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Background: This study was conducted to assess the prospective association between dietary polyphenols intakes and risk of metabolic syndrome (MetS) and its components., Methods: Participants in this study (n=4559) were selected from among the adults of the Tehran Lipid and Glucose Study (TLGS) with an average follow-up of 5.9+2.5 years. Biochemical and anthropometric variables were measured at baseline and follow-up examinations. A reliable and valid semi-quantitative food frequency questionnaire was used to evaluate dietary intakes. The incidence of MetS and its components in relation to polyphenols and its subclasses (phenolic acids, flavonoids, lignans, and stilbenes) was evaluated using multivariable Cox proportional hazard regression models., Results: Of the 4559 subjects who enrolled in the present study, 1765 were male aged 38.6+14.2 y and 2794 were female aged 35.9+11.7 y. The hazard ratios of MetS were 25% lower in Q2 (HR, 95% CI: 0.75, 0.64‒0.88), 22% lower in Q3 (HR, 95% CI: 0.78, 0.65‒0.94) and 24% lower in Q4 (HR, 95% CI: 0.76, 0.61‒0.95) in comparison to Q1, whereas the results for subclasses of polyphenol were non-significant. The risk of high blood pressure (BP) reduced from quartiles 1 to 4 for phenolic acid (HR: 1.00, 0.88, 0.79, 0.80, P trend =0.03). The risk of low high-density lipoprotein cholesterol (HDL-C) increased across quartiles of phenolic acid (HR: 1.00, 1.22, 1.07, 1.30, P trend =0.02)., Conclusion: This study highlights the potential protective role of total dietary polyphenols in the prevention of MetS. These findings could be the starting point of upcoming trials to illuminate the optimal level of polyphenols deriving from the intake of polyphenol-rich diets to prevent MetS., (© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Limited studies have investigated the relationship between Anti-Müllerian hormone (AMH) and metabolic syndrome (MetS), yielding inconclusive results. This study aimed to examine the relationship between AMH levels and MetS and its components in women from a general population., Methods: This prospective study recruited 769 women. Generalized Estimating Equation (GEE) models analyzed longitudinal trends of MetS components. Cox proportional hazard models evaluated effect of age-specific AMH tertiles on MetS occurrence, adjusting for confounders., Results: The GEE analysis indicated that women in the third tertile exhibited higher mean FPG compared to those in the first tertile of age-specific AMH (3 mg/dL; 95% CI: 0.40, 5.60; P = 0.024); however, this association became non-significant after adjustment. Notably, the second tertile showed a significant decrease in FPG mean changes over time (-0.69 mg/dL; 95% CI: -1.31, -0.07; P Interaction  = 0.030). Women in the second and third tertiles of age-specific AMH demonstrated lower mean HDL-C compared to the first tertile (-2.96 mg/dL; 95% CI: -4.67, -1.26; P < 0.001 and -2.63 mg/dL; 95% CI: -4.31, -0.96; P = 0.002, respectively). The association between HDL-C changes and the second tertile remained significant after adjustment (-1.91 mg/dL; 95% CI: -3.68, -0.14; P = 0.034). No significant associations were observed between age-specific AMH tertiles and TG and SBP/DBP. Cox models revealed no significant differences in the hazard ratio of MetS between AMH tertiles after adjusting for confounders., Conclusion: Despite minor variations in MetS components, AMH levels did not affect MetS risk in women from a general population., (© 2024. The Author(s).)

Background/aim: Evidence from recent studies suggested that the quality of dietary macronutrients can play a possible role in predicting the risk of metabolic disorders. In the current study, we aimed to assess the association of carbohydrate quality index (CQI) and protein score with the risk of metabolic syndrome (MetS) in Iranian adults., Methods: This prospective study was conducted within the framework of the Tehran Lipid and Glucose Study on 1738 individuals aged between 40 and 70 years old, who were followed up for a mean of 6.1 years. A food frequency questionnaire was used to determine CQI and protein scores. The multivariable adjusted Cox regression model was used to calculate the hazard ratio (HR) of MetS across quartiles of protein score and CQI, and its components., Results: The mean ± standard deviation (SD) age and body mass index of the study population (42.5% men) were 49.3 ± 7.5 years and 27.0 ± 4.0 kg/m 2 , respectively. Mean ± SD scores of CQI and protein for all participants were 12.6 ± 2.4 and 10.3 ± 3.5, respectively. During the study follow-up, 834(48.0%) new cases of MetS were ascertained. In the multivariable-adjusted model, the risk of MetS was decreased across quartiles of CQI (HR = 0.83;95%CI:0.69-1.00, P trend =0.025) and protein score (HR = 0.75; 95% CI:0.60-0.94, P trend =0.041). Also, Of CQI components, the whole grain/total grains ratio showed a significant inverse association with the risk of MetS (HR = 0.75;95%CI:0.60-0.94, P trend =0.012)., Conclusion: Our findings revealed that a dietary pattern with higher CQI and protein score may be related to a reduced risk of MetS in adults., (© 2024. The Author(s).)

Aims/introduction: The aim was to examine the joint effect of metabolic syndrome (MetS) and insulin resistance (IR) with ideal cardiovascular health (iCVH) status on incident cardiovascular diseases (CVDs)., Materials and Methods: The study included 6,240 Iranian adults ≥30 years, free of prior cardiovascular disease. Ideal cardiovascular health was determined based on American Heart Association's Life Simple 7. Metabolic syndrome was defined according to the Joint Interim Statement Criteria, and insulin resistance was defined as HOMA-IR ≥1.85 in women and ≥2.17 in men. Multivariable Cox proportional hazard ratios (HRs) were applied to examine the impact of metabolic syndrome, and insulin resistance at various levels of iCVH status., Results: During the median follow-up of 14.0 years, 909 cases of cardiovascular disease occurred. Metabolic syndrome and insulin resistance were significantly associated with incident cardiovascular disease events. In the poor and intermediate status, metabolic syndrome increased cardiovascular disease events with HRs of 1.83 and 1.57, respectively; the corresponding values for insulin resistance in the mentioned categories were 1.91 and 1.25, respectively (P values < 0.05). In the intermediate and poor iCVH status, hypertriglyceridemia was linked to a 40% and 35% higher risk of cardiovascular disease, the corresponding values for low HDL-C was 20% and 60%, respectively (P values < 0.05). Although adding metabolic syndrome, its dyslipidemia and insulin resistance to iCVH status in both poor and intermediate status significantly improve the prediction of cardiovascular disease using net reclassification improvement (P values < 0.05), the value of C-index did not change., Conclusions: Metabolic syndrome and the dyslipidemia component had a negligible but significant improvement in the prediction of cardiovascular disease among individuals with non-optimal iCVH status., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Purpose: Hyperandrogenic intrauterine environment may lead to the development of metabolic disorders in offspring in their later life. In this study, we aimed to determine the impact of maternal hyperandrogenism (MHA) on metabolic syndrome (MetS) risk in female offspring in their later life., Methods: In this cohort study conducted in Tehran, Iran, female offspring with MHA (n = 323) and without MHA (controls) (n = 1125) were selected. Both groups of female offspring were followed from the baseline to the date of the incidence of events, censoring, or end of the study period, whichever came first. We used age-scaled unadjusted and adjusted Cox regression models to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MHA and MetS in female offspring. The software package STATA was used for statistical analysis, and the significance level was set at P < 0.05., Results: We observed a higher risk of MetS (unadjusted HR (95% CI), 1.36 (1.05-1.77)), (P = 0.02) and (adjusted HR (95% CI), 1.34 (1.00-1.80)), (P = 0.05, borderline)), in female offspring with MHA, compared to controls. The results were adjusted for the potential confounders including body mass index (BMI) at baseline, net changes of BMI, physical activity, education status, and birth weight., Conclusion: Our results suggest that MHA increases the risk of developing MetS in female offspring in their later life. Screening of these female offspring for MetS may be recommended., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The available evidence indicates that the severity of metabolic syndrome tends to worsen progressively over time. We assessed the trajectory of age and sex-specific continuous MetS severity score (cMetS-S) and its association with the development of diabetes during an 18-year follow-up., Methods: In a prospective population-based Tehran Lipid and Glucose Study, 3931 eligible participants free of diabetes, aged 20-60 years, were followed at three-year intervals. We examined the trajectories of cMetS-S over nine years using latent growth mixture modeling (LGMM) and subsequent risks of incident diabetes eight years later. The prospective association of identified trajectories with diabetes was examined using the Cox proportional hazard model adjusting for age, sex, education, and family history of diabetes, physical activity, obesity (BMI ≥ 30 kg/m 2 ), antihypertensive and lipid-lowering medication, and baseline fasting plasma glucose in a stepwise manner., Results: Among 3931 participants, three cMetS-S trajectory groups of low (24.1%), medium (46.8%), and high (29.1%) were identified during the exposure period. Participants in the medium and high cMetS-S trajectory classes had HRs of 2.44 (95% CI: 1.56-3.81) and 6.81 (95% CI: 4.07-10.01) for future diabetes in fully adjusted models, respectively. Normoglycemic individuals within the high cMetS-S class had an over seven-fold increased risk of diabetes (HR: 7.12; 95% CI: 6.05-12.52)., Conclusion: Although most adults exhibit an unhealthy metabolic score, its severity usually remains stable throughout adulthood over ten years of follow-up. The severity score of metabolic syndrome has the potential to be utilized as a comprehensive and easily measurable indicator of cardiometabolic dysfunction. It can be employed in clinical settings to detect and track individuals at a heightened risk of developing T2DM, even if their glucose levels are normal., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The association between individual dietary fatty acids (FAs) and risk of metabolic syndrome (MetS) has been investigated in previous studies. However, synergistic or additive effects of multiple FA have received less attention. Hence, we aimed to determine the major dietary FA patterns and evaluate the association between FA patterns and risk of MetS., Methods: Dietary intakes of 1713 MetS-free adults who participated in the third phase of the Tehran Lipid and Glucose Study (TLGS) were assessed using a validated 168-items food frequency questionnaire. FA patterns were obtained by principal component analysis (PCA). Adjusted Hazard Ratios (HRs) and 95% confidence intervals (CIs) were calculated for the association of MetS incident with the extracted FA patterns., Results: Four major FA patterns were identified through PCA of the 24 FAs consumed: "short- and medium-chain saturated fatty acid (SFA) pattern", "long-chain FA pattern", "omega-3 PUFA pattern", and "long-chain SFA pattern". There was no significant association between dietary FA patterns and risk of MetS incidence., Conclusions: We found no significant association between FA patterns and risk of MetS. More prospective cohort studies and clinical trials are needed to clarify the issue., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Traditional metabolic syndrome (MetS) criteria have several limitations, which hinder its use in clinical practice. To overcome the limitations, we investigated the association between age- and sex-specific continuous MetS severity score (cMetS-S) and cardiovascular disease (CVD) and mortality beyond MetS components in the framework of the Tehran Lipid and Glucose Study. Participants aged 20-60 years at baseline were included in the study. We excluded participants with CVD, cancer, use of corticosteroids, estimated glomerular filtration rate < 30 ml/min/1.73 m 2 , and those who were pregnant. We evaluated the association between cMetS-S with CVD and mortality over 18 years of follow-up among 8500 participants with continuous and quantile approaches using the Cox proportional hazard regression model. In addition, the model performance of cMetS-S for predicting CVD events was compared to the conventional MetS criteria. Participants with higher cMetS-S had a significantly increased risk for CVD, coronary (CHD) and non-coronary heart disease (non-CHD), and all-cause, cardiovascular, and sudden cardiac death. Independent of the confounders and MetS components, the cMetS-S had the HRs of 1.67 (95% CI 1.47-1.89), 1.60 (95% CI 1.37-1.86), and 1.88 (95% CI 1.50, 2.35) for CVD, CHD, and non-CHD events upon 1-SD increment, respectively. The risk of mortality was increased for 1-SD of cMetS-S (all-cause mortality, HR 1.24; 95% CI 1.09-1.41; CVD mortality, HR 1.72; 95% CI 1.20-2.45; sudden cardiac death, HR 1.60; 95% CI 1.03-2.49). The model fitness of cMetS-S was superior to the conventional MetS criteria in predicting CVD and mortality. The cMetS-S provided an additional risk for CVD and mortality beyond the individual MetS components. Standardized cMetS-S could be a potential universal measure to define MetS severity while considering the weighted contribution of MetS components and their variations by age, sex, and ethnicity., (© 2023. Springer Nature Limited.)

