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Abstract Previous epidemiologic studies debated the association of body mass index (BMI) trends with cardiovascular disease and mortality. This study aimed to evaluate the association of BMI variability and slope with the incidence of Type 2 diabetes mellitus (T2DM) in a sex-stratified 15.8-year follow-up in the population-based Tehran Lipid and Glucose Study (TLGS). Of 10,911 individuals aged 20–60 years, 4981 subjects were included and followed for 15.8-years. The slope coefficient of BMI in the linear regression model represented individuals’ BMI trends up to the incidence of DM. The root mean squared error (RMSE) of the BMI linear trend was selected to reflect BMI variability through six follow-ups. Cox proportional hazards regression was used to investigate the association of the baseline BMI, BMI slope and RMSE with the incidence of T2DM among men and women. Multivariable-adjusted HRs of T2DM for each SD increment in BMI slope was 1.18 (95% CI: 0.94–1.48, p = 0.161) in normal weight men and 1.26 (95% CI: 1.10–1.44, p = 0.001) in overweight and obese men. However, in women, each SD increment in BMI slope increased the risk of T2DM with a HR of 1.19 (95% CI: 1.01–1.40, p = 0.039) in normal weight, and 1.14 (95% CI: 1.08–1.19, p

Abstract Background Preventing overweight in childhood and subsequent stages of life is still a global challenge. Despite numerous relevant lifestyle interventions, data on their impact on different BMI change pathways over time is rare. The present study aimed to investigate the effect of a multi-setting lifestyle intervention on BMI trajectories from childhood to young adulthood. Methods A multi-setting lifestyle intervention at the school, family, and community levels have been conducted in the Tehran Lipid and Glucose Study framework. A total of 2145 children (4–18 years, 49% boys, and 18% intervention) were recruited for the baseline assessment and were followed through five follow-up examinations during a median of 16.1 years. Using a group-based trajectory model, BMI trajectories from childhood to young adulthood were identified, and their association with the implemented intervention was assessed. Results Four trajectory groups of BMI from childhood to young adulthood were identified, including Normal weight (41%), Young adulthood overweight (36%), Early childhood increasing overweight and adulthood obesity (19%), and Early childhood increasing obesity (4%). Only Young adulthood overweight and Early childhood increasing obesity were affected by the intervention and were concomitant with lower BMI levels than the control group, with the highest estimated effect in the latter (β=-0.52 and p = 0.018; β=-1.48 and p

Abstract Background C-peptide offers potential as a marker to indicate childhood metabolic outcomes. Measuring C-peptide concentration might have better future utility in the risk stratification of neonates born to overweight or diabetic mothers. Prior research has tried to bring this matter into the light; however, the clinical significance of these associations is still far from reach. Here we sought to investigate the associations between fetomaternal metabolic variables and umbilical cord blood C-peptide concentration. Methods For the present study, 858 pregnant women were randomly selected from among a sub-group of 35,430 Iranian pregnant women who participated in a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. Their umbilical cord (UC) blood C-peptide concentrations were measured, and the pregnancy variables of macrosomia/large for gestational age (LGA) and primary cesarean section (CS) delivery were assessed. The variation of C-peptide concentrations among GDM and macrosomia status was plotted. Due to the skewed distribution of C-peptide concentration in the sample, median regression analysis was used to identify potential factors related to UC C-peptide concentration. Results In the univariate model, positive GDM status was associated with a 0.3 (95% CI: 0.06 − 0.54, p = 0.01) increase in the median coefficient of UC blood C-peptide concentration. Moreover, one unit (kg) increase in the birth weight was associated with a 0.25 (95% CI: 0.03 − 0.47, p = 0.03) increase in the median coefficient of UC blood C-peptide concentration. In the multivariate model, after adjusting for maternal age, maternal BMI, and macrosomia status, the positive status of GDM and macrosomia were significantly associated with an increase in the median coefficient of UC blood C-peptide concentration (Coef.= 0.27, 95% CI: 0.13 − 0.42, p

