Publications by authors named "Fereidoun Azizi"

913 Publications

Incidence of Thyroid Dysfunction Facing Metabolic Syndrome: A Prospective Comparative Study with 9 Years of Follow-Up.

Eur Thyroid J 2021 Jul 27;10(5):390-398. Epub 2021 Jan 27.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Studies assessing thyroid hormones in metabolic syndrome (MetS) patients are contradictory. Also, the effect of MetS on thyroid function over time is not yet evaluated. This study investigated the prevalence and incidence of thyroid dysfunction (TD) as well as time trends of thyroid hormones in subjects with and without MetS, during a 10-year follow-up in Tehranian adult population.

Methods: This is a prospective cohort study conducted in the framework of Tehran Thyroid Study on 5,786 subjects aged ≥20 years: 4,905 eligible participants entered the study after excluding those with corticosteroid or radioactive iodine use, pregnancy, thyrotropin (TSH) <0.1 and >10 mU/L, and missing data. Physical examinations were performed and serum concentrations of TSH, free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), fasting plasma glucose, insulin, and lipid profile were assessed at baseline and 3-year intervals during the follow-up. MetS was defined according to the Joint Interim Statement Definition.

Results: At baseline, there were no difference in median serum concentrations of FT4 and TSH between MetS and non-MetS group after adjusting for age, sex, BMI, smoking, and TPOAb positivity. Although there was higher risk of overt (42%) and subclinical hypothyroidism (16%) in MetS compared with non-MetS subjects, no significant difference was observed in adjusted ORs for any TD between 2 groups. There were also no significant differences in time trends of TSH, FT4, TPOAb positivity, and incidence rates of TDs between MetS and non-MetS groups during 10 years, after adjustment for age, sex, BMI, smoking status, and TPOAb positivity.

Conclusion: MetS is not associated with thyroid hypofunction considering other important confounders such as age, sex, smoking, BMI, and TPOAb positivity. There is also no difference in the trend of thyroid hormones and incidence of TD between MetS and non-MetS subjects during a 10-year follow-up.
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http://dx.doi.org/10.1159/000512665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406240PMC
July 2021

Does weight change modify the association between the consumption of sugar-sweetened beverages and 100% fruit juice and the risk of metabolic syndrome?

Clin Nutr 2021 Aug 28;40(10):5261-5268. Epub 2021 Aug 28.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.1016/j.clnu.2021.08.017DOI Listing
August 2021

Dietary acid load and risk of cardiovascular disease: a prospective population-based study.

BMC Cardiovasc Disord 2021 Sep 11;21(1):432. Epub 2021 Sep 11.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background And Aim: Considering the inconsistencies in the cardiovascular effects of dietary acid load and the impact of dietary acidity on the acid-base homeostasis within the body, we aimed to assess the association of dietary acid load and the risk of cardiovascular disease (CVD) in a prospective community-based study.

Materials And Methods: Participants (n = 2369) free of CVD at baseline (2006-2008) were included from the Tehran Lipid and Glucose Study (TLGS) and followed up for a mean of 6.7 ± 1.4 years. Dietary intakes of the participants were assessed using a semi-quantitative food frequency questionnaire (FFQ). The dietary acid load was evaluated by Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) scores. Both scores have used the macronutrient and micronutrient data of the Food Frequency Questionnaires. Multivariate Cox proportional hazard regression models were used to estimate the 6-years incident risk of CVDs across tertiles of PRAL and NEAP scores.

Results: Mean age and body mass index of participants were 38.5 ± 13.3 years and 26.6 ± 4.8 kg/m at baseline. Within 6.7 ± 1.4 years of follow-up, 79 cases of cardiovascular events were reported. NEAP was significantly associated with the incidence of CVDs (HRs = 0.50, CI 0.32-0.96; P for trend = 0.032); however, after adjusting for potential confounders, no significant associations were observed between PRAL and NEAP scores and the risk of CVDs.

Conclusions: This study failed to obtain independent associations between dietary acid load and the incidence of CVDs among an Asian population.
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http://dx.doi.org/10.1186/s12872-021-02243-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436514PMC
September 2021

Risk of hypertension in school-aged children undergoing a long-term community-based lifestyle intervention: Tehran Lipid and Glucose Study.

Prev Med 2021 Sep 8;153:106799. Epub 2021 Sep 8.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Childhood hypertension which increases the risk of cardiovascular diseases in adulthood is becoming more prevalent. For the first time in the Middle-East region, this study aimed to assess the long-term effectiveness of a community-based lifestyle intervention on the incidence of hypertension in school-aged children during 16 years of follow-up. This study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS). Participants were 2080 children aged 8-18 years with normal blood pressure who were under the coverage of three health care centers selected using multistage cluster random sampling method. One of the health care centers far from the other two was selected for implementing lifestyle intervention (1053 children, 48.2% boys). Triennial examinations were conducted, and survival Cox models were used to assess intervention effects on the incidence of hypertension in boys and girls. Crude incidence rates (per 1000 person-years) of hypertension were 8.11, 3.7, and 5.8 among boys, girls, and the total sample, respectively. Our results showed that HTN has occurred significantly less (P = 0.025) in the intervention group than in the control group, only in female participants. These results remained significant even after adjusting for individuals' and parental characteristics (P = 0.033). Although the risk of hypertension in boys was more than twice that observed in girls, the effectiveness of the recent community-based healthy lifestyle intervention was observed only in girls and not in boys. Further studies are needed to understand gender differences in promoting the effectiveness of similar future programs. The TLGS is registered at Iran Registry for Clinical Trials, a WHO primary registry (http://irct.ir; IRCTID: IRCT138705301058N1).
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http://dx.doi.org/10.1016/j.ypmed.2021.106799DOI Listing
September 2021

A Qualitative Exploration of Body Image from the Perspective of Adolescents with a Focus on Psychological Aspects: Findings from Iran.

Child Psychiatry Hum Dev 2021 Sep 9. Epub 2021 Sep 9.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box 19395-4763, Tehran, Iran.