Objective: We aimed to investigate the associations of macronutrient quality indices with the incident metabolically unhealthy normal weight (MUNW) and metabolically unhealthy overweight/obesity (MUO) phenotypes., Methods: This prospective study included 512 metabolically healthy normal weight and 787 metabolically healthy overweight/obese adults from the third study examination of the Tehran Lipid and Glucose Study. The participants were followed through the sixth study examination. Diet was measured with a food frequency questionnaire. The macronutrient quality index (MQI), carbohydrate quality index (CQI), fat quality index (FQI), and healthy plate quality index (HPPQI) were calculated. Hazard ratio (HR) and 95 % confidence interval (95 % CI) were estimated for incident unhealthy phenotypes using Cox regression., Results: After controlling all possible confounding factors, a one-point higher HPPQI was linked to a 28 % lower risk of MUNW (HR = 0.72; 95 % CI = 0.59, 0.87). Compared to the lowest quartile, the incident MUNW was also lower in the two last quartiles of the HPPQI. A one-unit increase in MQI was associated with a 5 % lower incident MUO (HR = 0.95; 95 % CI = 0.92, 0.99). The incident MUO was also higher for the highest compared to the lowest MQI quartile. In quartiles 2-4 of the HPPQI, incident MUO was lower with respective HRs (95 % CI) of 0.71 (0.54, 0.93), 0.60 (0.45, 0.80), and 0.66 (0.50, 0.86) in the fully-adjusted model., Conclusions: A higher overall macronutrient quality was independently associated with a lower incident MUO. A higher dietary protein quality was related to a lower risk for MUNW and MUO., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to examine the gender differences in the association between status changes of metabolic syndrome (MetS) and its components, using Joint Interim Statement (JIS) criteria, with the risk of type 2 diabetes mellitus (T2DM) among an urban population., Methods: The study included 4,463 Iranian adult participants (2,549 women) aged ≥20 years. Based on status changes of MetS and its components during 3 years, subjects were categorized into four groups: MetS-free (reference), MetS-developed, MetS-recovery, and MetS-stable. A similar categorization was applied to MetS components. Multivariable Cox regression models were used for estimating hazard ratios (HRs) and women-to-men ratios of HRs (RHRs)., Results: During a median follow-up of 9.3 years, 625 T2DM events (351 women) occurred. Compared with the reference, the HRs of the MetS-developed, -recovery, and -stable groups among men for incident T2DM were 2.90, 2.60, and 4.92; the corresponding values for women were 2.73, 2.88, and 5.21, respectively (all p -values < 0.01), without significant gender difference in these relationships. In both genders, the fasting plasma glucose (FPG) component, regardless of the change in status, was strongly and significantly associated with incident T2DM with HRs ranging from 2.49 to 9.42; a similar association was also found for high waist circumference (WC)-recovery and -stable groups, with HRs ranging from 1.58 to 2.85 ( p -values ≤ 0.05). Regarding gender differences, the development and persistence of high blood pressure (BP) status exposed men to greater T2DM risk than women with women-to-men RHRs of 0.43 (0.26-0.72) and 0.58 (0.39-0.86), respectively. Moreover, stable low levels of high-density lipoprotein cholesterol (HDL-C) and high triglyceride (TG) levels conferred higher T2DM risk in women than in men, with women-to-men RHRs of 1.67 (0.98-2.86) and 1.44 (0.98-2.14), respectively (both p -values = 0.06)., Conclusion: Among Tehranian adults, in both genders, all status changes of MetS, even those recovered from MetS, have a higher risk of T2DM compared to those who never had MetS. Also, all statuses of high FPG, in addition to recovered and stable high WC, were strongly associated with T2DM risk. Specifically, men with stable or developed high BP and women with stable dyslipidemic status were at differentially increased risk of incident T2DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hadaegh, Abdi, Kohansal, Hadaegh, Azizi and Tohidi.)

Metabolic syndrome (MetS), defined as the coexistence of interrelated cardiometabolic risk factors, is limited by ignoring the severity of the disease and individuals with a pre-metabolic state. We aimed to develop the first age- and sex-specific continuous MetS severity score in the adult population using confirmatory factor analysis (CFA) based on the MetS components in the Middle East. Using data from the population-based Tehran Lipid and Glucose Study (TLGS) I and II datasets, we conducted CFA of the single factor MetS on 8933 adults (20-60 years old) totally, and in age and sex subgroups. We allowed for different factor loadings across the subgroups to formulate age- and sex-specific continuous MetS severity score equations. Thereafter, we validated these equations in the dataset of TLGS III participants. Triglyceride had the highest factor loading across age and sex subgroups, indicating the most correlation with MetS. Except for women aged 40-60 years, waist circumference was the second most significant factor contributing to MetS. Systolic blood pressure was more closely related to MetS in women than in men. Systolic blood pressure and fasting plasma glucose had the weakest correlation with MetS among the 40-60 age group. Moreover, as women age, the contribution of fasting plasma glucose to MetS tended to decline, while it remained relatively constant in men. The resulting MetS severity score was correlated with age and homeostasis model assessment of insulin resistance. Furthermore, the continuous MetS severity score well predicted the traditional MetS according to receiver operating characteristic analysis in the validation dataset. The age- and sex-specific continuous MetS severity score for the West Asian adult population provides a tangible quantitative measure of MetS enabling clinicians to screen and monitor the individuals at risk and assess their metabolic trends., (© 2023. The Author(s).)

Background: A metabolically unhealthy phenotype is associated with the risk of cardiometabolic events and can be prevented by adherence to healthy dietary patterns. The present study was designed to investigate the association between high adherence to the Dietary Approaches to Stop Hypertension (DASH), Mediterranean (MeDi), and Mediterranean-DASH intervention for neurodegenerative delay (MIND) diet scores and the incidence of metabolically unhealthy phenotypes in adults across body mass index (BMI) categories., Methods: In this cohort study, 512 subjects with metabolically healthy normal weight (MHNW) at baseline and 787 subjects with metabolically healthy overweight/obesity (MHOW/MHO) at baseline were included. Dietary intake was collected by a validated food frequency questionnaire, and DASH, MeDi, and MIND scores were calculated. The Joint Interim Statement (JIS) criteria were used to define a metabolically unhealthy status., Results: A total of 137 and 388 subjects with metabolically unhealthy normal weight (MUNW) and metabolically unhealthy overweight/obesity (MUOW/MUO) phenotypes, respectively, were observed, over a mean of 5.91 years of follow-up. The Cox proportional hazard regression indicated participants in the third tertile of the DASH score had a lower risk of the MUNW phenotype (HR: 0.59; 95% CI: 0.37-0.92) than those in the lowest tertile. Similarly, the highest adherence to the MeDi and MIND scores was also linked to a 46% (HR: 0.54; 95% CI: 0.36-0.81) and 47% (HR: 0.53; 95% CI: 0.34-0.83) lower risk of the MUNW phenotype, respectively. As well, there was an inverse relationship between the highest adherence to the DASH (HR: 0.66; 95% CI: 0.50-0.86), MeDi (HR: 0.74; 95% CI: 0.58-0.93), and MIND (HR: 0.57; 95% CI: 0.43-0.74) scores and the risk of MUOW/MUO. There was no interaction between age and the three dietary patterns in relation to a metabolically unhealthy phenotype., Conclusion: High compliance with the DASH, MeDi, and MIND scores was associated with a lower risk of MUNW. An inverse relationship between these three dietary patterns and the incidence of the metabolically unhealthy phenotype was also observed in individuals who had MHOW/MHO at baseline., Competing Interests: Conflict of Interest The authors declare no competing interests., (Copyright © 2023 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