Abstract Aims/Introduction To evaluate the association between ideal cardiovascular health metrics (ICVHM) and incident type 2 diabetes mellitus among Iranian men and women. Materials and Methods The study population included 7,488 Iranian adults aged ≥20 years (4,236 women) free from diabetes at baseline. The ICVHM was defined according to the American Heart Association's 2020 impact goals. The multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratios (HRs) for ICVHM both as continuous and categorical variables. Results Over the median of 9.1 years of follow‐up, we identified 922 new cases of type 2 diabetes mellitus (526 women). Body mass index

Background: Metabolic syndrome (MetS) is accompanied by chronic low-grade inflammation, and inflammatory markers like high-sensitivity C-reactive protein(hs-CRP), interleukin-6(IL-6), and homocysteine(Hcy) contribute to inflammation, obesity, and insulin resistance. Adiponectin(AdipoQ) and interleukin-10(IL-10) are anti-inflammatory markers that play protective roles in MetS. This study aimed to investigate the association between these biochemical marker changes and MetS in a sample of the Tehranian population during six years of follow-up. Methods: In this longitudinal study, 340 adults at baseline and after a six-year follow-up, aged ≥18 years, were selected randomly from the Tehran Lipid and Glucose Study (TLGS). MetS was defined according to the Joint Interim Statement (JIS) criteria. Individuals were categorized into four groups based on their MetS status at baseline and follow-up: 1) non-MetS: participants who did not have MetS at both baseline and follow-up; 2) incident MetS: participants who did not have MetS at baseline but developed MetS during the follow-up ; 3) recovery MetS: participants who had MetS at baseline but no longer had MetS during the follow-up; 4) persistent MetS: participants who had MetS both at baseline and follow-up. Results: The mean follow-up time was 6.1 years. There were 176 subjects in the non-MetS group, 35 in the incident MetS group, 41 in the recovery MetS group, and 88 in the persistent MetS group. Increases in the levels of both hs-CRP 1.40 (95% CI: 1.15, 1.71, p = 0.001) and IL-6 1.09 (95% CI: 1.03, 1.17, p = 0.004) significantly increased the odds of the incident and persistent MetS, respectively. The area under the ROC curve (AUC) was more than 0.69 (p

The possible association of habitual physical activity (PA) and the risk of pre-diabetes (Pre-DM) progression to type 2 diabetes (T2D) or the chance of returning to normoglycemia was investigated. This cohort study included 1167 Pre-DM individuals (mean age of 53.5 years, and 45.3% men) who participated in the third phase of the Tehran Lipid and Glucose Study (2006–2008) and followed up to a median of 9 years. PA, including leisure time and job activities, was measured using a reliable and validated Iranian version of the Modifiable Activity Questionnaire and reported as metabolic equivalent (MET)-minutes per week. The odds ratios (ORs) and 95% confidence intervals (CIs) of incident T2D and returning to normoglycemia were estimated in relation to PA levels (i.e., per every 500 MET-minutes/week, or across categories of PA levels 1500 MET-minutes/week). During the study follow-up, 39.0 % progressed to T2D, and 37.8% returned to normoglycemia. Compared to subjects with a PA 1500 MET-minutes/week. We further noted that each 500 MET-min/week activity corresponded to an elevated chance of returning to normoglycemia by 5% (OR = 1.05, 95% CI = 1.01–1.11). The study’s findings provided evidence that higher daily PA levels may facilitate Pre-DM regression to normoglycemia. The beneficial effect of PA in Pre-DM subjects needs to exceed the recommended levels (i.e., 600 MET-minutes/week).