The current study employs a qualitative approach to uncover the perceptions of Iranian adolescents regarding their bodies, with a focus on the psychological components that contribute to their body image perceptions. Data collection conducted using 13 semi-structured focus group discussions with 42 girls and 42 boys (15-18 years). All focus group discussions were audio recorded and transcribed verbatim. Data analysis was done manually using constant comparative analysis according to the Strauss and Corbin analysis method. Based on the participants' statements, four main themes and related categories emerged from data: (1) Beliefs including uncontrollable body, biased opinion of those around, priority of health, spiritual/religious beliefs and affecting future success, (2) Body-evaluation including direct body evaluation and indirect body evaluation, (3) Feelings and emotions including disgust and hatred, frustration, sadness, shame, envy, fear, approval and satisfaction and (4) Behaviors including lifestyle modifications, beautifying and using make up, extreme dieting, physical inactivity, avoidance behaviors, passive behaviors, aggressive behaviors and social isolation. Findings of the current study provide further information regarding cognitive, emotional and behavioral aspects of body image from the perspectives of adolescents in a West-Asian region.
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http://dx.doi.org/10.1007/s10578-021-01235-1DOI Listing
September 2021

Effects of isolated maternal hypothyroxinemia on adverse pregnancy outcomes.

Arch Gynecol Obstet 2021 Sep 5. Epub 2021 Sep 5.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Purpose: There are conflicting results about the effects of maternal hypothyroidism (IMH) on adverse pregnancy outcomes. This study aimed to investigate the relationship between IMH identified in the first trimester of gestation and adverse pregnancy outcomes.

Methods: In this prospective cohort study, we used data from the Tehran Thyroid and Pregnancy study (TTPs). To diagnose IMH, we considered a threshold of 2.04 for FTI, which was based on the 10th percentile of this marker identified in the 1st trimesters. A generalized linear regression (GLM) model adjusted for the gravidity, urine iodine, and TPOAb status was applied to assess the effects of IMH on adverse pregnancy outcomes, compared to the controls group.

Results: Penalized logistic regression analysis indicated that the adjusted odds ratio (aOR) of Preterm premature rupture of the membranes (PPROM) in women with IMH was 5.43-folder higher than euthyroid group [aOR 5.43, 95% CI (1.40, 21.1), p = 0.01]. Besides, the adjusted odds ratio of low birth weight (LBW) in the IMH group was 2.53-folder higher than the healthy group [aOR 2.53, 95% CI (1.01, 6.33), p = 0.047]. Furthermore, the results of the GLM adjusted model revealed that the mean of neonatal head circumference and weight in the IMH group was around 0.43 cm (95% CI - 0.80, - 0.07, p = 0.02) and 145.4 g (95% CI - 242.6, - 48.1, p = 0.003) lower than euthyroid group, respectively.

Conclusions: This study demonstrated that women with IMH identified in early pregnancy have a higher odds ratio for developing some adverse pregnancy outcomes, including PPROM and LBW compared to their euthyroid counterparts. Also, the neonatal head circumference and weight in the IMH group were lower than in the euthyroid group.
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http://dx.doi.org/10.1007/s00404-021-06226-0DOI Listing
September 2021

Diverse effect of MC4R risk alleles on obesity-related traits over a lifetime: Evidence from a well-designed cohort study.

Gene 2021 Sep 2;807:145950. Epub 2021 Sep 2.

Cellular, and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

This population-based longitudinal study is the first investigation that assesses the association of common MC4R SNPs with the obesity-related parameters over time and determines the effect of risk alleles during the three adulthood life periods (early, middle, and late) in a large Iranian cohort, a population with a unique genetic make-up that has been understudied and relatively unexplored. We obtained the genotype of 5370 unrelated adults who participated in the ongoing Tehran Cardiometabolic Genetic Study (TCGS) cohort project for the common MC4R SNPs. Linear regression and linear mixed model analyses were performed to examine the effect of MC4R polymorphisms on maximum BMI and other obesity-related factors over time. We recognized that several SNPs associated with the maximum BMI and the increased BMI, waist circumference, and waist-hip ratio across Iranian adults over a lifetime. Interestingly, we found that rs9954571-A has a yet unreported protective role against obesity-related factors, including BMI, waist circumference, waist-hip ratio, and triglyceride level. Additionally, a survey of the impact of the MC4R risk score throughout the adulthood life periods indicated that the MC4R risk score is influenced both the elevated BMI and waist circumference only during the early adulthood period. Our findings can expand our knowledge about the MC4R genetic variant's contributions to adulthood obesity and highlight the importance of evaluating the genetic components affecting obesity over a lifetime, which could be considered for obesity clinical screening and treatment.
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http://dx.doi.org/10.1016/j.gene.2021.145950DOI Listing
September 2021

Reduced sensitivity to thyroid hormone is associated with diabetes and hypertension.

J Clin Endocrinol Metab 2021 Sep 4. Epub 2021 Sep 4.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, I. R. Iran.

Background: 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. We evaluated 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 were measured, and serum concentrations of lipids and lipoproteins, fasting blood glucose (FBG), insulin, free T4 (fT4) and TSH were assayed. Thyroid hormone resistance was calculated by thyroid feedback quantile-based index (TFQI) and Iranian-referenced parametric TFQI (PTFQI) and compared with two other indices of TT4RI and TSHI.

Results: TFQI was significantly associated with high BP metabolic syndrome criterion (OR=1.14, 95% CI: 1.06, 1.23) and DM (OR=1.16, 95% CI: 1.04, 1. 30, p=0.009) in euthyroid subjects after adjusting for age, sex, smoking, physical activity, BMI, and HOMA-IR. 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=0.001) and TT4RI (OR=1.08, 95% CI: 1.01, 1.16, P<0.001) 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.
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http://dx.doi.org/10.1210/clinem/dgab646DOI Listing
September 2021

Using Machine Learning Techniques to Predict Factors Contributing to the Incidence of Metabolic Syndrome in Tehran: Cohort Study.

JMIR Public Health Surveill 2021 Sep 2;7(9):e27304. Epub 2021 Sep 2.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.2196/27304DOI Listing
September 2021

Dynamic prediction models improved the risk classification of type 2 diabetes compared with classical static models.

J Clin Epidemiol 2021 Aug 26. Epub 2021 Aug 26.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objective: Dynamic prediction models use the repeated measurements of predictors to estimate coefficients that link the longitudinal predictors to a static model (i.e. Cox regression). This study aims to develop and validate a dynamic prediction for incident type 2 diabetes (T2DM) as the outcome.

Study Design And Setting: Data from the Tehran lipid and glucose study was used to develop (n=5291 individuals; phases 1 to 3) and validate (n=3147 individuals; phases 3 to 6) the dynamic prediction model among individuals aged≥20 years. We used repeated measurements of fasting plasma glucose (FPG) or waist circumference (WC) in the framework of the joint modeling (JM) of longitudinal and time-to-event analysis.

