyroid participants, as well as those with subclinical thyroid diseases, in all residents of district 13 of Tehran were examined. Subjects who were on levothyroxine, anti-hyperthyroid drugs, and glucocorticoids, those with a history of thyroid surgery or RAI and pregnant women were excluded., Main Outcome Measures: Lipid trends in Model 1 were adjusted for age and follow up duration, and in Model 2 gender-specific multivariate adjustments were performed for thyroid status, diabetes mellitus, smoking status, education, BMI, lipid lowering medications, age and follow up duration by using generalized estimating equations., Results: In every four years of assessments, there were significant decreases in levels of all lipid parameters (all Ps <0.001) except for HDL-C, in which a decrescendo-crescendo trend was observed. The results did not change after adjusting for thyroid status, consumption of lipid lowering drugs during the follow-up period, or other variables. There were significant decreases in the prevalence of hypercholesterolemia and hypertriglyceridemia (all Ps <0.001) during the follow-up period., Conclusion: During a 10 year follow-up, decrescendo trends were observed in levels of total cholesterol, triglycerides, which were not be accounted for by the consumption of lipid lowering drugs and thyroid status., Competing Interests: There are no conflicts of interest to disclose. The authors have declared that no competing interests exist.

Objectives: To explore the association between sex-specific adiposity trajectories among Adolescents to early adulthood with incident high blood pressure (HBP) and high plasma glucose (HPG)., Methods: We studied body mass index (BMI) trajectories among1159 (male = 517) and 664 (male = 263) Iranian adolescents, aged 12-20 years, for incident HPG and HBP, respectively. Latent Class Growth Mixture Modeling (LCGMM) on longitudinal data was used to determine sex-specific and distinct BMI trajectories. Logistic regressions were applied to estimate the relationship between latent class membership with HBP and HPG, considering normal trajectory as the reference., Results: For both HBP and HPG, LCGMM determined two and three distinct BMI trajectories in males and females, respectively. During a follow-up of 12Years 104 (male = 62) and 111(male = 59) cases of HPG and HBP were found, respectively. Among females, faster BMI increases (i.e. overweight to early obese trajectory) but not overweight (i.e. those with BMI = 27.3 kg/m2 at baseline) trajectories increased the risk of HPG by adjusted odds ratios (ORs), 2.74 (1.10-5.80) and 0.79 (0.22-2.82), respectively; regarding HBP, the corresponding value for overweight to late obese trajectory was 3.72 (1.37-11.02). Among males, for HBP, the overweight trajectory increased the risk [2.09 (1.04-4.03)]; however, for incident HPG, none of the trajectories showed significant risk., Conclusions: Among females, trend of increasing BMI parallel with age can be a better predictor for risk of developing HPG and HBP than those with higher BMI at baseline., Competing Interests: The authors have declared that no competing interests exist.

Background: To investigate the associations of marital status with major clinical outcomes including type 2 diabetes (T2D), hypertension, cardiovascular disease (CVD) and all-cause mortality., Methods: The study cohort (1999-2014) included 9,737 (45% male) Iranian adults with a mean age of 47.6 years. Marital status was defined as married versus never married, divorced and widowed. The relationship between marital status and the four above mentioned outcomes were investigated using Cox regression models adjusted for the main confounders, specific to each outcome., Results: After more than 12 years of follow-up, 1,889 (883 men) individuals developed hypertension, 1,038 (468 men) T2D, 1015 (597 men) CVD and 668 (409 men) all-cause mortality. Compared with married, being never married in men was associated with higher risk of hypertension [hazard ratio (HR): 1.55; 95% confidence interval (CI), 1.11-2.16] and all-cause mortality (2.17; 0.95-5.00; p-value = 0.066) after adjusting for confounders. Among women, compared with married status, widowed status was associated with a lower risk of T2D (0.74; 0.56-0.97) in the confounders adjusted model. Moreover, never married women had a lower risk of hypertension (0.58; 0.37-0.90) compared to married ones in the age adjusted model, a finding that did not achieve significance, after further adjustment for confounders., Conclusion: We found that the relationship between marital status and health outcomes varied by gender. Being never married was an important risk factor for hypertension and tended to be a significant risk factor for mortality in men. However, among women, being widowed was associated with a lower risk of T2D., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Rodent models and studies on women with galactosemia suggest the ovo-toxicity effect of galactose. However, the association between galactose intake from dietary sources and the ovarian function in women without galactosemia has not yet been described. Therefore, this study aimed to investigate the associations between both dietary galactose and lactose intake, and ovarian dysfunction as the odds of early menopause in women without galactosemia., Materials and Methods: This cross-sectional study was conducted on 821 women without galactosemia, participants of the Tehran Lipid and Glucose Study (TLGS), who experienced natural menopause. Habitual dietary intakes of lactose and galactose during the past 12 month were assessed, using a food-frequency questionnaire (FFQ). In this study, early menopause was defined as natural menopause before the age of 45 years., Results: Mean- and menopausal age of women were reported as 59.3±7.94 and 48.6±4.81 years, respectively. No statistically significant linear association was observed between the daily intakes of lactose and galactose and the odds of early menopause. After adjusting for age, energy intake, and age at menarche, women in the middle tertiles of lactose (62%, 95%CI: 1.07, 2.46) and galactose (58%, 95% CI: 1.05, 2.39) intake had significantly higher odds of early menopause, than those in the first tertile. When the daily intake of lactose and galactose were expressed as the percentage of energy intake, the higher odds of early menopause among women in the middle tertile compared to those with the first tertile were reduced and became non-significant., Conclusion: No statistically significant linear associations were reported between the intake of lactose and galactose and age of menopause. However, the odds of early menopause in those women with the middle tertile of lactose and galactose intake were significantly higher than those women in the first tertile., Competing Interests: The authors have declared that no competing interests exist.