ABSTRACT Objective: Recent studies investigated the role of amino acids (AAs) in weight management. We aimed to determine the association between AAs and three-year change of anthropometric indices and incident obesity. Materials and methods: Height, weight, hip, and waist circumference (WC) were collected at baseline and follow up. Three-year changes in anthropometric indices and obesity incident according to body mass index (BMI) (overweight & obesity) and WC cutoffs (obesity-WC) were ascertained. Dietary intakes of AAs were collected at baseline, using a food frequency questionnaire. Data analyses were conducted on 4976 adult participants and two subsamples, including 1,570 and 2,918 subjects, for assessing the AAs relationship with 3-year changes on anthropometric indices and obesity incident. Results: Lysine and aspartic acid were positively associated with higher weight change, whereas acidic AAs, cysteine, and glutamic acid showed a negative correlation with weight change. Furthermore, a weak positive correlation was shown for alkaline AAs, lysine, and valine with WC; however, acidic AAs, tryptophan, cysteine, and glutamic acid were negatively associated with WC. Aromatic and acidic AAs also demonstrated a weak negative relation with changes in BAI. Phenylalanine and Aromatic AAs showed a negative association with overweight &obesity incidence adjusting for potential confounders. Each quartile increases the dietary lysine, arginine, alanine, methionine, aspartic acid, and alkaline AAs related to a greater risk of obesity-WC, while tryptophan, glutamic acid, proline, and acidic AAs associated with lower obesity-WC risk. Conclusion: Our results suggested that certain dietary AAs may potentially change anthropometric indices and risk of obesity incident.

Abstract Background We investigated the impact of weight change on mortality in a population-based cohort setting. Methods We conducted two weight measurements for 5436 participants aged ≥ 30 years with an approximate 3-year interval. Based on their weight change, we categorized participants to: > 5% weight loss, 3–5% weight loss, stable weight (± 5% weight gain. We followed participants for mortality annually up to March 20th 2018. We applied the multivariable Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of weight change categories for all-cause, cardiovascular (CV), and cancer mortality, considering stable weight as reference. The Cox models was adjusted for age, sex, educational level, body mass index, smoking status, hypertension, hypercholesterolemia, diabetes, and cardiovascular disease (CVD) at baseline. Results During a median follow-up of 14.4 years, 629 deaths (247 CV and 126 cancer deaths) have occurred. Over 5% weight loss and gain were associated with increased risk of all-cause mortality in multivariable analysis with HRs of 1.47 [95% CI: 1.17–1.85] and 1.27 [1.02–1.57], respectively; however, a 3–5% loss or gain did not alter the risk of all-cause mortality significantly. These significant risks for wight change > 5% were not modified by the presence of diabetes, obesity, and smoking status; however, the unfavorable impact of weight change on mortality events was more prominent in those older than > 65 years (P-value for interaction: 0.042). After excluding those with history of CVD, diabetes, and cancer during the weight measurements period, these associations significantly attenuated (HR: 1.29 [0.89–1.87] for > 5% weight loss and 1.12 [0.84–1.50] for > 5% weight gain). Additionally, a > 5% weight loss was also associated with about 60% higher risk for CV mortality (HR: 1.62 [1.15–2.28]), and a 3–5% weight loss was associated with about 95% higher risk of cancer mortality (HR: 1.95 [1.13–3.38]). Conclusions Our findings showed a U-shaped association across weight change categories for all-cause mortality risk with over 5% weight gain and loss causing higher risk. Moreover, weight loss can have adverse impact on CV and cancer mortality events.

Abstract Background Body dissatisfaction has been known as an important public health concern that can influence the physical and psycho-social health of adolescents. Hence, health professionals need a valid and reliable tool to assess this problem and its related factors in youth. This study aims to develop and assess the psychometric properties of an indigenous scale for the evaluation of body image and to investigate its association with body weight status among Iranian adolescents. Methods This study was conducted on 857 adolescents who completed the body image scale for Youth (BISY) and self-reported their body weight and height. Face, content, and construct validity methods were used to assess the validity of the BISY. Exploratory factor analysis (EFA) was used to assess construct validity. Moreover, the internal consistency of the scale was assessed by calculating Cronbach’s alpha coefficient (α), and test–retest reliability was examined using the intra-class correlation coefficient (ICC). To compare the BISY scores across sex and body weight status groups, the Independent samples t-test and the analysis of variance (ANOVA) or Welch tests were used, respectively. Results Mean age and body mass index (BMI) of participants were 16.5 ± 1.1 years and 22.4 ± 4.5 kg/m2, respectively. The EFA showed a 10-factor construct which explained 57% of the variance. The Cronbach’s alpha coefficient for overall items of the scale was 0.896 and ranged from 0.42 to 0.92 for subscales. The test–retest reliability result was acceptable for the BISY (ICC = 0.805). The ICC values ranged from 0.753 to 0.990 for BISY subscales. The BISY total score was significantly higher in girls compared to boys (34.8 ± 12.7 vs. 31.3 ± 10.2; p