Results: Compared with the Cox which used just baseline data, JM showed the same discrimination, better calibration, and higher clinical usefulness (i.e. with a net benefit considering both true and false positive decisions); all were shown with repeated measurements of FPG/WC. Additionally, in our study, the dynamic models improve the risk reclassification (net reclassification index 33% for FPG and 24% for WC model).

Conclusion: Dynamic prediction models, compared with the static one could yield significant improvements in the prediction of T2DM. The complexity of the dynamic models could be addressed by using decision support systems.
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http://dx.doi.org/10.1016/j.jclinepi.2021.08.026DOI Listing
August 2021

Predictive value of women's weight trajectories in determining familial cardiovascular disorders: a family-based longitudinal study.

Sci Rep 2021 Aug 27;11(1):17317. Epub 2021 Aug 27.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran.

Considering the dynamic nature of body mass index (BMI) and its importance in determining cardiovascular risks, this study aimed to investigate the life-course trajectory pattern of women's BMI and its association with cardiovascular risk factors. A total of 1356 couples with 2976 children were recruited and followed up for an average period of 20 years. Latent growth curve modeling was applied to determine women's BMI trajectories; logistic regression was used to investigate the associations between trajectory patterns and cardiovascular risk factors, including hypertension (HTN), dyslipidemia, diabetes mellitus (DM), and obesity. Women were classified into three trajectories, including normal, stage 1 obesity, and stage 2 obesity. Compared to women's in the normal trajectory group, those in obesity trajectories had higher odds ratios for HTN, DM, and dyslipidemia. Men with obese spouses showed a higher rate of HTN 1.54 (95% CI 1.05-2.25) and DM 1.55; (95% CI 1.00-2.44). The odds of men's obesity were higher in obese spouses (OR 1.70; 95% CI 1.10-2.62). Offspring of stage 2 obese (OR 2.39; 95% CI 1.67-3.44) and stage 1 obese (OR 4.81; 95% CI 3.16-7.34) mothers were more likely to be obese. Our findings emphasized paying more attention to women with excessive weight to promote familial cardiovascular health in the communities.
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http://dx.doi.org/10.1038/s41598-021-96154-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397790PMC
August 2021

Parental Transmission Plays the Major Role in High Aggregation of Type 2 Diabetes in Iranian Families: Tehran Lipid and Glucose Study.

Can J Diabetes 2021 Jun 1. Epub 2021 Jun 1.

Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Background: This study is the first to evaluate familial aggregation, heritability and inheritance mode of type 2 diabetes (T2D) in Tehran Lipid Glucose Study (TLGS) participants as a representative sample of the Iranian population.

Methods: From the ongoing family-based TLGS cohort, 13,741 individuals at least 20 years of age (mean ± standard deviation, 39.71±16.56) were assessed. After correcting family structures using genomic information from the Tehran Cardiometabolic Genetic Study, 2,594 constituent pedigrees were constructed. Familial aggregation was assessed based on genealogic index testing, familial intraclass correlation and positive family history. Family-based heritability was checked with 2 linear mixed models, including 2 different random components: the kinship matrix and the genomic relationship matrix. The mode of inheritance of T2D was investigated by complex segregation analysis (CSA).

Results: Familial aggregation of T2D was significant (p<0.05), and family-based heritability showed a high degree of genetic variation in T2D between individuals at 65% (standard error, 0.034). Within first-degree relatives (parent/offspring and siblings), the likelihood of a parental affect was higher than in siblings (odds ratio, 4.11 vs 1.65). Family history of T2D among first-degree relatives was more noteworthy than for second-degree relatives (odds ratio, 3.84 vs 0.59). CSA revealed that the polygenic model is best to illustrate the mode of inheritance of T2D for TLGS participants.

Conclusions: Our findings demonstrate that the heritability of T2D with polygenic mode in the Iranian population is higher than the global average. We also found that T2D is transmitted equally into siblings, with parental affect the leading risk factor. These data suggest that policymakers should change individual-level to family-level prevention.
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http://dx.doi.org/10.1016/j.jcjd.2021.05.009DOI Listing
June 2021

Risk of hypertension in school-aged children with different parental risk: a longitudinal study from childhood to young adulthood.

BMC Pediatr 2021 08 17;21(1):352. Epub 2021 Aug 17.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O.Box: 19395-4763, Tehran, Islamic Republic of Iran.

Background: Although previous studies have shown the relationship between different parental factors and children's blood pressure status, there is limited data on the cumulative effect of these factors. Considering parental socio-demographic, behavioral and cardio-metabolic characteristics, the current study aimed to distinguish parental risk clusters and their impact on the incidence of hypertension in school-age children over 13 years.

Methods: Parental characteristics of 1669 children, including age, education, employment, smoking, physical activity, metabolic syndrome (MetS), hypertension (HTN), weight status, and diabetes were considered to categorize parents into low and high-risk clusters. Crude incidence rates (per 10,000 person-years) of HTN in children were assessed in each maternal and paternal cluster. Using Cox proportional hazard model, results on the association between parental risk clusters and HTN incidence in children were reported in five different models.

Results: Mean age of children was 13.96 ± 2.89 years, and 51.2% (n = 854) were girls. MetS, HTN, and weight status were the most important factors distinguishing low and high-risk parental clusters, respectively. Crude incidence rates (per 10,000 person-years) of HTN were 86 (95% CI: 71-106) and 38 (95% CI, 29-52) in boys and girls, respectively. Moreover, incidence rates (per 10,000 person-years) of HTN were 50 (95% CI, 40-63) and 80 (95% CI, 64-102) in maternal low and high-risk clusters, respectively. The incidence rates (per 10,000 person-years) of HTN in paternal low and high-risk clusters were 53 (95% CI, 41-70) and 68 (95% CI, 56-84), respectively.

Conclusion: Our findings underscore the prognostic value of maternal characteristics in predicting the incidence of HTN in their offspring. The current results could be valuable in planning related programs to prevent hypertension in similar communities.
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http://dx.doi.org/10.1186/s12887-021-02807-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369749PMC
August 2021

Incidence and risk factors of severe non-proliferative/proliferative diabetic retinopathy: More than a decade follow up in the Tehran Lipids and Glucose Study.