The current study aimed to examine the possible association of the dietary index for insulin resistance (DIR) and the lifestyle index for insulin resistance (LIR), determined by dietary components, body mass index, and physical activity, with the risk of cardiometabolic diseases, including insulin resistance (IR), hypertension (HTN), diabetes, and metabolic syndrome (MetS). This prospective cohort study was performed on 2717 individuals aged ≥ 19 years in the framework of the Tehran Lipid-Glucose Study. Data on nutritional intakes were assessed using a validated food frequency questionnaire. Logistic regression models were used to determine the odds ratio and 95% confidence intervals (ORs and 95% CIs) of cardiometabolic diseases across tertiles of DIR and LIR scores. During 3-years of follow-up, the incidence rate of diabetes, IR, HTN, and MetS was 3%, 13%, 13.9%, and 17%, respectively. In the multi-variables model, after controlling all potential confounders, the risk of IR(OR: 1.65, 95% CI 1.01-2.69, P-trend = 0.047), diabetes (OR: 1.95, 95% CI 1.02-3.74, P-trend = 0.058), and HTN(OR: 1.52, 95% CI 1.07-2.15, P-trend = 0.016) was increased across tertiles of DIR score. Also, the risk of IR (OR: 2.85, 95% CI 1.72-4.73, P-trend < 0.001), diabetes(OR: 2.44, 95% CI 1.24-4.78, P-trend = 0.004), HTN(OR: 1.95, 95% CI 1.35-2.81, P-trend < 0.001), and MetS (OR: 2.87, 95% CI 1.96-4.18, P-trend < 0.001) were increased across tertiles of LIR score. Our findings reported that a dietary pattern with a higher DIR score and a lifestyle with a higher LIR score might be related to increased cardiometabolic disorders, including diabetes, HTN, Mets, and IR in Iranian adults., (© 2023. The Author(s).)

Background: Chronic kidney disease (CKD) can progress over time and cause renal replacement therapy. Studies showed the association between metabolic syndrome (MetS) and CKD. Current evidence is from cross-sectional studies. There is a need for the robust data from big prospective cohort studies with long-term follow-up. This study investigated the association between CKD and MetS after 18 years of follow-up., Material and Method: Among 15,255 participants aged ≥20 years at baseline (1999-2005), after exclusion of CKD, cancer, and use of corticosteroids, 8987 participants entered the study and followed at a three-year cycle up to 2018. All participants were divided into five subgroups: (1) MetS-free, (2) MetS (DM+, HTN-), (3) MetS+ (DM-, HTN+), (4) MetS+ (DM+, HTN+) and (5) MetS+ (DM-, HTN-)., Result: At baseline, the mean age of the participants was 39.8 ± 13.3 years; 4996 (55.6%) were females. CKD was developed in 2038 (22.7%) subjects during 18 years of follow-up, of whom 1107 had MetS. After adjusting for the confounding variables, MetS (DM+, HTN+) subgroup had the highest risk of CKD (HR = 1.51, 95% CI = 1.32-1.71). MetS subjects with five components had a higher incidence rate of CKD (HR = 1.43, 95% CI = 1.22-1.68). There was no association between high waist circumference (WC) (HR = 1.08, 95% CI = 0.99-1.19) and high-density lipoprotein (HDL) (HR = 1.07, 95% CI = 0.98-1.18) with CKD., Conclusion: CKD significantly develops in patients with MetS. Metabolic syndrome was associated with the development of chronic kidney disease incidence. Hypertension, diabetes, and age were strong indicators, while abdominal obesity and reduced HDL were not associated with the incidence of CKD., (© 2023 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Despite the many signs of progress in pharmacotherapies, metabolic syndrome (MetS) is one of the main public-health burdens worldwide. Our study aimed to compare the effect of breastfeeding (BF) in women with and without gestational diabetes mellitus (GDM) on MetS incidence., Methods: Of females who participated in the Tehran Lipid and glucose study, women who met our inclusion criteria were selected. The Cox proportional hazards regression model, with adjustment of potential confounders, was done to evaluate the relationship between duration of BF and incident of MetS in women with a GDM history compared to non-GDM., Results: Out of 1176 women, there were 1001 non-GDM and 175 GDM. The median follow-up was 16.3 (11.9, 19.3) years. Results of the adjusted model illustrated that the total BF duration was negatively associated with MetS incidence risk (hazard ratio (HR) 0.98, 95% CI 0.98-0.99) in total participants indicating that per one-month increase of BF duration, the hazard of MetS reduced by 2%. The HR of MetS in Comparison between GDM and non-GDM women demonstrated significantly more reduced MetS incidence with a longer duration of exclusive BF (HR 0.93, 95% CI 0.88-0.98)., Conclusions: Our findings illustrated the protective effect of BF, especially exclusive BF, on MetS incidence risk. BF is more effective in reducing the risk of MetS among women with a history of GDM than among women without such a history., (© 2023. The Author(s).)

Introduction: The current study aimed to investigate the association of three stable obesity phenotypes (persistent metabolically healthy normal weight [P MHNW], persistent metabolically healthy obese [P MHO], persistent metabolically unhealthy obese [P MUO]), and one transient (MHO to MUO) obesity phenotype throughout 18 years with health-related quality of life (HRQoL)., Methods: 1,932 participants (649 men and 1,283 women) who completed the HRQoL questionnaire during 2016-2019 were recruited in the current investigation. Based on the body mass index and metabolic status, participants were classified into four obesity phenotypes, including (1) P MHNW, (2) P MHO, (3) P MUO, and (4) transient from MHO to MUO. The HRQoL was compared between groups using analysis of covariance. Participants' age, marital status, occupation status, education level, physical activity, and smoking were adjusted., Results: After adjustment for confounder variables, a significant difference among obesity phenotypes was indicated in (physical component summary) PCS scores of both sexes and (mental component summary) MCS scores just in women (p value = <0.001). The P MUO had the lowest scores in PCS and MCS, and P MHO had the highest MCS scores compared to other obesity phenotypes in either sex., Conclusion: The results of the present study indicate the negative effect of long-term concurrence of obesity and metabolic disorders on the HRQoL of adults. However, long-term obesity alone or loss of metabolic health in the short term did not affect individuals' assessment of their physical and mental health. These findings highlight the importance of preventive interventions in people with obesity; also indicate the need for awareness-raising strategies about healthy lifestyles to improve the quality of life in society., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

This study investigated the association between ultra-processed foods (UPF) and the risk of metabolically unhealthy normal weight (MUNW) and metabolically unhealthy overweight/obese (MUO). We included 512 normal-weight and 787 overweight/obese adults with a metabolically healthy phenotype from the Tehran and Lipid Glucose Study, who were followed from the third (baseline) to the sixth study examinations. Each 10% increase in energy intake from UPF was related to a 54% (95% CI = 21-96%) and 2% (95% CI = 1-3%) higher risk of MUNW and MUO, respectively. The risk of MUNW was significantly higher in quartile 4 compared to quartile 1. The restricted cubic splines suggested that the risk of MUNW increases monotonically when UPF accounts for at least 20% of energy intake. No non-linear association was observed between UPF and the risk of MUO. Energy intake from UPF was positively related to the risk of MUNW and MUO.

Background: A limited number of studies have investigated the impact of idiopathic hirsutism (IH) on cardiometabolic parameters with contradictory and inconclusive results. This study aimed to explore the effect of IH on metabolic outcomes., Method: In this population-based prospective study, 334 women with IH and 1226 women as healthy controls were selected from Tehran Lipid and Glucose Study. The generalized estimation equations method was applied to investigate the secular longitudinal trends of metabolic indices, including fasting blood sugar (FBS), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL), non-HDL, triglyceride (TG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and waist circumference (WC) in both groups. Unadjusted and adjusted Cox regression models were applied to assess the hazard ratios (HR) and 95% CIs for the association between IH and metabolic disorders. Potential confounding factors such as age, body mass index, smoking, physical activity, history of hypertension (HTN), and family history of diabetes were included in the adjusted model., Results: This study showed that compared with healthy controls, women with IH had lower SHBG and higher total testosterone (median [interquartile ratio; IQR]: 0.37 [0.16-0.70] vs 0.33 [0.14-0.58]; P = 0.01), free androgen index (median [IQR]: 0.85 [0.38-1.54] vs 0.54 [0.26-0.97]; P = 0.001), androstenedione (median [IQR]: 1.60 [1.00-2.25] vs 1.10 [0.90-1.70]; P = 0.001), and dehydroepiandrosterone sulfate (median [IQR]: 168.5 [91.1-227.8] vs 125.2 [66.3-181]; P = 0.001). Over time, mean changes of FBS, HDL-C, LDL-C, non-HDL-C, TG, SBP, DBP, and WC were not significantly different in women with IH, compared with healthy controls. According to the unadjusted Cox regression model, except for type 2 diabetes mellitus (T2DM) (HR [95% CI]: 1.45 [1.00-2.11]) P = 0.05; there was no statistically significant difference in hazard of metabolic disorders (ie, HTN, pre-HTN, pre-T2DM, and metabolic syndrome) in IH, compared with healthy controls. Besides, the adjusted Cox regression model showed no significant differences in the hazard of these outcomes., Conclusion: This study showed no significant difference in overtime mean changes of metabolic risk factors and cardiometabolic outcomes in women with IH, compared with the healthy control group, except marginally significant difference on T2DM, which disappeared after further adjustment for potential confounders. Accordingly, routine screening of women for these metabolic outcomes should not recommend., Competing Interests: Conflicts of Interest The authors have no conflict of interest to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: To evaluate the impact of different definitions of metabolic syndrome (MetS) and their components on the risk of sudden cardiac death (SCD) among the Iranian population according to the World Health Organization (WHO), International Diabetes Federation (IDF), Adult Treatment Panel III (ATP III), and Joint Interim Statement (JIS) criteria., Methods: The study population included a total of 5,079 participants (2,785 women) aged ≥ 40 years, free of cardiovascular disease (CVD) at baseline. Participants were followed for incident SCD annually up to 20 March 2018. Multivariable Cox proportional hazards regression models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of MetS and its components for incident SCD., Results: The prevalence of MetS ranged from 27.16% to 50.81%, depending on the criteria used. Over a median of 17.9 years of follow-up, 182 SCD events occurred. The WHO, IDF, and JIS definitions were strong predictors of SCD with multivariable-adjusted HRs (95% CI) of 1.68 (1.20-2.35), 1.51 (1.12-2.03), and 1.47 (1.08-1.98), respectively; these associations significantly attenuated after further adjustment for MetS components. MetS by the ATP III definition was not associated with the risk of SCD after controlling for antihypertensive, glucose-lowering, and lipid-lowering medication use. Among the components of MetS, high blood pressure (WHO definition), high waist circumference (using the national cutoff of ≥ 95 cm), and high glucose component by the JIS/IDF definitions remained independent predictors of SCD with HRs of 1.79 (1.29-2.48), 1.46 (1.07-2.00), and 1.52 (1.12-2.05), respectively., Conclusions: The constellation of MetS, except for when defined with ATP III definition, is a marker for identifying individuals at higher risk for SCD; however, not independent of its components. Among MetS components, abdominal obesity using the population-specific cutoff point, high glucose component (JIS/IDF definitions), and high blood pressure (WHO definition) were independent predictors of SCD., (© 2022. The Author(s).)