Abstract Background Among candidate genes related to type 2 diabetes (T2DM), one of the strongest genes is Transcription factor 7 like 2 (TCF7L2), regarding the Genome-Wide Association Studies. We aimed to conduct a systematic review of the literature on the modification effect of TCF7L2 on the relation between glycemic parameters and lifestyle factors. Methods A systematic literature search was done for relevant publications using electronic databases, including PubMed, EMBASE, Scopus, and Web of Science, from January 1, 2000, to November 2, 2021. Results Thirty-eight studies (16 observational studies, six meal test trials, and 16 randomized controlled trials (RCTs)) were included. Most observational studies had been conducted on participants with non-diabetes showing that TCF7L2 modified the association between diet (fatty acids and fiber) and insulin resistance. In addition, findings from meal test trials showed that, compared to non-risk-allele carriers, consumption of meals with different percentages of total dietary fat in healthy risk-allele carriers increased glucose concentrations and impaired insulin sensitivity. However, ten RCTs, with intervention periods of less than ten weeks and more than one year, showed that TCF7L2 did not modify glycemic parameters in response to a dietary intervention involving different macronutrients. However, two weight loss dietary RCTs with more than 1-year duration showed that serum glucose and insulin levels decreased and insulin resistance improved in non-risk allele subjects with overweight/obesity. Regarding artichoke extract supplementation (ALE), two RCTs observed that ALE supplementation significantly decreased insulin concentration and improved insulin resistance in the TT genotype of the rs7903146 variant of TCF7L2. In addition, four studies suggested that physical activity levels and smoking status modified the association between TCF7L2 and glycemic parameters. However, three studies observed no effect of TCF7L2 on glycemic parameters in participants with different levels of physical activity and smoking status. Conclusion The modification effects of TCF7L2 on the relation between the lifestyle factors (diet, physical activity, and smoking status) and glycemic parameters were contradictory. PROSPERO registration number CRD42020196327

Background Recent evidence recommended stepwise screening methods for identifying individuals at high risk of type 2 diabetes to be recruited in the lifestyle intervention programs for the prevention of the disease. This study aims to assess the performance of different stepwise screening methods that combine non-invasive measurements with lab-based measurements for identifying those with 5-years incident type 2 diabetes. Methods 3037 participants aged ≥30 years without diabetes at baseline in the Tehran Lipid and Glucose Study (TLGS) were followed. Thirty-two stepwise screening methods were developed by combining a non-invasive measurement (an anthropometric measurement (waist-to-height ratio, WtHR) or a score based on a non-invasive risk score [Australian Type 2 Diabetes Risk Assessment Tool, AUSDRISK]) with a lab-based measurement (different cut-offs of fasting plasma glucose [FPG] or predicted risk based on three lab-based prediction models [Saint Antonio, SA; Framingham Offspring Study, FOS; and the Atherosclerosis Risk in Communities, ARIC]). The validation, calibration, and usefulness of lab-based prediction models were assessed before developing the stepwise screening methods. Cut-offs were derived either based on previous studies or decision-curve analyses. Results 203 participants developed diabetes in 5 years. Lab-based risk prediction models had good discrimination power (area under the curves [AUCs]: 0.80-0.83), achieved acceptable calibration and net benefits after recalibration for population’s characteristics and were useful in a wide range of risk thresholds (5%-21%). Different stepwise methods had sensitivity ranged 20%-68%, specificity 70%-98%, and positive predictive value (PPV) 14%-46%; they identified 3%-33% of the screened population eligible for preventive interventions. Conclusion Stepwise methods have acceptable performance in identifying those at high risk of incident type 2 diabetes.