Purpose: This study aimed to explore the association between different obesity phenotypes and health-related quality of life (HRQoL) among Tehranian men and women., Methods: The participants of this study were 2880 healthy adults (aged>19 years) who participated in Tehran Lipid and Glucose Study (TLGS). To obtain socio-demographic and HRQoL information, participants were interviewed by trained interviewers and were stratified by body mass index categories and metabolic status. Dysmetabolic status was defined as having either metabolic syndrome or diabetes according to the Joint Interim Statement definition and American Diabetes Association. Poor HRQoL was defined as the first quartile of HRQoL scores and logistic regression analysis was used to compare sex-specific odds ratios., Results: Mean age of participants was 47.7±15.6 and 47.8±14.2 years in men and women respectively. The most and the least common obesity phenotypes were overweight-normal metabolic status and normal weight-dysmetabolic status, respectively. Only mean scores for physical HRQoL were significantly different among obesity phenotypes in both men and women (p<0.05). In addition, after adjusting for age, marital status, level of education, job status and physical activity, the odds of reporting poor physical HRQoL was significantly higher in men (OR: 1.960, 95% CI: 1.037-3.704; p<0.05) and women (OR: 2.887, 95% CI: 1.674-4.977; p<0.001) with obese-dysmetabolic status, compared to their counterparts with normal weight-normal metabolic status. However, except for overweight-normal metabolic women, who were less likely to report poor mental HRQoL (OR: 0.638, 95% CI: 0.415-0.981; p<0.05), none of the phenotypes were associated with poor mental HRQoL in either gender., Conclusions: Compared to those with normal weight normal metabolic status, only obese dysmetabolic individuals were more likely to report poor physical HRQoL in both genders., Competing Interests: The authors have declared that no competing interests exist.

Background: To examine the trend of cardiovascular diseases (CVD) risk factors among a Middle Eastern population with prevalent CVD during a median follow up of 12 years., Methods: Patients with prevalent CVD (n = 282, men = 167), with a mean age of 60.76 years were evaluated in four study phases of the TLGS (Tehran lipid glucose study), 2002-2005, 2005-2008, 2008-2011, and 2011-2014. Trends of CVD risk factors were estimated using generalized estimation equation (GEE) models, by adjusting for gender, age and propensity scores., Result: The adjusted prevalence of general and central adiposity, diabetes and physical inactivity at baseline was 25.18, 60.14, 25.03 and 43.74%, respectively and had increasing trends during the study period, reaching 41.32, 66.74, 43.20 and 50.32%, respectively, at the last visit. Although systolic, but not diastolic blood pressure, decreased from 134.88 to 129.86 mmHg, the prevalence of hypertension did not decrease (64.21% vs 68%, p value = 0.326). The prevalence of low high density lipoprotein cholesterol (HDL-C), hypertriglyceridemia and high non-HDL-C at baseline was 74.54, 59.89 and 96.53%, respectively, and showed improved trends reaching 44.87, 47.12 and 96.06% respectively; however, the favorable trend was not observed for high low density cholesterol. Significant increasing trends were observed in the consumption of anti-hypertensive, lipid and glucose lowering medications, but not for aspirin. The prevalence of current smoking (11.05 vs 16.83%, p value = 0.042) and chronic kidney disease (44.16 vs 51.65%, p value = 0.054) increased during follow up., Conclusion: Except for lipid profile status, dangerous trends for other CVD risk factors were demonstrated among CVD patients, which can be a harbinger for high rates of CVD mortality; these findings highlight the need for urgent implementation of multicomponent interventions to control CVD risk factors among these patients.