J Diabetes Investig 2021 Aug 17. Epub 2021 Aug 17.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aims/introduction: To examine the incidence rate of severe non-proliferative and proliferative diabetic retinopathy (severe-NPDR/PDR) and determine its potential risk factors.

Materials And Methods: The study consisted of 1,169 participants (675 women) with type 2 diabetes mellitus, aged ≥20 years. A trained interviewer collected information about the history of pan-retinal photocoagulation as a result of diabetic retinopathy. Multivariable Cox proportional hazards regression models were applied.

Results: We found 187 cases (126 women) of severe-NPDR/PDR during a median follow-up period of 12.7 years; the corresponding incidence rate was 13.6 per 1,000 person-years. Being overweight (hazard ratio [HR], 95% confidence interval [CI] 0.60, 0.39-0.92) and obese (HR 0.48, 95% CI 0.27-0.83) were associated with lower risk, whereas being smoker (HR 1.75, 95% CI 1.12-2.74), having fasting plasma glucose levels 7.22-10.0 mmol/L (HR 2.81, 95% CI 1.70-4.62), fasting plasma glucose ≥10 mmol/L (HR 5.87, 95% CI 3.67-9.41), taking glucose-lowering medications (HR 2.58, 95% CI 1.87-3.56), prehypertension status (HR 1.65, 95% CI 1.05-2.58) and newly diagnosed hypertension (HR 1.96, 95% CI 1.06-3.65) increased the risk of severe-NPDR/PDR. Among newly diagnosed diabetes patients, being male was associated with a 59% lower risk of severe-NPDR/PDR (HR 0.41, 95% CI 0.21-0.79). Furthermore, patients who had an intermediate level of education (6-12 years) had a higher risk of developing PDR (HR 1.86, 95% CI 1.05-3.30) compared with those who had <6 years of education.

Conclusions: Among Iranians with type 2 diabetes mellitus, 1.36% developed severe-NPDR/PDR annually. Normal bodyweight, being a smoker, out of target fasting plasma glucose level, prehypertension and newly diagnosed hypertension status were independent risk factors of severe-NPDR/PDR. Regarding the sight-threatening entity of advanced diabetic retinopathy, the multicomponent strategy to control diabetes, abstinence of smoking and tight control of blood pressure should be considered.
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http://dx.doi.org/10.1111/jdi.13647DOI Listing
August 2021

Predisposing factors of long-term responsiveness in a cardio-metabolic cohort: Tehran Lipid and Glucose Study.

BMC Med Res Methodol 2021 08 9;21(1):161. Epub 2021 Aug 9.

Endocrine Research Center, Research Institute for Endocrine Sciences, ShahidBeheshti University of Medical Sciences, Tehran, Iran.

Background: Non-participation in cohort studies, if associated with both the exposure and occurrence of the event, can introduce bias in the estimates of interest. This study aims to identify factors associated with follow-up participation in Tehran Lipid and Glucose Study, a large-scale community-based prospective study in West Asia.

Methods: A sample of 10,368 adults from TLGS was included in the analysis. All analyses were split according to sex and age groups (20-39, 40-59, and 60 years). The associations between socio-demographic, health, and lifestyle factors with response rate were identified using the Generalized Estimating Equations model.

Results: Over the median of 15.7 years of follow up the response rate was 64.5%. The highest response rate was observed in those aged 40-59 years for both sexes. Current smokers had lower odds of response in both sexes for all age groups, ranging from 0.51 to 0.74, p < 0.01. In young adults, being single (OR = 0.79, OR = 0.57, p ≤ 0.01, respectively for men and women) and unemployed (OR = 0.73, OR = 0.76, p ≤ 0.01, respectively for men and women) in both sexes, high physical activity in men (OR = 0.77, p < 0.01), high education (OR = 0.75, p = 0.02) and obesity (OR = 0.85, p = 0.05) in women were associated with lower response rate. For the middle-aged group, diabetes in men (OR = 0.77, p = 0.05) and hypertension (OR = 0.84, p = 0.05), and having a history of cancer (OR = 0.43, p = 0.03) in women were factors associated with lower response rates. Finally, interventions for both sexes (OR = 0.75, OR = 0.77, p ≤ 0.05, respectively for men and women) and being divorced/widow in women (OR = 0.77, p = 0.05) were the factors associated with the lower response rate in the elderly.

Conclusions: Long-term participation was influenced by socio-demographic, health, and lifestyle factors in different sex- and age-specific patterns in TLGS. Recruitment strategies targeting these factors may improve participant follow-up in longitudinal studies.
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http://dx.doi.org/10.1186/s12874-021-01351-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353800PMC
August 2021

Endogenous estrogen exposure and chronic kidney disease; a 15-year prospective cohort study.

BMC Endocr Disord 2021 Aug 4;21(1):155. Epub 2021 Aug 4.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Despite strong evidence demonstrating the role of estrogen as a protective factor for kidney function in women, limited data are available regarding the influence of endogenous estrogen exposure (EEE) on chronic kidney disease (CKD). The present study aimed to assess the incidence of CKD in women with various levels of EEE.

Methods: In a prospective population-based study over a 15-year follow-up, a total of 3043 eligible women aged 30-70 years, participating in Tehran-Lipid and Glucose-Study were recruited and divided into two groups (EEE < 11 and EEE ≥ 11 years). EEE calculated based on age at menarche, age at menopause, number and duration of pregnancies, lactation, and duration of oral contraceptive use after excluding the progesterone dominant phase of the menstrual cycle. Cox's proportional hazards model was applied to estimate the hazard ratio of CKD between the study groups, after adjusting for confounders.

Results: The total cumulative incidence rate of CKD was 50.1 per 1000 person years; 95% CI: 47.7-52.6); this was 53.9 (95%CI, 50.2-57.8) and 47.1 (95%CI, 44.0-50.4) per 1000 person years in women with EEE < 11 and EEE ≥ 11 years, respectively. The model adjusted for age, BMI, smoking, hypertension, and diabetes showed that the hazard ratio (HR) of incidence CKD in women with EEE < 11 compare to those with EEE ≥ 11 years in the subgroup of women aged< 45 years was 2.66(95% CI, 2.2, 3.2), whereas, in the subgroup aged ≥45 years, it was 1.22 (95% CI, 1.04, 1.4).