Background: We aimed to investigate the gender difference in the association between changes in metabolic syndrome (MetS) and its components with the risk of cardiovascular disease (CVD) and coronary heart disease (CHD) among adult participants in the Tehran lipid and glucose study cohort., Methods: A total of 4624 adults (aged ≥ 30 years) who participated in two Phases 2 (2002-2005) and 3 (2005-2008) were included and followed up until 2018. Based on the status of MetS and its components in two phases, we divided participants into four groups: MetS-free, MetS-developed, MetS-recovery and MetS-stable groups, and similar categories were defined for MetS components. Multiple Cox regression models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs), and women-to-men ratios of HRs (RHRs)., Results: During a median follow-up of 11.6 years, 619 CVD events (292 women) and 512 CHD events (230 women) occurred. In both genders, the MetS-stable group had the highest risk of CVD and CHD, compared with the MetS-free group, but the associations were stronger in women than men: the HR (95% CI) were (2.76, 2.00-3.82) and (3.08, 2.15-4.40) for CVD and CHD, respectively, in women, and (1.60, 1.23-2.09) and (1.74, 1.30-2.31) for men. The multivariate adjusted women-to-men RHRs were (1.72, 1.16-2.56) for CVD and (1.77, 1.14-2.73) for CHD. Only among women, the risks for CVD in MetS-recovery group (1.67, 1.06-2.63) and MetS-developed group (1.89, 1.16-3.06|) were higher than MetS-free group. For CHD, women in MetS-developed group (1.86, 1.07-3.22) had higher risk than MetS-free group. However, no evidence of gender difference was observed in these associations. Among MetS components, persistent high blood pressure (BP) conferred greater risk for CVD and CHD in women than men; the women-to-men RHRs of CVD and CHD for high BP-stable groups were 1.54 (1.05-2.26) and 1.62 (1.07-2.47), respectively. For CHD events, persistent high fasting plasma glucose was associated with greater risk in women than men with women-to-men RHRs of 1.62 (1.09-2.40)., Conclusion: Change in MetS and its key components were associated with different risks for CVD events in both genders, with generally stronger associations in women than men., (© 2022. The Author(s).)

Background and Aims: The association between obesity severity and duration with the transition from metabolically healthy obese/overweight (MHO) phenotype to metabolically unhealthy obese (MUO) phenotype is not well understood., Methods and Results: This study includes the Tehran Lipid and Glucose Study participants who were initially classed as MHO. Cumulative excess weight (CEW) and cumulative excess waist circumference (CEWC) scores, which represent the accumulation of body mass index and waist circumference deviations from expected values over time (kg/m 2 ∗ y and cm ∗ y, respectively), were calculated until the transition from MHO to MUO or the end of follow-up. The sex-stratified association of CEW and CWEC with the transition from MHO to MUO was investigated by time-dependent Cox models, adjusting for confounders. Out of 2525 participants, 1732 (68.5%) were women. During 15 years of follow-up, 1886 (74.6%) participants transitioned from MHO to MUO. A significant association was found between CEW and CEWC quartiles with the development of MUO among women participants (fully adjusted hazard ratios in the fourth quartile of CEW and CEWC [95% (CI)]:1.65 [1.37-1.98] and [95% CI]: 1.83 [1.53-2.19]). There was no significant association between CEW and CEWC with the MHO transition to MUO among men participants., Conclusion: Over 15 years of follow-up in TLGS, general and central obesity accumulation was associated with the increased transition from MHO to MUO among women participants. More research with a larger sample size is needed to confirm and explain why the results are different for men and women., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: There is limited evidence regarding the impact of pregnancy loss on the subsequent risk of metabolic disorders. We aimed to investigate whether history of pregnancy loss is associated with the subsequent risk of prediabetes (pre-DM), diabetes (DM), and metabolic syndrome (METs) among couples., Method: In this population-based cohort study, 2765 couples with and without history of pregnancy loss and free of DM, pre-DM, and METs at baseline were included and followed for incidents of DM, pre-DM, and METs by 3-year intervals visits from 1999 to 2018. Detailed data of variables was collected using standard questionnaires, interviews, clinical and laboratory assessments. A modified Poisson regression for binary outcome data with a log link function and robust error variance was used to estimate relative risks (RRs) in couples with and without history of pregnancy loss. Both unadjusted and adjusted models were fitted, and effect measures were calculated., Result: During a median follow-up of 15 years, females with history of pregnancy loss were experienced more pre-DM (50% vs. 45.5%), DM (28.9% vs. 21.3%), and METs (70% vs. 60.1%) than females without such history. Moreover, history of pregnancy loss increased the risk of METs by 8% among females. The incidence of DM in males with history of pregnancy loss in their spouses was higher than in males without it (28.8% vs. 23.5%). Among males, having a spouse with history of pregnancy loss was positively associated with the risk of pre-DM (RR = 1.12; 95%CI: 1.02, 1.23, p = 0.02); furthermore, they were more prone to the risk of METs than females with a history of pregnancy loss (RR = 1.13; 95%CI: 1.07, 1.20, p < 0.001)., Conclusion: Although pregnancy loss is a female-specific factor, may foreshadow the subsequent METs, our study identified a higher risk of subsequent pre-DM and METs in males with history of pregnancy loss in their spouses. Pregnancy loss could be considered a possible future risk factor for metabolic disorders in couples., (© 2022. The Author(s).)

Background: Metabolic syndrome (MetS) is a prevalent multifactorial disorder that can increase the risk of developing diabetes, cardiovascular diseases, and cancer. We aimed to compare different machine learning classification methods in predicting metabolic syndrome status as well as identifying influential genetic or environmental risk factors., Methods: This candidate gene study was conducted on 4756 eligible participants from the Tehran Cardio-metabolic Genetic study (TCGS). We compared predictive models using logistic regression (LR), Random Forest (RF), decision tree (DT), support vector machines (SVM), and discriminant analyses. Demographic and clinical features, as well as variables regarding common GCKR gene polymorphisms, were included in the models. We used a 10-repeated tenfold cross-validation to evaluate model performance., Results: 50.6% of participants had MetS. MetS was significantly associated with age, gender, schooling years, BMI, physical activity, rs780094, and rs780093 (P < 0.05) as indicated by LR. RF showed the best performance overall (AUC-ROC = 0.804, AUC-PR = 0.776, and Accuracy = 0.743) and indicated BMI, physical activity, and age to be the most influential model features. According to the DT, a person with BMI < 24 and physical activity < 8.8 possesses a 4% chance for MetS. In contrast, a person with BMI ≥ 25, physical activity < 2.7, and age ≥ 33, has 77% probability of suffering from MetS., Conclusion: Our findings indicated that, on average, machine learning models outperformed conventional statistical approaches for patient classification. These well-performing models may be used to develop future support systems that use a variety of data sources to identify persons at high risk of getting MetS., (© 2022. The Author(s).)

Aim: This study aimed to determine the association of urinary microalbumin concentrations with type 2 diabetes mellitus (T2DM), metabolic syndrome (MetS), and its phenotypes. The optimum cut-off values of urinary microalbumin and microalbumin-to-creatinine ratio (MCR) for predicting the chance of having T2DM and MetS were also defined., Methods: Adult men and women (n = 1192) participated in the sixth phase (2014-2017) of the Tehran Lipid and Glucose Study (TLGS), with completed data, were included in the analyses. Odds ratios (ORs) (and 95% confidence intervals (CIs)) of T2DM, MetS, and its components across tertile categories of urinary microalbumin concentrations were estimated using multivariable logistic regressions. The optimal cut-off points of urinary microalbumin and MCR were determined using the receiver operator characteristic (ROC) curve analysis., Results: Participants' mean (±SD) age was 44.9 (±14.0) years, and 44.6% of the participants were men. The prevalence of microalbuminuria was 14.4%. Chance of having T2DM was significantly higher in the highest tertile of urinary microalbumin concentration (OR = 2.29, 95% CI = 1.43-3.67) and MCR (OR = 1.82, 95% CI = 1.15-2.89). Subjects with the highest urinary microalbumin concentration were more likely to have MetS (OR = 1.66, 95% CI = 1.17-2.35), hypertension (OR = 1.63, 95% CI = 1.16-2.30) and hyperglycemia (OR = 1.78, 95% CI = 1.24-2.56). No significant association was observed between urinary microalbumin concentrations and other components of MetS. The optimal cut-off points of urinary microalbumin for predicting the chance of having T2DM and MetS were 14.0 and 13.6 mg/L, respectively., Conclusions: Elevated spot urinary microalbumin, below the values defined as microalbuminuria, was associated with the chance of having T2DM and MetS., (© 2022. The Author(s).)