Objective: To examine associations of sex-specific related factors with pre-diabetes in Tehranian non-diabetic adults., Methods: This study has been conducted within the framework of the Tehran Lipid and Glucose Study (TLGS) between 2008-2010. A total of 5568 (55.4% female) non-diabetic adults, aged ≥20 years, selected from among participants of the TLGS, were recruited for the study. Data on socio-behavioral factors, family history of diabetes and cardio-metabolic risk factors were included in the hypothesized model to test their direct and indirect associations with pre-diabetes in men and women separately, using structural equation modeling., Results: Pre-diabetes was diagnosed in 23.6% of participants, with significantly higher prevalence in men compared to women (27.4% and 20.5%, respectively; p<0.001). Body mass index (BMI) and triglycerides (TG) in both sexes and hypertension and high density lipoprotein only in women, were directly associated with pre-diabetes (p<0.05). Poor diet in women was the only behavioral factor directly associated with pre-diabetes (p<0.05). Age in both sexes and education, only in women, were directly associated with pre-diabetes. In both genders, age, marital status, education, employment, poor diet and leisure time physical activity were indirectly associated with pre-diabetes through cardio-metabolic risk factors., Conclusions: The main modifiable factors directly associated with pre-diabetes were TG in women and BMI in men, which need to be prioritized in health policies for diabetes prevention programs in Tehranian adults. Future research should focus on the gender-specific determinants and underlying mechanisms for TG levels and BMI status among this population.

Background: Literature proves anti-mullerian hormone (AMH) and total testosterone (TT) as two important reproductive hormones in male development, however evidence regarding age variations of these hormones is lacking., Aims: To estimate the normal serum AMH values and to assess the age-specific TT levels in men aged 30-70, we conducted the present population-based study., Methods: A total of 831 healthy eligible men, aged 30-70 years, were recruited from Tehran Lipid and Glucose study cohort. Centiles for AMH were estimated according to the exponential normal 3-parameter model. The parametric method of Royston available in general software was applied for the first time to estimate the age-specific AMH and TT percentiles of 5th, 10th, 25th, 50th, 75th, 90th and 95th., Results: Mean AMH level was 6.93, ranging from 0.1 to 40.1 ng/ml. Serum AMH concentrations followed a steady reduction with increasing age. Mean TT level was 4.8, ranging from 0.44 to 11.4 ng/ml., Discussion: A measurable serum concentrations of AMH in healthy males throughout lifespan with variations, based on age, confirming a slight age-related AMH decline. Fractional polynomial (FP) regression models revealed that the mean and standard deviation (SD) of the TT were not associated with age, so the percentiles estimated were not age-specific., Conclusion: We presented a nomogram of age-specific AMH values in a healthy cohort of Iranian men. This finding might have clinical importance in dealing hormonal disorders in men.

Objective: Thyroid peroxidase antibody (TPOAb), the most common antibody frequently measured in population surveys is a protein expressed in the thyroid gland. We conducted the present study to analyze the prevalence and incidence of thyroid auto immunity and natural course of TPOAb in a population based study., Material and Methods: This prospective study was conducted within the framework of the Tehran Thyroid Study (TTS) on 5783 (2376 men and 3407 women) individuals aged ≥ 20 years who had thyroid function tests at baseline and were followed up for median 9.1 year with TPOAb measurements at approximately every 3 years., Results: The mean age of total population at baseline was 40.04±14.32. At baseline, of the 5783 participants, 742 (12.8%) were TPOAb positive, with higher prevalence among women than in men (16.0 vs. 8.5%, p = 0.001). The prevalence of TPOAb positivity in the total population was 11.9, 14.9 and 13.6% in the young, middle age and elderly respectively. The total incidence rate (95%CI) of TPOAb positivity in the total population (5020) was 7.1 (6.36-7.98) per 1000 person-years of follow-up, with higher incidence of TPOAb positivity among young participants, i.e. 8.5 (7.5-9.7) per 1000 person-years. Sex specific incidence rate demonstrated that TPOAb positivity was higher in women, 9.3 (8.2-10.7) per 1000 person-years. The Cox's proportional hazard model analysis showed that the hazard ratio of developing TPOAb positivity was higher in women than men (P<0.0001) and tended to increase slightly with serum TSH levels (P<0.0001) but declined with increasing age (P<0.0001) in the total population. Our findings demonstrate that individuals, who became TPOAb positive in each phase, had significant elevation of TSH levels at the phase of seroconversion, compared to baseline values., Conclusion: Gender, age and elevated serum TSH were found to be risk factors for developing TPOAb positivity. Furthermore, compared to baseline a significant elevation of TSH levels during seroconversion phase was observed in TPOAb positive individuals., Competing Interests: The authors declare that they have no conflict of interest.