Conclusion: This study shows a higher HR of CKD incidence in women with low EEE levels in their later life. Screening of these women for CKD may be recommended.
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http://dx.doi.org/10.1186/s12902-021-00817-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336110PMC
August 2021

Sudden cardiac death among Iranian population: a two decades follow-up of Tehran lipid and glucose study.

Sci Rep 2021 Aug 3;11(1):15720. Epub 2021 Aug 3.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box, 19395-4763, Tehran, Iran.

Sudden cardiac death (SCD) is described as death within one hour, if observed, from the onset of symptoms, and within 24 h of being alive and well if not observe. Study population includes 3705 men and 4446 women, aged ≥ 30 years. Multivariable Cox proportional hazard models were used to determine the risk factors associated with SCD. After a median follow-up of 17.9 years, 244 SCD (165 in males) occurred. The age-standardized incidence rate (95% confidence intervals (CI)) of SCD was 2.3 (2.1-2.7) per 1000 person-year. Current smoking [Hazard ratio (HR): 2.43, 95% CI: 1.73-3.42], high waist circumference [1.49: 1.04-2.12], hypertension [1.39: 1.05-1.84], type 2 diabetes mellitus [2.78: 2.09-3.69], pulse rate ≥ 90 beats per/minute [1.72: 1.22-2.42] and prevalent cardiovascular disease [1.75: 1.26-2.45] were significant risk factors. The corresponding population attributed fractions (PAF) were 14.30, 16.58, 14.03, 19.60, 7.62, and 8.30, respectively. Being overweight [0.58: 0.40-0.83] and obese [0.61: 0.38-0.98] decreased the risk of SCD. After excluding known diabetes cases from our data analysis, the newly diagnosed diabetes still showed an HR of 2.0 (1.32-3.00) with a PAF of 7.15% in the full adjustment model. To deal with sudden death as a catastrophic outcome, multi-component strategies by policy health makers are suggested.
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http://dx.doi.org/10.1038/s41598-021-95210-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333266PMC
August 2021

Time-varying association between physical activity and risk of diabetes in the early and late adulthood: A longitudinal study in a West-Asian country.

Prim Care Diabetes 2021 Jul 26. Epub 2021 Jul 26.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: The time-varying association between physical activity (PA) and incidence of type 2 diabetes (T2DM) is still unclear. The present study aimed to investigate this association in the early- and late-adulthood during a 9-year follow-up.

Methods: This study was conducted on 3905 participants in early and late adulthood, using the Tehran Lipid and Glucose Study (TLGS) dataset. PA was assessed via the Iranian version of Modified Activity Questionnaire (MAQ). The association between trend of PA and incident T2DM was investigated using time-varying Cox's proportional hazard model. Variables including job, education, smoking and body mass index (BMI) were adjusted in the final model.

Results: The distribution of sex- and age-specific levels of PA changed significantly over time. Compared with physically inactive women, for older women with high level of PA, the risk of T2DM was 0.64 (95% CI: 0.43-0.95, P = 0.02) in adjusted model. Moreover, hazard for low PA group was significantly higher than the moderate group, and for these two groups were significantly higher than high PA level (P < 0.05).

Conclusion: High PA level can postpone the incident T2DM in early-aged and elderly women, over time. Therefore, gender and age are of great importance in designing the PA modifying programs to prevent T2DM.
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http://dx.doi.org/10.1016/j.pcd.2021.07.012DOI Listing
July 2021

Anthropometric indices and the risk of incident sudden cardiac death among adults with and without diabetes: over 15 years of follow-up in The Tehran Lipid and Glucose Study.

Diabetol Metab Syndr 2021 Jul 28;13(1):82. Epub 2021 Jul 28.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Parvaneh Street, Velenjak, P.O. Box no19395-4763, Tehran, Iran.

Background: We investigated the association of anthropometric indices including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and hip circumference (HC) with the risk of incident sudden cardiac death (SCD) among Iranian population with and without type 2 diabetes mellitus (T2DM).

Methods: The study population included 9,089 subjects without and 1,185 subjects with T2DM, aged ≥ 20 years. Participants were recruited in 1999-2001 or 2001-2005, and followed for incident SCD annually, up to 20 March 2018. Multivariate Cox proportional hazard models, adjusted for traditional risk factors of cardiovascular disease, were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of anthropometric indices (as continuous and categorical variables).

Results: During a follow-up of over 15 years, 144 (1.58%) and 86 (7.26%) incident SCD occurred in non-T2DM and T2DM groups, respectively. Among non-T2DM group, a 1 standard deviation (SD) increase in WHtR was associated with higher risk of incident SCD by a HR of 1.23 (95% CI: 1.00-1.50) in the multivariable model. From the first quartile to the fourth quartile of WHtR, the trend of SCD risk was significant in age- and sex-adjusted analysis (P-value for trend: 0.041). Other indices did not show significant associations with SCD. Among T2DM group, a 1 SD increase in WHR had a HR of 1.36 (1.05-1.76) in the multivariable model. Considering WHR as categorical variables, the trend of SCD risk across quartiles of WHR was significant. Furthermore, a 1 SD increase in HC led to reduced risk of incident SCD with a HR of 0.75 (0.58-0.97) in multivariable analysis; this lower risk remained significant even after adjustment for WC. Compared to the first quartile, the fourth quartile of HC also showed a HR of 0.50 (0.25-0.99) (P-value for trend = 0.018). BMI, WC, and WHtR did not have significant associations with incident SCD.

Conclusion: In our long-term population-based study, we demonstrated central but not general obesity (as assessed by WHR in participants with T2DM, and WHtR in participants without T2DM) as a herald of incident SCD. Moreover, HC can have an inverse association with SCD among participants with T2DM.
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http://dx.doi.org/10.1186/s13098-021-00701-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320203PMC
July 2021

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

Cytogenet Genome Res 2021 26;161(5):227-235. Epub 2021 Jul 26.

Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Inactivation of tumor suppressor genes, such as RAP1GAP, by hypermethylation of their regulatory region can give rise to thyroid tumors. The aim of this study was to investigate the expression of the RAP1GAP gene and the DNA methylation patterns of its CpG74a, CpG74b, and CpG24 in an Iranian population with differentiated thyroid cancer (DTC). In this study, 160 individuals who underwent thyroidectomy in the Tehran Erfan Hospital between 2018 and 2020 were selected. DNA methylation patterns of selected CpG islands (CpG74a, CpG74b, and CpG24) were determined using methylation-specific PCR. The mRNA expression and protein level of -RAP1GAP were also evaluated. SW1736 and B-CPAP cells were treated with 5-aza-2'-deoxycytidine (5-Aza) to demethylate these regions. The hypermethylation rates of CpG74a and CpG24 in DTC samples were significantly higher than in the control. The mRNA expression and protein level of -RAP1GAP were significantly decreased in the DTC group. In the DTC group, hypermethylation in CpG74a was correlated with decreasing RAP1GAP expression (R2: 0.34; p = 0.043). CpG74a with a specificity of 86.4% has significant prediction power to distinguish between DTC and normal thyroid tissues. Additionally, hypermethylation of CpG74a was significantly associated with higher tumor stages (stage III-IV: 77%; stage I-II: 23%; p = 0.012). Increasing expression of RAP1GAP after demethylation with 15 µM of 5-Aza was observed in both cell lines. These results indicate that DNA hypermethylation in CpG74a can be considered as an epigenetic biomarker in DTC.
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http://dx.doi.org/10.1159/000516122DOI Listing
September 2021

Socioeconomic status and lifestyle factors modifies the association between snack foods intake and incidence of metabolic syndrome.

Nutr J 2021 07 22;20(1):70. Epub 2021 Jul 22.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.1186/s12937-021-00728-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299611PMC
July 2021

Trajectories of cardiovascular disease risk and their association with the incidence of cardiovascular events over 18 years of follow-up: The Tehran Lipid and Glucose study.

J Transl Med 2021 07 16;19(1):309. Epub 2021 Jul 16.

Department of Epidemiology and Biostatistics, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Understanding long-term patterns (trajectories) of cardiovascular diseases (CVD) risk and identifying different sub-groups with the same underlying risk patterns could help facilitate targeted cardiovascular prevention programs.

Methods: A total of 3699 participants of the Tehran Lipid and Glucose Study (TLGS) (43% men, mean age = 53.2 years), free of CVD at baseline in 1999-2001 and attending at least one re-examination cycle between the second (2002-2005) and fourth cycles (2009-2011) were included. We examined trajectories of CVD risk, based on the ACC/AHA pooled cohort equation, over ten years and subsequent risks of incident CVD during eight years later. We estimated trajectories of CVD risk using group-based trajectory modeling. The prospective association of identified trajectories with CVD was examined using Cox proportional hazard model.

Results: Three distinct trajectories were identified (low-low, medium-medium, and high-high risk). The high-high and medium-medium CVD risk trajectories had an increasing trend of risk during the time; still, this rising trend was disappeared after removing the effect of increasing age. Upon a median 8.4 years follow-up, 146 CVD events occurred. After adjusting for age, the medium-medium and high-high trajectories had a 2.4-fold (95% CI 1.46-3.97) and 3.46-fold (95% CI 1.56-7.70) risk of CVD compared with the low-low group, respectively. In all trajectory groups, unfavorable increasing in fasting glucose, but favorable raising in HDL and decreasing smoking and total cholesterol happened over time.

Conclusions: Although the risk trajectories were stable during the time, different risk factors varied differently in each trajectory. These findings emphasize the importance of attention to each risk factor separately and implementing preventive strategies that optimize CVD risk factors besides the CVD risk.
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http://dx.doi.org/10.1186/s12967-021-02984-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284005PMC
July 2021

Weight change and risk of cardiovascular disease among adults with type 2 diabetes: more than 14 years of follow-up in the Tehran Lipid and Glucose Study.

Cardiovasc Diabetol 2021 07 12;20(1):141. Epub 2021 Jul 12.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Parvaneh Street, Velenjak, P.O. Box: 19395-4763, Tehran, Iran.

Background: To examine the impact of weight change on incident cardiovascular disease and coronary heart disease (CVD/CHD) among an Iranian population with type 2 diabetes mellitus (T2DM).

Methods: The study population included 763 participants with T2DM aged ≥ 30 years without a history of CVD and cancer at baseline. Two weight measurements done at baseline and about 3 years later. Based on their weight change, they categorized into: > 5% loss, 3-5% loss, stable (± < 3%), 3-5% gain, > 5% gain. Participants were then followed for incident CVD/CHD annually up to 20 March 2018. Multivariable Cox proportional hazard models, adjusted for age, sex, body mass index, educational level, current smoking, glucose-lowering drug use, family history of CVD, hypertension, hypercholesterolemia, chronic kidney disease, and fasting plasma glucose (FPG) were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of weight change categories for incident CVD/CHD, considering stable weight as reference.

Results: After the weight change measurement, during a median follow-up of 14.4 years, 258 CVD and 214 CHD occurred. Over 5% weight gain was associated with reduced risks of CVD and CHD development by the HRs of 0.70 [95% CI 0.48-1.01; P-value: 0.058] and 0.61 [0.40-0.93], respectively, in multivariable analysis. After further adjustment for FPG change, the HRs of weight gain > 5% were attenuated to 0.75 [0.51-1.10; P-value: 0.138] and 0.66 [043-1.01; P-value: 0.053] for incident CVD and CHD, respectively. The effect of weight loss > 5% was in opposite direction among those older versus younger than 60 years; with suggestive increased risk (not statistically significant) of incident CHD/CVD for the older group. Moreover, weight gain > 5% significantly reduced the risk of CHD only among those older than 60 years (P-value for interaction < 0.2). Furthermore, weight gain > 5% had an association with lower risk of CVD and CHD among sulfonylurea users (0.56 [0.32-0.98] for CVD and 0.54 [0.29-0.99] for CHD).

Conclusions: Our results with a long-term follow-up showed that weight gain > 5% was associated with better CVD/CHD outcomes among Iranian participants with T2DM, especially older ones. Moreover, we did not find an unfavorable impact on incident CVD/CHD for sulfonylurea-induced weight gain.
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http://dx.doi.org/10.1186/s12933-021-01326-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276460PMC
July 2021

Long-term glucose variability and incident cardiovascular diseases and all-cause mortality events in subjects with and without diabetes: Tehran Lipid and Glucose Study.

Diabetes Res Clin Pract 2021 Aug 8;178:108942. Epub 2021 Jul 8.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Aim: To examine whether visit to visit variability (VVV) of fasting plasma glucose (FPG) is associated with incident cardiovascular diseases (CVD) and all-cause mortality in individuals with and without type 2 diabetes (T2D).