Abstract 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

BackgroundHypertension (HTN) is known to be the leading cause of cardiovascular disease (CVD) and mortality. We aimed to assess the impact of changes in 3 years in different blood pressure (BP) categories on incident CVD.MethodsIn this study, 3,685 Tehranians aged ≥30 years (42.2% men) free of prevalent CVD with BP level

ObjectivesThe aim of the study was to investigate the effect of treatment on pregnancy outcomes among women who had fasting plasma glucose (FPG) 5.1-5.6 mmol/l in the first trimester of pregnancy.MethodsWe performed a secondary-analysis of a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. All pregnant women with FPG values range 5.1-5.6 mmol/l in the first trimester of gestation were included in the present study (n=3297) and classified to either the (i) intervention group who received treatment for GDM along with usual prenatal care (n=1,198), (ii) control group who received usual-prenatal-care (n=2,099). Macrosomia/large for gestational age (LGA) and primary cesarean-section (C-S) were considered as primary-outcomes. A modified-Poisson-regression for binary outcome data with a log link function and robust error variance was used to RR (95%CI) for the associations between GDM status and incidence of pregnancy outcomes.ResultsThe mean maternal age and BMI of pregnant women in both study groups were similar. There were no statistically significant differences in the adjusted risks of adverse pregnancy outcomes, including macrosomia, primary C-S, preterm birth, hyperbilirubinemia, preeclampsia, NICU-admission, birth trauma, and LBW both groups.ConclusionsIt is found that treating women with first-trimester FPG values of 5.1-5.6 mmol/l could not improve adverse pregnancy outcomes including macrosomia, Primary C-S, Preterm birth, hypoglycemia, hypocalcemia, preeclampsia, NICU admission, Birth trauma and LBW. Therefore, extrapolating the FPG cut-off point of the second trimester to the first –which has been proposed by the IADPSG, might therefore not be appropriate.Clinical Trial Registrationhttps://www.irct.ir/trial/518, identifier IRCT138707081281N1.

BackgroundThe 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.MethodsThe 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).ResultsDuring 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).ConclusionAmong 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.

Abstract Ideal cardiovascular health (CVH) is associated with a lower risk of developing cardiovascular diseases. This study aims to investigate the association of CVH metrics with carotid intima-media thickness (cIMT) as a marker of subclinical atherosclerosis in young adults. A cross-sectional study was performed on 1295 adults, average age of 29.7 ± 4.0 years, selected from the participants of the Tehran Lipid and Glucose Study. The participants were divided into three groups based on the overall CVH score: ideal, intermediate, and poor CVH. Multivariate-adjusted linear regression was used to determine the association of the CVH score with cIMT. Multivariate-adjusted odds ratios (ORs) were calculated for high cIMT (≥ 95% percentile). Also, the independent effects of each ideal CVH metric on cIMT were analyzed. The prevalence of ideal CVH was 6.4% in men and 12.4% in women, and mean cIMT was obtained 0.53 ± 0.09 mm in men and 0.57 ± 0.08 mm in women. A 1-point increase of the CVH score in men and women was associated with a cIMT decrease of 0.009 and 0.011 mm (men: Beta [SE] = − 0.009 [0.003]; women: − 0.011 [0.007], p