Although an independent role for several important lifestyle factors in the aetiology of metabolic syndrome (MetS) has been established, less is known about their combined effects. We aimed to investigate the association of the combined role of recognised lifestyle factors, expressed as a healthy lifestyle score (HLS), and the risk of MetS in Tehranian adults. A total of 3480 participants without MetS were recruited from among participants of the Tehran Lipid and Glucose Study (2009-2011) and followed a mean of 6 years. Dietary data were collected using a validated food frequency questionnaire at baseline. We determined HLS in three ways among the participants based on four factors including, no current smoking, no obesity, vigorous physical activity and a healthy dietary pattern (assessed by either the alternate healthy eating index-2010 [AHEI-2010], the modified French Programme National Nutrition Santé-Guideline Score [mPNNS-GS] or the healthy diet pattern score [HDP]). All three indices consisted of the four factors including smoking (yes/no), physical activity (active/inactive), obesity (yes/no) and diet quality. Mean ± SD age of participants (43.5% men) was 38.7 ± 13.0 years. During the study follow-up, 558 (16.0%) new cases of MetS were identified. In the age- and sex-adjusted model, there was a negative relationship between the higher score of HLS-AHEI-2010 (OR = 0.42; 95% CI: 0.29-0.60), HLS-mPNNS-GS (OR = 0.45; 95% CI: 0.33-0.62) and HLS-HDP (OR = 0.70; 95% CI: 0.52-0.93) with the risk of MetS (p for trend <0.05). In the multivariable model, after adjustment for confounding variables, the risk of MetS decreased across tertiles of HLS-AHEI-2010 (OR = 0.48; 95% CI: 0.33-0.70, p for trend <0.001), HLS-mPNNS-GS (OR = 0.50; 95% CI: 0.36-0.69, p for trend <0.001) and HLS-HDP (OR = 0.67; 95% CI: 0.49-0.90, p for trend: 0.008). The findings of the current study highlight that greater adherence to modifiable healthy lifestyle factors scores is associated with a decreased risk of MetS., (© 2022 British Nutrition Foundation.)

Objectives: The aim of the present study was to evaluate the prevalence of polycystic ovary syndrome (PCOS), its phenotypical and cardio-metabolic features in a community sample of the Iranian population in comparison to healthy eumenorrheic, non-hirsute women without polycystic ovaries. The second aim was to assess the cardio-metabolic characteristics of women who suffered from one criteria of PCOS compared to those healthy eumenorrheic, non-hirsute women., Methods: In this cross-sectional population-based study, a total of 1,960 eligible women, aged (18-45 years) were recruited from the Tehran-Lipid and Glucose-Study participants and were classified as the three groups of (i) women with PCOS by the Rotterdam criteria, (ii) non-PCOS women with one criteria of PCOS and (iii) healthy eumenorrheic, non-hirsute women without polycystic ovaries morphology (PCOM) as the control group. Further PCOS women were extended to four phenotypes of hyperandrogenism, oligo-anovulation, polycystic ovaries (phenotype A), hyperandrogenism, oligo/anovulation (phenotype B), hyperandrogenism, polycystic ovaries (phenotype C) and oligo-anovulation, polycystic ovaries (phenotype D). Cardio-metabolic profiles and the prevalence of comorbidities of metabolic syndrome (MetS) and lipid abnormalities were compared among these groups linear, and the median regression models adjusted for age and body mass index., Results: The prevalence of PCOS according to the diagnostic criteria of the NIH, Rotterdam and AE-PCOS Society were 13.6, 19.4, and 17.8, respectively. Among those who met the Rotterdam criteria, 23.9, 46.3, 21.6, and 8.2% had phenotypes A, B, C, and D, respectively. Among the remaining 1,580 women who did not fulfil the PCOS criteria, 108 (6.8%) suffered from only oligo/anovulation, 332 (21%) only hyperandrogenism/hyperandrogenemia, 159 (16.2%) only PCOM in ultrasound and 981 (62%) were healthy eumenorrheic, non-hirsute women without PCOM. The study revealed that some adiposity indices and lipid abnormalities in PCOS phenotypes with hyperandrogenism (A, B, and C) were worse than in healthy women. By contrast, women with phenotype D did not differ from the healthy ones in terms of adiposity and lipid abnormalities. However, the respective values for other cardio-metabolic profiles and MetS rates in different phenotypes of PCOS were similar to the healthy women. Only the prevalence of MetS in phenotype A was significantly higher than in the healthy women. There were no statistically significant differences between participants with one criteria of PCOS and healthy counterparts in terms of most adiposity indexes, cardio-metabolic factors, and comorbidity of MetS and its components. However, women with hyperandrogenism had a significantly higher level of the waist to height ratio (WHtR) and hypertriglyceridemia than their healthy counterparts., Conclusion: PCOS, mainly classical phenotypes A and B, are common among Iranian women of reproductive age. Women with PCOS who had androgen excess exhibited the worst lipid profile, and those who had full three criteria of the syndrome exhibited the higher rate of MetS. However, women with only ovulatory dysfunction and only PCOM had similar cardio-metabolic characteristics, compared to healthy subjects. These data suggest that routine screening for metabolic disturbances may be needed in the prevention of cardio-metabolic disorders in patients with more serious phenotypes of PCOS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Farhadi-Azar, Behboudi-Gandevani, Rahmati, Mahboobifard, Khalili Pouya, Ramezani Tehrani and Azizi.)

Background: The clinical significance of metabolic syndrome (MetS) during adolescence and its association with adulthood adverse outcomes is a controversial issue. This study aimed to investigate the association of MetS and metabolic phenotypes with a high carotid intima-media thickness (CIMT) in early adulthood., Methods: MetS was defined as proposed by Cook, de Ferranti, the National Cholesterol Education Program (NCEP), and the pediatric International Diabetes Federation (IDF). Metabolic phenotypes were defined based on the binary clustering of cardiovascular risk factors. The participants were adolescent's individual selected from a large cohort study and followed for 18.2 years. Multivariate-adjusted odds ratios (ORs) were calculated for a high CIMT incidence (≥95th percentile)., Results: In this study, 862 adolescents (52.3% males), with the mean age of 13.4 ± 2.2 years, were included. The presence of MetS, based on the definitions proposed by Cook (OR = 1.90, 95% CI: 1.01-3.57, P = 0.046) and de Ferranti (OR = 1.74; 95% CI: 1.04-2.90, P = 0.033), was associated with the increased risk of a high CIMT in early adulthood. Metabolic phenotypes, including high waist circumference (WC)/hypertension (HTN), high WC/low high-density lipoprotein-cholesterol (HDL-C), and high triglyceride (TG)/high WC, showed higher risks of a high CIMT. However, these positive associations become insignificant after adjusting for the adulthood BMI, except for the high WC/low HDL-C phenotype (OR = 2.04, 95% CI: 1.02-4.11, P = 0.044)., Conclusion: The high WC/low HDL-C phenotype had a better predictive value and could be used as a simpler alternative for MetS to identify adolescents with a higher risk of high CIMT during early adulthood., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study aimed to evaluate the association between the intake of total flavonoids and flavonoid subclasses and metabolic syndrome (MetS) risk and to assess the modulating effects of lifestyle factors on these associations. A total of 1915 participants from the Tehran Lipid and Glucose Study were followed-up during 2006-2008 and 2016-2018. Their dietary intake was assessed by a food frequency questionnaire at baseline and within three-year intervals afterward. Moreover, the modifying effect of weight gain on the association between total flavonoids and MetS was assessed by Cox regression analysis. Participants in the highest tertile of flavonoid, flavonol, and flavone had a significantly lower MetS risk as compared to those in the lowest tertile. Also, in participants with weight gain <7%, all flavonoid subclasses had a more pronounced risk-reducing effect. Overall, the total flavonoid, flavonol, and flavone reduced the risk of MetS; this association could be modified by weight gain.