The regularity of menstrual cycles is considered an indicator of women's reproductive health. Previous studies with a cross-sectional design have documented the relationship between menstrual cycle irregularities, insulin-resistance and the future risks for metabolic disorders. Limited data documented by prospective studies can lead to premature conclusions regarding the relationship between menstrual cycle irregularities and other conditions influencing women's health. The present study therefore, using a prospective design aimed to assess the risk of metabolic disorders in women with a history of irregular menstrual cycles, was based on the data gathered from the Tehran Lipid and Glucose study (TLGS) an ongoing prospective cohort study initiated in 1999. Participants of the current study were 2128 women, aged between 18-49 years, followed for 15 years. Based on their menstrual cycles, the women were divided into two groups: (i) women with regular menstrual cycles (n = 1749), and (ii) those with irregular menstrual cycles (n = 379). The proportional COX regression model was used to compare hazard ratios (HRs) between the groups for the proposed events, including diabetes mellitus (DM), pre-diabetes (pre-DM), hypertension (HTN), pre-hypertension (pre-HTN) and dyslipidemia. It was found that during a 15-year follow up, there were 123 cases of DM, 456 cases of pre-DM, 290 cases of HTN, 481 cases of pre-HTN, and 402 cases of dyslipidemia. Compared to those with regular cycles, women with irregular menstrual cycles were found to have an increased risk for DM2 (age adjusted Hazard Ratios (HRs), 2.01; 95% confidence intervals (CI:1.59-3.50), the increased risk for DM, associated with irregular cycles remained significant after the adjustment for Body Mass Index (BMI), fasting blood sugar (FBS), family history of diabetes, and parity (HRS, 1.73; 95% CI: 1.14-2.64). There was no significant difference in the increased risk for pre-DM between the groups (age adjusted HRs, 1.33, 95% CI: 1.05-1.69). However, after the adjustment of BMI, FBS and family history of pre-DM, compared to those with regular menstrual cycles, irregular menstrual cycles showed an increased risk for pre-DM (HRs, 1.33; 95% CI: 1.05-1.69). No statistically significant difference was found in the increasing risk for other proposed events between the groups demonstrating that menstrual cycle irregularities could be considered a marker of metabolic disorders and a predisposing factor of the increased risk for diabetes mellitus and pre-diabetes in women with irregular menstrual cycles., Competing Interests: The authors have declared that no competing interests exist.

Background: To examine the association between potentially modifiable risk factors with cardiovascular disease (CVD) and all-cause mortality and to quantify their population attributable fractions (PAFs) among a sample of Tehran residents., Methods: Overall, 8108 participants (3686 men) aged≥30 years, were investigated. To examine the association between risk factors and outcomes, multivariate sex-adjusted Cox proportional hazard regression analysis were conducted, using age as time-scale in two models including general/central adiposity: 1)adjusted for different independent variables including smoking, education, family history of CVD and sex for both outcomes and additionally adjusted for prevalent CVD for all-cause mortality 2)further adjusted for obesity mediators (hypertension, diabetes, lipid profile and chronic kidney disease). Separate models were used including either general or central adiposity., Results: During median follow-up of >10 years, 827 first CVD events and 551 deaths occurred. Both being overweight (hazard ratio (HR), 95%CI: 1.41, 1.18-1.66, PAF 13.66) and obese (1.51, 1.24-1.84, PAF 9.79) played significant roles for incident CVD in the absence of obesity mediators. Predicting CVD, in the presence of general adiposity and its mediators, significant positive associations were found for hypercholesterolemia (1.59, 1.36-1.85, PAF 16.69), low HDL-C (1.21, 1.03-1.41, PAF 12.32), diabetes (1.86, 1.57-2.27, PAF 13.87), hypertension (1.79, 1.46-2.19, PAF 21.62) and current smoking (1.61, 1.34-1.94, PAF 7.57). Central adiposity remained a significant positive predictor, even after controlling for mediators (1.17, 1.01-1.35, PAF 7.55). For all-cause mortality, general/central obesity did not have any risk even in the absence of obesity mediators. Predictors including diabetes (2.56, 2.08-3.16, PAF 24.37), hypertension (1.43, 1.11-1.84, PAF 17.13), current smoking (1.75, 1.38-2.22, PAF 7.71), and low education level (1.59, 1.01-2.51, PAF 27.08) were associated with higher risk, however, hypertriglyceridemia (0.83, 0.68-1.01) and being overweight (0.71, 0.58-0.87) were associated with lower risk., Conclusions: Modifiable risk factors account for more than 70% risk for both CVD and mortality events., Competing Interests: The authors have declared that no competing interests exist.

Introduction: To examine the associations between smoking and cardiovascular disease (CVD) / coronary heart disease (CHD) and all-cause mortality events in men with and without type 2 diabetes (T2D) in a Middle Eastern cohort during a median follow-up of 12 years., Methods: The study population included 2230 subjects aged ≥ 40 years, free from CVD, comprised of 367 participants with diabetes (21.2% current smokers) and 1863 without (27.3% current smokers). Multivariate Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for smoking (considering different definitions) for those with and without diabetes. Potential confounding factors including age, body mass index, estimated Glomerular Filtration Rate, hypertension, hypercholesterolemia and educational level were entered in the multivariate analysis., Results: In men with diabetes, the HR (95% CI) of comparing current and non-smokers was 1.25 (0.74-2.12) for incident CHD, 1.52 (0.96-2.40) for CVD and 2.10 (1.27-3.47) for mortality events; the corresponding values for men without diabetes were 1.65 (1.24-2.20), 1.70 (1.30-2.22) and 1.72 (1.14-2.58), respectively (all P values for interactions > 0.46). After pooling past smokers with current smokers, among diabetic individuals there was no significant risk for CVD [1.29 (0.89-1.86)] or mortality events [1.25 (0.81-1.92)]; however, among non-diabetic individuals the HRs of current/past smokers reached significant levels for CVD [1.53 (1.23-1.91)] but not for mortality outcomes (all P values for interactions > 0.51)., Conclusions: The strength of the associations between smoking habits and incident CVD/CHD and mortality events from all causes did not differ significantly among diabetic and non-diabetic participants. Therefore, a comprehensive community-based smoking prevention program is important, given the increasing trend of smoking among the Iranian population regardless of diabetes status.