Methods: A total of 4756 participants aged ≥30 years entered the study in 2002-2005 and underwent two subsequent examinations in 2005-2008 and 2008-2011. FPG variability measures included standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of mean (VIM). Multivariate Cox proportional hazard models were used to assess the risk of incident CVD and all-cause mortality for each unit increase in different FPG variability measures.

Results: During a median follow-up of 18.14 years after baseline recruitment, 492 incident cardiovascular diseases and 338 all-cause mortality were recorded. Among individuals without T2D, the multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD were 1.02 (1.01-1.04), 1.02 (1.01-1.04), 1.01 (1.00-1.02), and 1.01 (1.00-1.01) for SD, CV, ARV, and VIM, respectively (all P-values <0.05). Among individuals with T2D, the corresponding HRs and 95% CIs for all-cause mortality were 1.01 (1.00-1.02), 1.02 (1.01-1.03), 1.01 (1.00-1.02), and 1.01 (1.00-1.01), respectively (all P-values <0.05).

Conclusion: Long-term (VVV) of FPG is significantly associated with increased risk of CVD among participants without T2D, and all-cause mortality among participants with T2D.
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http://dx.doi.org/10.1016/j.diabres.2021.108942DOI Listing
August 2021

Dairy-originated digestion-resistant and bioactive peptides increase the risk of hypertension: Tehran Lipid and Glucose Study.

Hypertens Res 2021 Sep 5;44(9):1194-1204. Epub 2021 Jul 5.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Milk-protein-derived bioactive peptides (BPs) have been proposed as modulators of different regulatory processes involved in blood pressure regulation. Studies on the long-term effects of BPs on blood pressure have not yet been conducted. We aimed to investigate the association of dairy-originated BPs with the risk of hypertension (HTN) in the Tehran Lipid and Glucose Cohort Study (TLGS). In this cohort study, 4378 subjects with a mean follow-up period of 3.1 years were included in the final analysis. Dietary intake, physical activity, demographic, and anthropometric data and blood pressure measurements were obtained for all participants. Various types of dairy-originated BPs were determined by an in silico method. High intake of total digestion-resistant and bioactive peptides (OR: 1.31, CI 95%: 1.01-1.70), dipeptides (OR: 1.33, CI 95%: 1.03-1.73), peptides with more than seven residues (OR: 1.32, CI 95%: 1.01-1.71), glycosylated residues (OR: 1.39, CI 95%: 1.07-1.80), highly hydrophilic peptides (OR: 1.32, CI 95%: 1.01-1.71), and low hydrophobic peptides (OR: 1.32, CI 95%: 1.01-1.71) was associated with an increased risk of HTN in the adjusted model. In addition, subjects in the higher tertile of anti-HTN peptide (OR: 1.33, CI 95%: 1.02-1.72) and antidiabetic peptide (OR: 1.35, CI 95%: 1.04-1.76) intake had a higher risk of HTN than those in the lower tertile. No significant association emerged between calcium intake from dairy and incident risk of HTN. Our results showed that the intake of some forms of digestion-resistant and BPs, such as anti-HTN peptides, dipeptides, and peptides with more than seven residues, can increase the risk of HTN in the TLGS population.
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http://dx.doi.org/10.1038/s41440-021-00692-4DOI Listing
September 2021

Risk of chronic kidney disease in women with a history of preterm delivery: Tehran Lipid and Glucose Study.

J Nephrol 2021 Jul 3. Epub 2021 Jul 3.

Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Preterm delivery (PTD) may predict the risk of long-term maternal complications. Little is known about the association between preterm delivery and maternal risk of chronic kidney disease (CKD).This study aimed to explore whether a history of preterm delivery is associated with the risk of maternal CKD.

Methods: In this population-based cohort study within the framework of the Tehran Lipid and Glucose Study (TLGS), a total of 3035 women with at least one delivery met our eligibility criteria. A time-dependent Cox proportional-hazards regression model was used to measure the hazard ratios (HRs) and 95% confidence intervals (CIs) for evaluating the association between history of preterm delivery and risk of CKD, adjusted for smoking, parity, age at first delivery, body mass index, educational level, preeclampsia, and gestational diabetes mellitus.

Results: A total of 212 women with a history of at least one preterm delivery and 2823 women with term delivery were included. The median (interquartile range) follow-up in the preterm and term delivery groups was 16 (13.0-17.0) and 16 (14.0-17.0) years, respectively. The results of multivariate Cox regression model, adjusted for confounders, showed that the risk of CKD significantly increased by 46% in women with a history of preterm delivery. Moreover, according to the time-dependent Cox regression analysis, the risk of CKD in women with a history of preterm delivery was 2.68 (95% CI 1.02, 7.05, P = 0.04) fold higher than among those with no history of  preterm delivery.

Conclusion: Pregnancy if complicated by preterm delivery, may increase the risk of future maternal morbidities. Our findings suggest that a history of preterm delivery was associated with an increased maternal risk of CKD in the long term. Further longitudinal studies are needed to confirm our findings.
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http://dx.doi.org/10.1007/s40620-021-01103-0DOI Listing
July 2021

Dietary and lifestyle inflammatory scores and risk of incident diabetes: a prospective cohort among participants of Tehran lipid and glucose study.

BMC Public Health 2021 07 2;21(1):1293. Epub 2021 Jul 2.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Inflammation is a precursor of chronic disease, which is affected by lifestyle and dietary habits. Recently empirical dietary inflammatory patterns (EDIP), dietary inflammation scores (DIS), and lifestyle inflammation scores (LIS) were developed to indicate lifestyle and dietary contributions in systemic inflammation. The current study aimed to investigate the associations between these indices and the incidence of diabetes among Tehranian adults.

Methods: A total of 4624 individuals, aged 20-75 years, who were free of diabetes at baseline (2008-2011), were followed for 5.71 years (2014-2017) to ascertain incident diabetes. Dietary intakes were collected at baseline using the food frequency questionnaire. The hazard ratio (HR) of diabetes was calculated by Cox proportional hazards regression across quartiles of EDIP, DIS, and LIS, adjusted for potential confounders.

Results: The mean ± SD for the age and BMI of the study population (45.1% male) were 40.8 ± 12.7 years and 27.1 ± 4.1 Kg.m2, respectively. At the end of the follow-up, 329 (7.1%) diabetes cases were identified. In the multivariable-adjusted model, individuals in the highest compared to the lowest quartile of EDIP (HR = 0.83; 95%CI:0.59-1.15, p for trend = 0.286), and LIS (HR = 2.41; 95%CI:1.61-3.60, P for trend < 0.001) had increased risk of diabetes. However, no significant associations were found between the score of DIS and diabetes incidents (HR = 0.83; 95%CI:0.59-1.15, p for trend = 0.286).