Context: Recently, reduced sensitivity to thyroid hormone as a more common finding in the general population and its possible association with metabolic parameters has been the focus of attention., Objective: The objective was to evaluate the cross-sectional association of thyroid hormone sensitivity with diabetes, metabolic syndrome (MetS), and its components., Methods: The study included a Tehranian representative sample of 5124 subjects aged ≥20 years participating in the Tehran Thyroid Study (2008-2011). Body weight, waist circumference, and blood pressure (BP) were measured, and serum concentrations of lipids and lipoproteins, fasting blood glucose, insulin, free thyroxine (fT4), and thyrotropin (TSH) were assayed. Thyroid hormone resistance was calculated by the Thyroid Feedback Quantile-based Index (TFQI) and Iranian-referenced Parametric TFQI (PTFQI) and compared with 2 other indices: Thyrotroph T4 Resistance Index (TT4RI) and TSH Index., Results: TFQI was significantly associated with high BP MetS criterion (OR = 1.14, 95% CI: 1.06, 1.23) and diabetes mellitus (OR = 1.16, 95% CI: 1.04, 1. 30, P = .009) in euthyroid subjects after adjusting for age, sex, smoking, physical activity, body mass index, and Homeostasis Model Assessment Index for Insulin Resistance. TFQI was not associated with new-onset diabetes contrary to known diabetes in subgroup analysis. The results were similar for PTFQI. TSHI (OR = 1.22, 95% CI: 1.08, 1.38, P = .001) and TT4RI (OR = 1.08, 95% CI: 1.01, 1.16, P < .001) were associated only with high BP in euthyroid subjects., Conclusion: The new TFQI index seems to be the indicator of reduced sensitivity to thyroid hormone most suitable to associate its population variations with diabetes and hypertension in euthyroid subjects; however, interpretation for diabetes should be concerned with cautions, necessitating future studies., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Over the past few years, obesity and metabolic syndrome prevalence among children and adolescence have an increasing trend. This study aims to investigate the association of obesity phenotypes during childhood and adolescence with early adulthood carotid intima-media thickness (CIMT)., Methods and Results: Participants were divided into four obesity phenotypes: Metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Participants were followed for 18 years. Multivariate-adjusted Risk Ratios (RRs) were calculated for high CIMT (≥95% percentile) incidence. In this cohort study 1220 children and adolescents with the average age of 10.9 ± 4.0 years were included. CIMT values had a significantly increasing trend from MHNW to MUO group (p for trend<0.001). Individuals with normal weight status, even with an unhealthy metabolic profile did not have higher risk of high CIMT. Similarly, Children with obesity but healthy metabolic status was not at higher risk. On the other hand, MUO phenotype during childhood was associated with increased risk of high CIMT in early adulthood (RR = 2.13, 95%CI (1.02-4.48)). This association became insignificant for all obesity phenotypes after adjusting for adulthood BMI., Conclusion: Adulthood CIMT has an increasing trend based on childhood and adolescence obesity phenotypes from MHNW to MUO. Children with MUO phenotype was the only ones that had an increased risk of high CIMT incidence in early adulthood., Competing Interests: Declaration of competing interest 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 © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Individuals with transition from metabolically healthy overweight/obese (MHO) to metabolically unhealthy overweight/obese (MUO) phenotype are significantly predisposed to greater risks of cardiovascular events compared to those with a persistent MHO phenotype. The aim of this study was to evaluate the predictive performance of wrist circumference for this transition in adults over a 15.5-year follow-up., Methods: We included 309 males and 821 females with the age of ≥18 years old, body mass index ≥25 kg/m 2 , and metabolically healthy status according to the criteria of the Joint Interim Statement. The incidence of MUO phenotype was evaluated for each gender, across tertiles wrist circumference, using Cox-proportional hazard models., Results: The overall rate of transition from MHO to MUO phenotype was 87.1% in males and 77.5% in females. The hazard ratios (HRs) with 95% CI across second and third tertiles of wrist circumference were 0.89 (0.64-1.24) and 1.31 (0.99-1.73) in men (P for trend =0.027); and 1.34 (1.09-1.66) and 1.61 (1.30-2.00) in women (P for trend <0.001), respectively. After multivariable adjustment, HRs across second and third tertiles of wrist circumference were 0.92 (0.64-1.32) and 1.18 (0.83-1.67) in males (p for trend =0.352), and 1.32 (1.05-1.65) and 1.34 (1.06-1.96) in females (p for trend =0.025), respectively., Conclusions: Wrist circumference significantly predicts the transition from MHO to MUO phenotype in adults of both genders. However, it is an independent predictor of the transition only in females. Future studies are warranted to clarify the role of wrist circumference mechanisms on metabolic risk deterioration., (© 2021. The Author(s).)

Background: Markov system dynamic (MSD) model has rarely been used in medical studies. The aim of this study was to evaluate the performance of MSD model in prediction of metabolic syndrome (MetS) natural history., Methods: Data gathered by Tehran Lipid & Glucose Study (TLGS) over a 16-year period from a cohort of 12,882 people was used to conduct the analyses. First, transition probabilities (TPs) between 12 components of MetS by Markov as well as control and failure rates of relevant interventions were calculated. Then, the risk of developing each component by 2036 was predicted once by a Markov model and then by a MSD model. Finally, the two models were validated and compared to assess their performance and advantages by using mean differences, mean SE of matrices, fit of the graphs, and Kolmogorov-Smirnov two-sample test as well as R 2 index as model fitting index., Results: Both Markov and MSD models were shown to be adequate for prediction of MetS trends. But the MSD model predictions were closer to the real trends when comparing the output graphs. The MSD model was also, comparatively speaking, more successful in the assessment of mean differences (less overestimation) and SE of the general matrix. Moreover, the Kolmogorov-Smirnov two-sample showed that the MSD model produced equal distributions of real and predicted samples (p = 0.808 for MSD model and p = 0.023 for Markov model). Finally, R 2 for the MSD model was higher than Markov model (73% for the Markov model and 85% for the MSD model)., Conclusion: The MSD model showed a more realistic natural history than the Markov model which highlights the importance of paying attention to this method in therapeutic and preventive procedures., (© 2021. The Author(s).)

Background: Evidence of possible beneficial effects of dietary diabetes risk reduction score (DDRRS) on reducing the risk of various chronic diseases such as metabolic syndrome (MetS) are limited. This is a prospective, population-based cohort study, which aimed to investigate the relationship of the DDRRS and its components with MetS incident in Iranian adults., Methods: Individuals without MetS (n=3561) were recruited from participants of the Tehran Lipid and Glucose Study (2009-2011) and followed for a mean of 6.01 years. A validated food frequency questionnaire was used to determine the DDRRS using based on eight components, including higher intakes of cereal fiber, nuts, coffee, and polyunsaturated: saturated fat ratio and lower intakes of red or processed meats, sugar-sweetened beverages, trans fatty acids, and low glycemic index. We used the multivariable logistic regression analysis to determine the odds ratio (ORs) and 95 % confidence interval (CI) of MetS across the tertiles of DDRRS., Results: The mean (SD) age of individuals was 38.1(12.6) years at baseline. Median (25-75 interquartile range) DDRRS for all participants was 20(18-22). During the study follow-up, 682(19.1 %) new cases of MetS were reported. Based on the age and sex-adjusted model, participants in highest tertile of DDRRS had lower risk of MetS in compared with the lowest one (OR=0.64;95 %CI:0.52-0.79, P for trend=0.001). In the multivariable adjusted model, after adjustment for all possible confounding variables, the risk of MetS is decreased across tertiles of DDRRS (OR=0.60;95 %CI:0.48-0.75, P for trend=0.001). Also, higher scores of some DDRRS components including red and processed meat, sugar sweetened beverages, and coffee were related to decreased incidence of MetS., Conclusions: The results of this study revealed that greater adherence to DDRRS can be associated with decreased risk of MetS in Iranian adult., (© 2021. The Author(s).)

Background & Aims: This study aimed to determine the prospective relationship between the consumption of sugar-sweetened beverages (SSBs) and 100% fruit juice and metabolic syndrome (MetS) and to investigate whether weight change can modify this association in a representative sample of the population of Tehran, Iran., Methods: In this 8.9-year follow-up study, the consumption of SSBs and 100% fruit juice by 1915 individuals, who participated in Tehran Lipid and Glucose Study (TLGS), was examined using a validated food frequency questionnaire. The MetS was defined according to the Joint Interim Statement. Participants were categorized as those who lost weight (≥-2%), those with weight stability (-1.9%-1.9%), and those who gained weight (≥2%). The Cox regression model was used to determine the relationship between the consumption of SSBs and 100% fruit juice and the risk of MetS and weight gain ≥2%. Also, the modifying effect of weight change including weight loss, weight stability and weight gain on the relationship between SSBs and 100% fruit juice consumption and the incidence of MetS was assessed., Results: There was no significant association between the consumption of SSBs and the risk of MetS in the crude model; however, after adjustments for confounders, a significant positive association was found between the consumption of SSBs and the risk of MetS (HR: 1.33; 95% CI: 1.07-1.66). Also, no significant association was observed between the consumption of 100% fruit juice and the risk of MetS in the crude model. However, after adjustments for the potential confounders, 100% fruit juice was inversely associated with the MetS risk (HR: 0.78; 95% CI: 0.63-0.95). The consumption of SSBs and 100% fruit juice was positively associated with weight gain (≥2% during the follow-up). Nevertheless, after adjustments for lifestyle and dietary factors, there was no significant association between the consumption of SSBs and weight gain. On the other hand, the consumption of 100% fruit juice was positively associated with the increased risk of weight gain (HR: 1.41; 95% CI: 1.20-1.65). Among participants with weight loss, the first, second and third tertiles of 100% fruit juice reduced the risk of MetS by 29% (HR: 0.71; 95% CI: 0.51-0.99), 47% (HR: 0.53; 95% CI: 0.37-0.75) and 35% (HR: 0.65; 95% CI: 0.46-0.92), respectively., Conclusion: Although 100% fruit juice reduced the risk of MetS, its consumption must be limited due to its positive effect on weight gain. On the other hand, the consumption of 100% fruit juice reduced the risk of MetS, depending on the individual's weight change. Also, high consumption of SSBs was associated with the incidence of MetS., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Metabolic syndrome (MetS), a major contributor to cardiovascular disease and diabetes, is considered to be among the most common public health problems worldwide., Objective: We aimed to identify and rank the most important nutritional and nonnutritional factors contributing to the development of MetS using a data-mining method., Methods: This prospective study was performed on 3048 adults (aged ≥20 years) who participated in the fifth follow-up examination of the Tehran Lipid and Glucose Study, who were followed for 3 years. MetS was defined according to the modified definition of the National Cholesterol Education Program/Adult Treatment Panel III. The importance of variables was obtained by the training set using the random forest model for determining factors with the greatest contribution to developing MetS., Results: Among the 3048 participants, 701 (22.9%) developed MetS during the study period. The mean age of the participants was 44.3 years (SD 11.8). The total incidence rate of MetS was 229.9 (95% CI 278.6-322.9) per 1000 person-years and the mean follow-up time was 40.5 months (SD 7.3). The incidence of MetS was significantly (P<.001) higher in men than in women (27% vs 20%). Those affected by MetS were older, married, had diabetes, with lower levels of education, and had a higher BMI (P<.001). The percentage of hospitalized patients was higher among those with MetS than among healthy people, although this difference was only statistically significant in women (P=.02). Based on the variable importance and multiple logistic regression analyses, the most important determinants of MetS were identified as history of diabetes (odds ratio [OR] 6.3, 95% CI 3.9-10.2, P<.001), BMI (OR 1.2, 95% CI 1.0-1.2, P<.001), age (OR 1.0, 95% CI 1.0-1.03, P<.001), female gender (OR 0.5, 95% CI 0.38-0.63, P<.001), and dietary monounsaturated fatty acid (OR 0.97, 95% CI 0.94-0.99, P=.04)., Conclusions: Based on our findings, the incidence rate of MetS was significantly higher in men than in women in Tehran. The most important determinants of MetS were history of diabetes, high BMI, older age, male gender, and low dietary monounsaturated fatty acid intake., (©Firoozeh Hosseini-Esfahani, Behnaz Alafchi, Zahra Cheraghi, Amin Doosti-Irani, Parvin Mirmiran, Davood Khalili, Fereidoun Azizi. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 02.09.2021.)