Objective: Using structural equation modeling, this study is one of the first efforts aimed at assessing influential factors causing gender differences in the association between health-related quality of life (HRQoL) and metabolic syndrome., Methods: A sample of 950 adults, from Tehran Lipid and Glucose Study were recruited for this cross sectional study in 2005-2007. Health-related quality of life was assessed using the Iranian version of SF-36. Metabolic syndrome components (MetSCs) and physical and mental HRQoL were considered as continuous latent constructs explaining the variances of their observed components. Structural equation modeling was performed to examine the association between the constructs of MetSCs and the physical and mental HRQoL within the two gender groups., Results: Based on the primary hypothesis, MetSCs and HRQoL were fitted in a model. The negative effect of MetSCs on HRQoL was found to be significant only in the physical domain and only in women. The proportion of all the cardio-metabolic risk factors as well as subscales of physical HRQoL that have been explained via the two constructs of MetSCs and HRQoL, respectively, were significantly higher in women. Physical activity in both men (β = 3.19, p<0.05) and women (β = 3.94, p<0.05), age (β = -3.28, p<0.05), education (β = 2.63, p<0.05) only in women and smoking (β = 2.28, p<0.05) just in men, directly affected physical HRQoL. Regarding the mental domain, physical activity (β = 3.37, p<0.05) and marital status (β = 3.44, p<0.05) in women and age (β = 2.01, p<0.05) in men were direct effective factors. Age and education in women as well as smoking in men indirectly affected physical HRQoL via MetSCs., Conclusion: Gender differences in the association between MetSCs and physical HRQoL could mostly be attributed to the different structures of both MetSCs and physical HRQoL constructs in men and women. Age and smoking are the most important socio-behavioral factors which could affect this gender-specific association in the mental domain.

The aim of the study was to evaluate the association between fast food consumption and incidence of metabolic syndrome (MetS) and its components among children and adolescents over a 3.6 year follow-up. Dietary data of 424 healthy subjects, aged 6-18 years, was collected using a valid and reliable food frequency questionnaire. Metabolic syndrome was defined according to the Cook et al criteria. Consumption of fast foods including hamburgers, sausages, bologna (beef), and fried potatoes was calculated and further categorized to quartiles. Multiple logistic regression models were used to estimate the incidence of MetS and its components in each quartile of fast food intake. The incidence of MetS was 11.3% after a 3.6 year follow up. In the fully adjusted model, compared to the lowest quartile of fast food intake, individuals in the highest had odds ratios of 2.96 (95% CI: 1.02-8.63; P for trend<0.001), 2.82 (95% CI: 1.01-7.87; P for trend = 0.037), and 2.58 (95% CI: 1.01-6.61; P for trend = 0.009) for incidence of MetS, hypertriglyceridemia, and abdominal obesity, respectively. No significant association was found between fast food intakes and other components of MetS. Fast food consumption is associated with the incidence of MetS, abdominal obesity, and hypertriglyceridemia in Tehranian children and adolescents.

Objective: Prehypertension is associated with cardiovascular disease (CVD). There is no study to examine the incidence and risk factors of prehypertension in a sex stratified setting. The aim of this study was to examine the effect modification of sex for different risk factors which predicts the progression from normotension to prehypertension in a Middle East population-based cohort, during a median follow-up of 9.2 years., Methods: A multivariate Cox analysis was performed among 1466 and 2131 Iranian men and women, respectively, who were free of prehypertension, hypertension, CVD and diabetes at baseline and free of incident hypertension without preceding prehypertension at follow-up. Incident prehypertension at follow-up was defined as systolic blood pressure (SBP) of 120-139 mmHg and/or diastolic blood pressure (DBP) of 80-89 mmHg., Results: Overall, 1440 new cases of prehypertension were identified resulting in an incidence rate of 593/10000 person-years; the corresponding values for women and men were 489/10000 and 764/10000person-years, respectively. There were significant interactions between gender with age, DBP, waist-to-hip-ratio (WHpR) and estimated glomerular filtration rate (eGFR) (all P-values <0.05) in multivariate analysis. Strong associations were found between age, body mass index (BMI) and SBP with incident prehypertension in both genders. However, the effect of DBP and WHpR was significant among women and 2-hour post challenge plasma glucose (2h-PCPG)was an independent risk factor for men. In the sex-adjusted analysis, glomerular hyperfiltration [Hazard ratio (HR) and 95%CI: 1.01 (1.00-1.01), P-value = 0.02], age, BMI, WHpR, SBP and DBP had higher risks while being female [HR (95%CI): 0.81(0.69-0.94), P-value = 0.01] had a lower risk for incident prehypertension., Conclusion: According to this study results, among Iranian population with high incidence of prehypertension, general adiposity and glomerular hyperfiltration in total, 2h-PCPG in men and central adiposity in women should be emphasized as risk factors for prehypertension.