Abstract Background The long-term effectiveness of healthy lifestyle interventions on improving leisure-time physical activity (LTPA) in adolescents and its factors in low- and middle-income communities is unclear. This study is the first to investigate LTPA trends in a population of Iranian adolescents who underwent a multi-setting lifestyle intervention, considering sex and the time of intervention onset. Methods Participants were 2374 adolescents (57.2% girls), aged 12–18 years, who participated in the Tehran Lipid and Glucose Study (TLGS) during 1999–2001 and followed for a median follow-up of 15.9 over five data points every 3 years. Adolescent participants were assigned to the intervention or control groups based on their residential areas. Boys and girls were categorized into 12–15 or 16–18 years old to minimize participants’ bio-psychological differences, facilitate environmental interventions by more compliance with the Iranian educational system and identify the best time to start the intervention. All adolescents in the intervention area received healthy lifestyle interventions via the school-, family-, and community-based programs. LTPA was assessed using the reliable and validated Iranian Modifiable Activity Questionnaire (MAQ) version over the five data points. The Generalized Estimating Equations method was used to evaluate educational intervention’s effect on LTPA in adolescents during the follow-up. Results In boys who experienced the early onset of intervention (12–15 years), the interaction effect of follow-up examinations and the intervention was significant where the impact of the intervention differed over time. In this group, LTPA was higher in the control group than in the intervention group at the first follow-up examination (β = − 1088.54). However, an increasing trend of LTPA was observed in the intervention group until the third follow-up examination (β = 1278.21, p = 0.08, and β = 1962.81, p = 0.02, respectively), with borderline significance levels at the 2nd (P = 0.08) and the 4th (P = 0.08) measurements. The interaction terms and main effects of intervention and follow-up examinations were not significant in boys with late intervention onset. Although older boys in the intervention group had higher LTPA than the control group, there were no significant differences among study groups in all follow-up examinations. Regarding girls, LTPA did not differ significantly between intervention and control groups in all follow-up examinations (P > 0.05). Conclusion Our results showed that a multi-setting practical lifestyle intervention could improve long-term energy expenditure in LTPA in adolescent boys who have experienced an early onset intervention. Findings emphasized the vital role of gender and the onset of these interventions. The current results would be valuable to plan tailored interventions to improve LTPA and community health. Trial registration This study is registered at Iran Registry for Clinical Trials (IRCT), a WHO primary registry ( http://irct.ir ). The TLGS clinical trial was the very first registration in the IRCT (Iran Registry of Clinical Trials). it was registered on 2008-10-29 by the registration number IRCT138705301058N1 . Based on the international committee of medical journal Editors (ICMJE), “retrospective registration” is acceptable for trials that began before July 1, 2005.

Abstract Background This study aimed to investigate the effects of legumes in dietary approaches to stop hypertension (DASH) on blood pressure and urinary sodium and potassium in participants with type 2 diabetes. We further investigated whether changes in individual dietary food groups in the DASH diet contribute to blood pressure. Methods Participants were randomized to the traditional DASH diet (n = 150) or the legume-based DASH diet (n = 150). Blood pressure and urinary sodium and potassium were measured at baseline and after 16-week interventions. An intention-to-treat approach with multiple imputations of missing data was applied. The restricted cubic spline (RCS) was applied to assess the linearity and explore the shape of the relationship between the changes in food groups and systolic blood pressure (SBP) in the two intervention groups. Results A reduction in SBP and urinary sodium was observed at week 16 in both dietary interventions, and this reduction was more significant in the legume-based DASH diet, than in the DASH diet. In the legume-based DASH diet, SBP decreased with the legume intake of more than 95.8 g/day (P nonlinear

Abstract Background Previous studies have cited insulin-related disorders, including hyperinsulinemia, as one of the main causes of obesity risk and metabolic disorders. We aimed to investigate the association of the Empirical Dietary Index for Hyperinsulinemia (EDIH) and Empirical Lifestyle Index for Hyperinsulinemia (ELIH) with the risk of obesity phenotypes among Iranian adults. Methods Present study was conducted on 2705 subjects, including 1604 metabolically healthy normal weights (MHNW) and 1101 metabolically healthy obesity (MHO) individuals. Obesity phenotypes, including MHNW, MHO, metabolically unhealthy normal weights (MUNW), and metabolic unhealthy obesity (MUO), were determined using the criteria of the Joint International statement (JIS) for metabolic syndrome. Dietary intake data from the previous year was gathered using a food frequency questionnaire. Cox proportional hazard regression was used to estimate the hazard ratio and 95% confidence intervals (HRs and 95% CIs) of obesity phenotypes incident across tertiles of EDIH and ELIH scores. Results The mean ± SD of age and BMI of all participants were 33.5 ± 12.2 years and 24.3 ± 3.8 kg/m2, respectively. In the multivariable-adjusted model, a higher ELIH score was associated with a greater risk for incidence of MUO (HR: 3.47, 95%CI: 2.54–4.74; Ptrend =