Background: Intake of snack foods has been previously associated with an elevated risk of chronic disease; however, studies on snack foods and metabolic syndrome (MetS) while considering the modifying effect of socioeconomic status (SES) and lifestyle factors on this association are lacking. We aimed to investigate the association between snack foods intake and the MetS risk, and the mediatory effects of SES and lifestyle factors on the forenamed association among adults who participated in the Tehran Lipid and Glucose Study (2006-2018)., Methods: This is a prospective study of 1915 participants (male, 40.5%), aged 19-74 year who were free of MetS at baseline. Dietary intakes were gathered using a validated, semi-quantitative food frequency questionnaire at baseline (2006-2008), and with 3-year intervals afterwards. Alternative approach was used for snack foods from all available questionnaires during follow-up. Snack foods were divided into 4 categories, including total snacks, biscuits and cakes, candies and chocolate, and salty snacks. Total snack foods intake and its subgroup (serving/week) were modeled as tertiles. MetS was diagnosed according to the Joint Interim Statement criteria. Physical activity level (PAL) categorized as low/medium and high levels. Information regarding smoking (Smoker/Non-smoker), education (higher/lower education), and occupation (employed/non-employed) was gathered using questionnaire. The Cox regression was used, regarding interaction between snack foods, SES, and PAL on the MetS risk., Results: A total of 591 incident MetS cases were diagnosed during 8.9 years of follow-up. The median total snack foods intake was 5.2 serving/week (IQR: 3.0-9.1). Total snack foods intake was positively associated with the MetS risk after adjusting for potential confounders (adjusted for age and gender, energy intake, total fiber intake, smoking status, PAL, education levels, family history of diabetes, family history of CVD events, and BMI). After adjustment for confounders, among snacks' subgroups, candies and chocolate intake was positively associated with MetS risk. Moreover, among lower-educated and non-employed participants, candies and chocolate intake was positively associated with the MetS risk, by 38 and 43% respectively. Stratification based on PAL resulted a positive association between intake of total snack foods and candies and chocolates and risk of MetS among participants with low PAL., Conclusion: Snack foods, especially candies and chocolate, increased the risk of MetS, among individuals with a low PAL., (© 2021. The Author(s).)

Background: The prevalence of metabolic syndrome (MetS) is rapidly increasing in the world; also, the importance of management of MetS to decrease the risk of cardiovascular disease (CVD) has been recognized worldwide. This study aimed to explore the clusters of participants based on MetS components and its association with CVD outcomes., Methods: We included 2598 middle-aged participants (1545 women and 1053 men), 45-65 years old, at baseline and without prior CVD history. Participants were followed up for 10years. We conducted a latent class analysis based on MetS components. Subsequently, the relationship between latent classes and the incidence of CVD was investigated using Cox regression models adjusted for the main confounders., Results: During the study period, 393 (186 women and 207 men) new cases of CVD were identified among participants. In both genders, four distinct latent classes were identified: (1) Mets class (its prevalence rate in men: 19.6%, women: 27.7%), (2) Hypertension class (men: 12.1%, women: 13.7%), (3) Dyslipidemia class (men: 31.7%, women: 30.7%), (4) Low risk class (men: 39.3%, women: 30.5%). Compared with low-risk class, in both genders, Mets and hypertension classes were significant predictors of incident CVD. However, dyslipidemia class was a significant predictor just in women., Conclusion: We found four subclasses in both genders indicating the same patterns of MetS latent classes in men and women. However, the relationship between subclasses of MetS and incident CVD varied by gender. These results suggest that the etiology of MetS involve more than one pathway and giving equal weight to each component or using the same cut-off values in both genders need to be reconsidered., Competing Interests: Declaration of competing interest There are no competing interests concerning the publication of the current article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background & Aims: The aim of this study was to evaluate the association of nut consumption and its various types with metabolic syndrome (MetS) risk and to investigate whether lifestyle factors (physical activity and smoking status) and socioeconomic status (education and occupation) modulate the association of nut consumption and the risk of MetS., Methods: We prospectively studied 1915 participants of the Tehran Lipid and Glucose study, among whom 591 were diagnosed with MetS during 8.9 years of follow-up. Nut consumption and its various types were assessed using a validated semi-quantitative food frequency questionnaire. Multivariable adjusted Cox regression was used to estimate Hazard Ratios (HRs) for MetS events across tertiles of nut consumption and its various types. Regarding interaction between nut consumption and physical activity levels, education levels, and smoking status on the risk of MetS, using joint classification, the effect modification of lifestyle factors and socioeconomic status on the association between nut consumption (

Metabolic syndrome (MetS) is one of the most important risk factors for cardiovascular disease. The 11p23.3 chromosomal region plays a potential role in the pathogenesis of MetS. The present study aimed to assess the association between 18 single nucleotide polymorphisms (SNPs) located at the BUD13, ZPR1, and APOA5 genes with MetS in the Tehran Cardio-metabolic Genetics Study (TCGS). In 5421 MetS affected and non-affected participants, we analyzed the data using two models. The first model (MetS model) examined SNPs' association with MetS. The second model (HTg-MetS Model) examined the association of SNPs with MetS affection participants who had a high plasma triglyceride (TG). The four-gamete rules were used to make SNP sets from correlated nearby SNPs. The kernel machine regression models and single SNP regression evaluated the association between SNP sets and MetS. The kernel machine results showed two sets over three sets of correlated SNPs have a significant joint effect on both models (p < 0.0001). Also, single SNP regression results showed that the odds ratios (ORs) for both models are almost similar; however, the p-values had slightly higher significance levels in the HTg-MetS model. The strongest ORs in the HTg-MetS model belonged to the G allele in rs2266788 (MetS: OR = 1.3, p = 3.6 × 10 -7 ; HTg-MetS: OR = 1.4, p = 2.3 × 10 -11 ) and the T allele in rs651821 (MetS: OR = 1.3, p = 2.8 × 10 -7 ; HTg-MetS: OR = 1.4, p = 3.6 × 10 -11 ). In the present study, the kernel machine regression models could help assess the association between the BUD13, ZPR1, and APOA5 gene variants (11p23.3 region) with lipid-related traits in MetS and MetS affected with high TG.

Context: The relationship between metabolic syndrome (MetS) and the risk of fracture is a matter of debate., Objective: This work aimed to determine the impact of MetS and its components on the risk of hospitalized fractures, during a median follow-up of 15.9 years., Methods: A total of 7,520 participants (4,068 women) 30 years or older entered the study. Multivariable Cox proportional hazards regression were applied for data analysis., Results: The prevalence of MetS was 40.0% and 40.4% in men and women, respectively. During the follow-up, hospitalized fracture was observed in 305 cases (men = 152). The multivariable hazard ratio (HR) and 95% confidence interval (CI) of MetS for incident fracture for men and women was 0.72 (0.49-1.05, P = .08) and 1.38 (0.96-1.98, P = .08), respectively. In the fully adjusted model, high fasting plasma glucose (FPG) among men tended to be associated with a lower risk of fracture [0.67 (0.44-1.02, P = .06)]; among women, high waist circumference (WC) was associated with a greater risk [2.40 (1.55-3.73)]. Among the population 50 years and older in the pooled sample, MetS was not accompanied by the risk of fracture, but high WC was associated with a higher risk [1.58 (1.07-2.33)]. For incident hip/pelvic fracture, abdominal obesity-but not MetS per se-was also a strong and independent risk factor., Conclusion: A significant sex difference in the association between MetS and its components with incident fracture was observed. Women with central adiposity were at increased risk of hospitalized fracture, whereas men with high FPG were at decreased risk., (Published by Oxford University Press on behalf of the Endocrine Society 2021.)

Aims: This cohort study examined the association of total and individual dairy products with the risk of incident MetS and its components in children and adolescents., Methods: We prospectively assessed 531 participants aged 6-18 years without the MetS at baseline during an average 6.6-year follow-up period. Dairy consumption was estimated with a valid and reliable food frequency questionnaire. The MetS was defined according to the Cook criteria. The multivariable regression model was used to calculate the odds ratio (OR) for incident MetS associated with the consumption of dairy products., Results: The incidence of MetS was 9.8% after an average 6.6-year follow-up. After adjusting for potential confounders, OR (95% confidence interval) for incident MetS was 0.48 (0.23-1.00) for total dairy, 0.44 (0.21-0.92) for low-fat dairy, 0.46 (0.22-0.98) for low-fat milk, and 0.45 (0.21-0.97) for low-fat yogurt when comparing participants in the highest versus lowest tertile. A moderate intake of regular cheese was associated with decreased risk of MetS (OR = 0.43, 95% CI: 0.19-0.97). Replacing one serving/day of total dairy with nuts was associated with a lower (OR: 0.63, 95% CI: 0.42-0.95), whereas replacement by red and processed meat was associated with higher (OR: 1.55, 95%CI: 1.21-1.97) MetS risk. No significant association was found between high-fat dairy and MetS risk., Conclusions: Higher consumption of dairy products, particularly low-fat milk and yogurt, was associated with reduced risk of incident MetS, suggesting the capability of low-fat dairy products in the primary prevention of MetS in children and adolescents.