Objective: To see the changes of cardio-metabolic risk factors overtime in polycystic ovary syndrome vs. control women., Methods: This study was conducted on 637 participants (85 PCOS and 552 control reproductive aged, 18-45 years) of Tehran Lipid and Glucose Study (TLGS), an ongoing population-based cohort study with 12 years of follow-up. The cardiovascular risk factors of these groups were assessed in three-year intervals using standard questionnaires, history taking, anthropometric measures, and metabolic/endocrine evaluation. Generalized estimating equation was used to analyze the data., Results: Overall mean of insulin (3.55, CI: 0.66-6.45), HOMA-IR (0.63, CI: 0.08-1.18), and HOMA-β (45.90, CI: 0.86-90.93) were significantly higher in PCOS than in healthy women after adjustment for age, BMI, and baseline levels. However, the negative interaction (follow-up years × PCOS status) of PCOS and normal women converged overtime. Comparing third follow-up with first, insulin and HOMA-IR decreased 10.6% and 5%, respectively in PCOS women; and increased 6.7% and 14.6%, respectively in controls (P<0.05). The results did not show any significant result for other cardio-metabolic variables including WC, lipid profile, FPG, 2-h PG, SBP, and DBP., Conclusion: While the insulin level and insulin resistance rate were higher in reproductive aged PCOS than in healthy women, the difference of these risk factors decreased overtime. Thus, the metabolic consequences of PCOS women in later life may be lower than those initially anticipated.

Introduction: Polycystic ovary syndrome is a common endocrine disorder affecting women both physically and psychologically and can lead to a poor quality of life compared to their normal counterparts. The aim of the present study was to assess the impact of various clinical features of polycystic ovary syndrome on the health-related quality of life of Iranian women diagnosed with this syndrome., Materials and Methods: A total of 796 women diagnosed with polycystic ovary syndrome, aged 15-49 years, completed the questionnaires, interviews, and medical assessments required for this study. A reliable and validated Persian version of the health-related quality of life questionnaire for polycystic ovary syndrome patients was used. Linear regression models were used to assess the association between the symptoms of polycystic ovary syndrome and health-related quality of life., Results: The mean age of participants was 28.02 years. 35.4% of the subjects were classified as overweight or obese. Hirsutism, was reported to have the strongest impact on the patients' health-related quality of life, followed in descending order by body mass index, irregular menses and infertility. The relative level of hirsutism was directly proportional to decrease in health-related quality of life score (p<0.001)., Conclusions: The results of the study found that hirsutism had the strongest impact on the health-related quality of life measures in Iranian women diagnosed with polycystic ovary syndrome. Health care officials need to evaluate in depth the effect of each clinical feature of polycystic ovary syndrome separately and design management strategies, keeping in mind the psychological and physical manifestations.

Aims/hypothesis: To investigate secular trends in cardiovascular disease (CVD) risk factors during a decade of follow-up in a Middle Eastern cohort, and to compare observed trends between diabetic and non-diabetic populations., Methods: In a population of 6181 participants (2622 males and 3559 females), diabetes status and CVD risk factors were evaluated in 4 study phases from 1999-2011. 1045 subjects had type 2 diabetes mellitus at baseline and 5136 participants were diabetes-free. To examine the trends of CVD risk factors, generalized estimation equation models were constructed. The interaction between the diabetes status and each phase of the study was checked in a separate model., Results: During the follow-up period diabetic females significantly gained better control of their blood pressure, serum low density lipoprotein cholesterol and general and central obesity measures compared to non-diabetic counterparts, although 60% of them had high BP and 64% had high serum LDL-C levels till the end of the study. Diabetic males however, experienced significantly better control on their serum LDL-C and general and central obesity measures compared to their non-diabetic controls; but 24% of them were still smoker, 63% had high BP and 60% had high serum LDL-C levels at the end of the follow-up (all Ps interaction <0.05). Use of lipid-lowering and antihypertensive medications increased consistently in both diabetic and non-diabetic populations., Conclusions/interpretation: Although CVD risk factors have been controlled to some extent among diabetic population in Iran, still high numbers of people with diabetes have uncontrolled CVD risk factors that prompt more attention.

Background: Data on incidence of coronary heart disease (CHD) is scarce in the Middle East and little is known about the contribution of known risk factors in this area., Methods: The incidence of CHD and the effect of modifiable risk factors were explored in 2889 men and 3803 women aged 30-74 years in the population based cohort of the Tehran Lipid and Glucose Study, during 1999-2010. Average population attributable fraction (aPAF) was calculated for any risk factor using direct method based on regression model., Results: The crude incidence rate in men was about twice that in women (11.9 vs. 6.5 per 1000 person-years). The aPAF of hypertension, diabetes, high total cholesterol and low-HDL cholesterol was 9.4%, 6.7%, 7.3% and 6.1% in men and 17%, 16.6%, 12% and 4.6% in women respectively. This index was 7.0% for smoking in men. High risk age contributed to 42% and 22% of risk in men and women respectively., Conclusions: The incidence in this population of Iran was comparable to those in the US in the seventies. Well known modifiable risk factors explained about 40% and 50% of CHD burden in men and women respectively. Aging, as a reflection of unmeasured or unknown risk factors, bears the most burden of CHD, especially in men; indicating more age-related health care is required.