Conclusion: Greater adherence to EDIP and LIS scores was associated with a higher risk of diabetes, while no significant association was found between the DIS score and diabetes incident.
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http://dx.doi.org/10.1186/s12889-021-11327-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254228PMC
July 2021

Long term prognostic implication of newly detected abnormal glucose tolerance among patients with stable cardiovascular disease: a population-based cohort study.

J Transl Med 2021 06 30;19(1):277. Epub 2021 Jun 30.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Yamen Street, Velenjak, P.O. Box: 19395-4763, Tehran, Iran.

Background: Fasting plasma glucose (FPG) and 2-h post challenge plasma glucose (2 h-PCPG), whether as continuous or categorical variables, are associated with incident cardiovascular disease (CVD) and diabetes; however, their role among patients with existing CVD is a matter of debate. We aimed to evaluate associations of different glucose intolerance states with recurrent CVD and incident diabetes among subjects with previous CVD.

Methods: From a prospective population-based cohort, 408 Iranians aged  ≥  30 years, with history of CVD and without known diabetes were included. Associations of impaired fasting glucose (IFG) according to the American Diabetes Association (ADA) and World Health Organization (WHO) criteria, impaired glucose tolerance (IGT), newly diagnosed diabetes (NDM) with outcomes of interest were determined by multivariable Cox proportional hazard models after adjustment for traditional risk factors. Furthermore, FPG and 2 h-PCPG were entered as continuous variables.

Results: Over a decade of follow-up, 220 CVD events including 89 hard events (death, myocardial infarction and stroke) occurred. Regarding prediabetes, only IFG-ADA was associated with increased risk of hard CVD [hazard ratio(HR), 95%CI: 1.62,1.03-2.57] in the age-sex adjusted model. In patients with NDM, those with FPG ≥ 7 mmol/L were at higher risk of incident CVD/coronary heart disease(CHD) and their related hard outcomes (HR ranged from 1.89 to 2.84, all P < 0.05). Moreover, those with 2 h-PCPG ≥ 11.1 mmol/L had significant higher risk of CVD (1.46,1.02-2.11), CHD (1.46,1.00-2.15) and hard CHD (1.95:0.99-3.85, P = 0.05). In the fully adjusted model, each 1 SD increase in FPG was associated with 20, 27, 15 and 25% higher risk of CVD, hard CVD, CHD and hard CHD, respectively; moreover each 1 SD higher 2 h-PCPG was associated with 21% and 16% higher risk of CVD, and CHD, respectively. Among individuals free of diabetes at baseline (n = 361), IFG-ADA, IFG-WHO and IGT were significantly associated with incident diabetes (all P < 0.05); significant associations were also found for FPG and 2 h-PCPG as continuous variables (all HRs for 1-SD increase > 2, P < 0.05).

Conclusions: Among subjects with stable CVD, NDM whether as high FPG or 2 h-PCPG, but not pre-diabetes status was significantly associated with CVD/CHD and related hard outcomes.
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http://dx.doi.org/10.1186/s12967-021-02950-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243871PMC
June 2021

The dynamics of metabolic syndrome development from its isolated components among Iranian adults: findings from 17 years of the Tehran lipid and glucose study (TLGS).

J Diabetes Metab Disord 2021 Jun 1;20(1):95-105. Epub 2021 Feb 1.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Evaluating the process of changes in the Metabolic Syndrome (MetS) components over time is one of the ways to study of the MetS natural history. This study aimed to determine the trend of changes in the progression of MetS from its isolated components.

Methods: This longitudinal study was performed on four follow-up periods of the Tehran Lipid and Glucose Study (TLGS) between 1999 and 2015. The research population consisted of 3905 adults over the age of 18 years. MetS was diagnosed based on the Joint Interim Statement (JIS). The considered components were abdominal obesity, hypertension, hyperglycemia, and dyslipidemia.

Results: The highest incidence of MetS from its components was related to hypertension in the short term (3.6-year intervals). In the long run, however, the highest increase in the MetS incidence occurred due to abdominal obesity. Overall, the incidence of MetS increased due to obesity and dyslipidemia, but decreased due to the other factors. Nonetheless, the trend of MetS incidence from all components increased in total. The most common components were dyslipidemia with a decreasing trend and obesity with an increasing trend during the study.

Conclusion: The results indicated that obesity and hypertension components played a more important role in the further development of MetS compared to other components in the Iranian adult population. This necessitates careful and serious attention in preventive and control planning.
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http://dx.doi.org/10.1007/s40200-020-00717-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212343PMC
June 2021

Association of Dietary Diabetes Risk Reduction Score With Risk of Cardiovascular Diseases in the Iranian Population: Tehran Lipid and Glucose Study.

Heart Lung Circ 2021 Jun 24. Epub 2021 Jun 24.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: There are no data available regarding the association of dietary diabetes risk reduction score (DDRRS) and risk of cardiovascular disease (CVD) worldwide. We aimed to investigate the association of the DDRRS with the risk of CVD outcomes in a prospective population-based study.

Method: Individuals without CVD (n=2,195) were recruited from participants of the Tehran Lipid and Glucose Study (2006-2008) and followed for a mean of 6.7 years. The DDRRS was determined on the basis of eight components using a validated 168-item food frequency questionnaire. Cox proportional hazard regression models, adjusted for potential confounders, were used to estimate the hazard ratios and 95% confidence interval (CI) of CVD across quartiles of DDRRS.

Results: The mean ± standard deviation age of participants (44.8% male) was 38.8±13.0 years at baseline. Median DDRRS for all patients was 23 (intequartile range 20-26). During follow-up, 77 (3.5%) new cases of CVD were identified. After adjustment for confounding variables, including age, sex, body mass index, physical activity, smoking, energy intake, diabetes, and hypertension, no association was found between DDRRS and risk of CVD (odds ratio, 0.70; 95% CI, 0.36-1.37 [p-value for trend=0.351]).

Conclusions: The findings of this study showed that higher DDRRS is not associated with risk of CVD events.
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http://dx.doi.org/10.1016/j.hlc.2021.05.091DOI Listing
June 2021
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