Obesity is the most crucial phenotype in metabolic syndrome (MetS), and waist circumference (WC) and body mass index (BMI) are two common indexes to define obesity. It is an accepted fact that genetic and environmental interaction influence obesity and MetS. Microsatellites are a subcategory of tandem repeats with a length of 1 to 10 nucleotides. Tandem repeats make up repetitive genomic regions. Differences in the number of tandem repeats or their variation (alleles) result in microsatellite polymorphisms. Thus, we attempted to find microsatellite variation associated with WC and BMI in a family-based study. Twelve microsatellite markers were selected to investigate possible genes or chromosomal regions in 91 families with at least one affected MetS. The cut-off values for BMI and WC were considered 25 kg/m 2 and 90 cm, respectively. In all members of the families, the strongest association was observed between the marker D11S1304 (allele 1) with both WC and BMI, independently, by the biallelic model in the family-based association test analysis (P < 0.05). Besides, when we compared high- and low-level groups in members with MetS, the markers D8S1743 and D11S1304 (allele 1) showed a strong association with WC (P = 0.0080) and BMI (P = 0.0074), respectively. When the simultaneous detection of the high WC and MetS status was used as a trait, the strongest association was observed with the marker D8S1743 (P = 0.0034). Moreover, when BMI with the high MetS status was used as a trait, the strongest association was observed with the marker D8S1743 (allele 4) (P = 0.0034). The obtained results showed a relationship between obesity and MetS with markers on the selected regions on chromosomes 8 and 11, and to a lesser degree, on chromosome 12.

Background: Careful evaluation of the progression trend of the metabolic syndrome (MetS) in children and adolescents (C&A) is one of the important methods of studying the natural history of MetS in them. This study was performed to determine the trend of changes in the progression of MetS from its components., Methods: This was a longitudinal study which was performed on data from 4 follow-up periods of Tehran Lipid and Glucose Study (TLGS) between 1999 and 2015. The research population consisted of 6-18-year-old children and adolescents creating 3895-person population. The criteria for the diagnosis of MetS was joint interim statement (JIS). The considered components were central adiposity, high blood pressure, insulin resistance, and dyslipidemia., Results: In this study, in the long term, the highest increase in the MetS' incidence in boys occurred in obesity and in girls in dyslipidemia and in total mode, in obesity. But in the short term (3.6 year follow-up periods) in the first to fourth periods, in total mode, the highest incidence occurred in dyslipidemia, hyperglycemia, dyslipidemia, and obesity. In terms of trend, in total mode, the highest increase in MetS incidence was related to the obesity component. Also, the incidence of MetS from all components was declining in overall mode. Also, the most common components at the beginning and end of the study in all groups were dyslipidemia with a decreasing and obesity with an increasing trend, respectively., Conclusion: It seems that in Iranian C&As, obesity and dyslipidemia components play a more important role in the further development of the MetS than other components. This matter requires careful and serious attention in preventive and control planning., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Diabetes India. All rights reserved.)

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.

Obese individuals can be categorized as "healthy obese" (MHO) and "unhealthy obese" (MUO) based on the presence or absence of metabolic abnormality. This study sets out to assess potential genetic causes behind persistence of healthy metabolic status in individuals categorized as "healthy obese". This study was conducted in the framework of the Tehran cardio-metabolic genetic study (TCGS). 766 MHO subjects at the start of the study followed up 15 years for occurrence of metabolic unhealthy status. These two groups (persistent MHO, MUO) were compared regarding the presence or absence of 16 single nucleotide polymorphisms (SNPs) identified as being associated with obesity phenotype in previous studies. We used logistic regression model for assessing the association between MHO/MUO with candidate SNPs. By the end of the follow up, 206 (27%) were categorized as the persistent MHO and 560 (73%) as MUO groups. Considering interaction effect between some SNP and sex, a sex stratification analysis was applied. When the analysis was performed by gender, rs1121980 associated with a decrease, and rs7903146 with an increase in the likelihood of persistent MHO individuals. Another analysis was separately performed on postmenopausal women from both groups; it showed that rs13107325 was associated with an increase in the likelihood of persistent MHO status in this subgroup of woman. In all cases, the markers had dominant inheritance. This findings suggest that the expression of some genetic markers are associated with persistence of healthy metabolic status, in female obese individuals.

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

Background and Aims: The aim of this study is to investigate the association between the identified patterns of fruits and vegetables and metabolic syndrome (MetS) incidence, and to investigate whether lifestyle factors and socioeconomic status modify the effect of the patterns on MetS risk., Methods and Results: We prospectively studied 1915 participants of the Tehran Lipid and Glucose Study, who were aged 19-74 years and followed up for dietary assessment using a validated, semi-quantitative food frequency questionnaire. After adjustment for confounding factors, total vegetable intake was inversely related to the risk of MetS. Total fruit and total fruit and vegetable were not associated with MetS risk. We identified four major patterns of fruits and vegetables by factor analysis: "fresh fruit pattern", "vegetable pattern", "dried fruit and cruciferous vegetable pattern", and "potatoes and fruit juice pattern". "Vegetable pattern" was negatively associated with MetS risk, and "potatoes and fruit juice pattern" increased the risk of MetS. Among participants with weight gain <7% during follow-up, all four identified patterns reduced MetS risk. When stratified by smoking, "vegetable pattern" and "dried Fruit and cruciferous vegetable pattern" lowered MetS risk among non-smokers. Stratification based on education resulted in MetS risk reduction across tertiles of "fresh fruit pattern" and "vegetable pattern". First and second tertiles of "dried fruit and cruciferous vegetable pattern" lowered MetS risk among educated participants, compared to the reference., Conclusions: The reduction in MetS risk caused by fruits and vegetables intake depends on the modifying effect of lifestyle and socioeconomic factors., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Aims: The aim of this study was to investigate whether both weight change and the background intakes of macronutrient modulate the association between dietary branch chain amino acids (BCAAs) and the risk of metabolic syndrome (MetS)., Methods: This prospective study was conducted within the framework of theTehranLipidand Glucose Study. BCAA intakes were collected using a valid and reliable semi-quantitative food frequency questionnaire. MetS components were defined according to the modified national Cholesterol Education Program Adult Treatment Panel III. Weight change was categorized as weight gain (≥ or <7% over 8.9 year follow-up). Dietary fat and carbohydrate intake were categorized as above/below the median intake., Results: Among participants with weight gain ≥ 7% during follow-up, intakes of both dietary BCAAs and its various sources (below or above the median intake) were associated with higher risk of MetS, compared with subjects with lower intakes of BCAAs and weight change ≤ 7%. Background dietary fat and carbohydrate did not modify the association of dietary BCAAs and its various sources with the risk of MetS., Conclusions: Weight change, but not dietary macronutrient intake, modulates the association between dietary BCAAs and risk of MetS among adults., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Obesity phenotypes can be regarded as an indicator of CVD risk factors. The aim of the present study was to determine the prevalence of adolescents with different obesity phenotypes and the role of obesity phenotypes in prediction of the metabolic syndrome (MetS) in adults. For this population-based cohort study, 2159 adolescents aged 11-18 years were included. Subjects were divided into four obesity phenotype groups: metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW) and metabolically unhealthy obese (MUO). Cox proportional hazard modelling was used to estimate the incidence of the MetS in adults after a median follow-up of 11·3 years. The incidence rate of the MetS in early adulthood was 111·6 (95 % CI 98·7, 126·3) per 10 000 person-years, with higher values in boys (210·1 (95 % CI 183·0, 241·3)), compared with girls (39·7 (95 % CI 30·2, 52·1)). In the age- and adult BMI-adjusted model, the hazard ratio of the MetS in adulthood for boys was 3·33 (95 % CI 2·08, 5·32) among MUO phenotype followed less than 6 years, 1·71 (95 % CI 1·01, 2·90) among MHO, and 2·52 (95 % CI 1·72, 3·68) among MUNW. All associations were attenuated in girls except for MUO phenotype followed less than 6 years (5·72 (95 % CI 2·14, 15·3)). In conclusion, MUNW and MHO phenotypes in boys, but not in girls, and MUO phenotype in both sexes with less than 6 years of follow-up increased the risk of adult MetS compared with MHNW. It seems that lack of obesity at least in boys does not protect them from MetS development in adulthood.

Background: The optimal dietary pattern for reducing the extent of metabolic syndrome (MetS) has not been well established yet. The aim of this study was to evaluate dietary patterns and adherence to WHO healthy diet in children and adolescents and their associations with MetS., Methods: Subjects of this cohort study were selected from among children and adolescents of the Tehran Lipid and Glucose Study participants, aged 6-18 years (n = 424). Dietary measurements were collected using a valid and reliable food frequency questionnaire. MetS was defined as the existence of at least 3 risk factors according to the Cook criteria. Diet was assessed based on dietary components of the WHO healthy diet. Dietary patterns were defined by principal component analysis., Results: The mean ± SD age of participants (42% boys and 57% girls) was 13.5 ± 3.7 years. The most consistency with the WHO healthy diet was observed for cholesterol, free sugar and protein consumption in both genders, and the least was for n-3 poly-unsaturated fatty acid, trans-fatty acid and salt. Intake of SFA up to 12% of energy intake (third quartile) reduced the risk of MetS, compared to the first quartile. Subjects in the third quartile of n-6 poly-unsaturated fatty acid intake (6.2% of energy) showed the lowest odds ratio of MetS compared to the first quartile (OR: 0.18, CI: 0.04-0.66). In the adjusted model, the risk of MetS reduced across quartiles of MUFA intake by 60% (OR: 1, 0.40, 0.40, 0.42; P trend = 0.05). No significant trends were observed in the risk of MetS components across quartiles of the WHO healthy diet components. Three major dietary patterns were identified, the healthy, unhealthy and cereal/meat. An increased risk of MetS was observed in the highest quartile of unhealthy dietary pattern score compared to the lowest quartile (OR: 1, 0.81, 0.93, 2.49; P trend = 0.03)., Conclusions: Our results demonstrated that the majority of our population did not meet some components of WHO healthy diet recommendations. The quality and quantity of fatty acid intakes were associated with risk of MetS. Adherence to unhealthy dietary pattern was associated with two-fold increase in MetS risk.