Objective: To investigate the population-based incidence of type 2 diabetes and its potential risk factors in a sex-split cohort of Iranian population., Materials and Methods: A total of 8400 non-diabetic participants, aged ≥20 years (3620 men and 4780 women) entered the study. Crude and age standardized incidence rates per 1000 person-years were calculated for whole population and each sex separately. Cox proportional hazard models were used to evaluate hazard ratios (HR) and 95% confidence intervals for all potential risk factors in both uni-variable and multivariable models., Results: During a median follow-up of 9.5 years, 736 new cases of diabetes were identified, including 433 women and 303 men. The annual crude and age-standardized incidence rates (95% CI) of diabetes in the total population were 10.6 (9.92-11.4) and 9.94 (7.39-13.6) per 1000 person-years of follow-up and the corresponding sex specific rates were 10.2 (9.13-11.4) and 9.36 (5.84-14.92) in men and 11.0 (9.99-12.0) and 10.1 (7.24-13.9) in women, respectively. In the multivariable model, the risk for incident diabetes was significantly associated with fasting and 2 hour post challenge plasma glucose as well as family history of diabetes in both men and women. However, among women, only the contribution of wrist circumference to incident diabetes achieved statistical significance [HR: 1.16 (1.03-1.31)] with waist/height ratio being marginally significant [HR: 1.02 (0.99-1.04)]; while among men, only body mass index was a significant predictor [HR: 1.12 (1.02-1.22)]. Additionally, low education level conferred a higher risk for incident diabetes only among men [HR: 1.80 (1.23-2.36); P for interaction with sex = 0.003]., Conclusion: Overall, sex did not significantly modify the impact of risk factors associated with diabetes among Iranian adults; however, among modifiable risk factors, the independent role of lower education and general adiposity in men and central adiposity in women might require different preventive strategies.

To determine, the predictors of incident metabolic syndrome (MetS) in a community-based cohort of West Asians, during a mean follow-up of 9.3 years, a sample of 2858 non-MetS Iranian adults aged ≥ 20 years were examined at baseline and followed at three year intervals during three consecutive phases. The MetS was defined using the joint interim statement. Cox proportional hazard regression was used to determine the independent variables associated with incident MetS. Overall, 1117 new cases MetS were identified resulting in an incidence rate of 550.9/10000 person years (95% CI: 519.5-584.2). The corresponding incidence rates among women and men were 433.5/10000 person years (95% CI: 398.8-471.2) and 749.2/10000 person years (95% CI: 689.9-813.5), respectively. Baseline-adjusted predictors of developing MetS included all of the MetS components, being overweight or obese in both gender, and family history of diabetes and age only in women. There were significant effect modifications of gender on age (P<0.001), high blood pressure (0.026), high waist circumference (P<0001) and obesity categories (all P ≤ 0.01) in multivariate analysis. After considering HOMA-IR in the model, among women, all of the MetS predictors as well as those with HOMA-IR ≥ 2.23 showed a significant risk for incident MetS [HR: 1.63 (1.16-2.28)]; however, among men all the MetS components (WC was marginally significant) as well as the fourth quartile of HOMA-IR [HR: 1.50 (1.03-2.17)] and being overweight showed a significant risk. Finally, in the pooled analysis, we showed that female gender had lower risk for incident MetS than male [HR: 0.58 (0.47-0.70)]. In the Iranian population, high incidence of MetS, especially among men, was shown. Our findings confirmed that sex- specific risk predictors should be considered in primary prevention for incident MetS.

The reproductive system is extremely susceptible to environmental insults, for example exogenous steroids during gestational development and differentiation. Experimental induction of androgen excess during prenatal life in female animal models reprograms their reproductive physiology, however the fetal programming of the male reproductive system by androgen excess has not been well studied. We aimed to determine the effect of prenatal exposure of two different doses of testosterone on different gestational days, on the male reproductive system using a rat model. Sixteen pregnant rats were randomly divided into two experimental groups and two control groups. Experimental group І were subcutaneously injected with 3 mg free testosterone on gestational days 16-19 and its controls received solvent for that time; experimental group П were subcutaneously injected with 20 mg free testosterone on day 20 of gestational period and its controls received solvent at the same time. The reproductive system morphology and function of 32 male offspring of these study groups were compared at days 6-30-60 of age and after puberty. The anogenital distance of the male offspring of both experimental groups had no significant differences on the different days of measurement, compared with controls. In the offspring of experimental group І, the testes weight, number of Sertoli, Spermatocyte and Spermatid cells, sperm count and motility and the serum concentration of testosterone after puberty were significantly decreased; except for reduction of sperm motility (p< 0.01), the other effects were not observed in the offspring of experimental group ІІ. In summary, our data show that prenatal exposure of male rat fetuses to excess testosterone disrupted reproductive function, an effect highly dependent on the time, duration and level of exposure. It seems that the reproductive system in individuals exposed to high levels of androgens during fetal life should be evaluated at puberty and likely to be treated.

Purpose: Studies indicate that milk intake is associated with insulin-like growth factor 1 (IGF-1) concentrations and height in childhood, whether milk and other dairy products promote puberty remains unclear. This study aimed to investigate influences of pre-pubertal intakes of milk, yogurt and cheese on menarcheal age in Tehranian girls. The associations of total dietary calcium (Ca), magnesium (Mg), and phosphorus (P) with menarcheal age were also examined., Methods: This prospective study was conducted on 134 pre-pubertal girls, aged 4-12 years at baseline, who participated in the Tehran Lipid and Glucose Study (TLGS), and were followed for a median of 6.5 years. Dietary intakes were determined at initiation of the study using two non-consecutive 24-h dietary recalls and the age of menarche was documented during the follow-up. Logistic regression was used to calculate the risk of reaching menarche ≤ 12 years according to pre-pubertal levels of dairy or mineral intakes., Results: The risk of earlier menarche was higher in girls with higher intakes of milk [OR: 2.28 (95% CI: 1.03-5.05)], Ca [OR: 3.20 (95%CI: 1.39-7.42)], Mg [OR: 2.43 (95% CI: 1.12-5.27)] and P [OR: 3.37 (95 % CI: 1.44-7.87) after controlling for energy and protein intake, interval between the age at study initiation and the age of menarche, and maternal age at menarche (Model 1). Girls in the middle tertile of cheese intakes had a lower risk of reaching menarche ≤ 12 years than those in the lowest tertile after controlling for covariates in model 1. These associations remained significant after further adjustment of BMI Z-score at baseline. The relationship of Ca, Mg, and P with menarche remained after further adjustment for height Z-score at baseline, whereas the association between milk and cheese intakes became non-significant., Conclusions: Pre-pubertal intake of milk, but not cheese and yogurt, may hasten age at menarche.

To examine, the predictors of incident chronic kidney disease (CKD) in a community-based cohort of Middle East population, during a mean follow-up of 9.9 years. In a sample of 3313 non-CKD Iranian adults ≥20 years the estimated glomerular filtration rate (eGFR) was calculated at baseline and at three year intervals during three consecutive phases. The eGFR <60 mL/min/1.73 m2 was defined as CKD. Multivariate Logistic regression analysis was used to determine the independent variables associated with incident CKD. The incidence density rates of CKD were 285.3 and 132.6 per 10,000 person-year, among women and men, respectively. Female gender per se was associated with higher risk of CKD, compared with males. Among women, age, eGFR, known diabetes, being single or divorced/widowed, hypertension (marginally significant) and current smoking were independent risk factors for CKD; however the intermediate degree of education and family history of diabetes decreased the risk by 40% (P<0.05). Among male subjects, independent predictors of developing CKD included aging and hypertension (with significantly higher risk than in women, P for interaction<0.05), eGFR, new diagnosed diabetes, high normal blood pressure; abdominal obesity decreased the risk of CKD about 30% which was marginally significant. In the Iranian population,>2% of individuals develops CKD each year. Our findings confirmed that sex- specific risk predictors should be considered in primary prevention for incident CKD.

Objective: The aim of this study was to evaluate the validity of cause of death stated in death certificates in Tehran using outcome measures of the Tehran Lipid and Glucose Study (TLGS), an ongoing prospective cohort study., Methods: The cohort was established in 1999 in a population of 15005 people, 3 years old and over, living in Tehran; 3551 individuals were added to this population three years later. As part of cohort's outcome measures, deaths occurring in the cohort are investigated by a panel of medical specialists (Cohort Outcome Panel--COP) and underlying cause of death is determined for each death. The cause of death assigned in a deceased's original death certificate was evaluated against the cause of death determined by COP and sensitivity and positive predictive values (PPV) were determined. In addition, determinants of assigning accurate underlying cause of death were determined using logistic regression model., Result: A total of 231 death certificates were evaluated. The original death certificates over reported deaths due to neoplasms and underreported death due to circulatory system and transport accidents. Neoplasms with sensitivity of 0.91 and PPV of 0.71 were the most valid category. The disease of circulatory system showed moderate degree of validity with sensitivity of 0.67 and PPV of 0.78. The result of logistic regression indicated if the death certificate is issued by a general practitioner, there is 2.3 (95% CI 1.1, 5.1) times chance of being misclassified compared with when it is issued by a specialist. If the deceased is more than 60 years, the chance of misclassification would be 2.5 times (95% CI of 1.1, 5.9) compared with when the deceased is less than 60 years.