Abstract Backgrounds This randomized controlled trial aimed to investigate the effects of replacing red meat with legumes in the dietary approach to stop hypertension (DASH) diet on inflammatory markers over 16 weeks in overweight and obese individuals with type 2 diabetes. Also, the modulatory effects of TCF7L2 rs7903146 variant on this effect were assessed. Methods In this trial, 300 participants with type 2 diabetes, aged 30–65 years with an identified TCF7L2 rs7903146 genotype, were studied. The participants were randomly assigned to the DASH diet or the legume-based DASH diet over 16 weeks. In the DASH diet group, the participants were instructed to follow the standard DASH diet. The legume-based DASH diet was similar to the standard DASH diet, with the exception that one serving of red meat was replaced with one serving of legumes at least five days a week. At the beginning of the study and 16-week follow-up, venous blood samples were collected from all participants who fasted for 12–14 h overnight. The serum concentration of High-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) was measured using an enzyme-linked immunosorbent assay (ELISA) kit. Also, the serum malondialdehyde (MDA) concentration was assessed based on a colorimetric method using a commercial kit. The primary outcome was the difference in hs-CRP changes between the diets. A secondary outcomes was the difference in IL-6, TNF-α, and MDA between the groups among total population and based on TCF7L2 rs7903146 risk allele (CT + TT) and non-risk allele (CC) separately. Results The hs-CRP level reduced in the legume-based DASH diet group as compared to the DASH diet group in the 16-week follow-up group. The levels of TNF-α, IL-6, and MDA reduced after the legume-based DASH diet relative to the DASH diet. Reduction of inflammatory markers was observed in both carriers of rs7903146 risk allele and non-risk allele. Conclusions Substituting one serving of red meat with one serving of legumes in DASH diet, at least five days a week, could improve the hs-CRP, TNF-α, IL-6, and MDA in participants with type 2 diabetes regardless of having rs7903146 risk or non-risk allele. Trial registration IRCT, IRCT20090203001640N17.

Abstract Background Patients with type-2 diabetes mellitus (T2DM), have a higher risk of future cardiovascular diseases (CVD). Meanwhile, probiotics are shown to positively impact CVD-related parameters. This randomized controlled trial sought to evaluate the effects of probiotic supplementation on fundamental CVD-related parameters including atherogenic index of plasma (AIPs), blood pressure, the Framingham risk score, and antioxidant markers in patients with T2DM. Methods Eligible participants were randomly assigned to receive 2 capsules/day of probiotics [each containing 500 mg of L.acidophilus(5 × 1010 CFU/g), L.plantarum(1.5 × 1010 CFU/g), L.fermentum(7 × 109 CFU/g), L.Gasseri(2 × 1010 CFU/g) and 38.5 mg of fructo-oligo-saccharides], or placebo for 6 weeks. Systolic and diastolic blood pressures (SBP and DBP, respectively), mean arterial blood pressure (MAP), atherogenic indices (the ratios of TC/HDL-C, LDL-C/HDL-C, and logTG/HDL-C), the 10-year Framingham CVD risk score, as well as total anti-oxidant capacity (TAC), paraoxonase (PON) and total oxidant status (TOS) were evaluated before and after the study. Final analyses were adjusted based on baseline parameters, and potential covariates including age, sex, PUFA and sodium intakes. Results Sixty participants completed the study. Compared with placebo, probiotic supplementation resulted in a significant decrease in SBP[-9.24 mmHg(− 14.5, − 3.9)], DBP[− 3.71 mmHg(− 6.59, − 0.83)], MAP[− 5.55 mmHg(− 8.8, − 2.31)], the Framingham risk categories [medium–low(1.5) vs. 2 (medium)] and logTG/HDL-C ratio [− 0.08 (− 0.14, 0)] (All P

Introduction: The association between subclinical hypothyroidism (SCH) and gestational diabetes (GDM) is controversial. This study was performed with aim to compare the incidence of GDM in women with SCH and euthyroid women. Methods: In this prospective study, data obtained from 1026 pregnant women (including 683 cases of euthyroid and 343 women with SCH) participating in the cohort study of Tehran thyroid and pregnancy (TTP) was used. Serum levels of thyrotropin (TSH), thyroxine (T4), T3-uptake, and thyroid peroxidase antibody (TPOAb) were measured at first visit of the first trimester of pregnancy; based on this, euthyroid and SCH women were identified. These two groups were evaluated for gestational diabetes. Data were analyzed using STATA software (version 13). The continuous variables were compared between the two groups using independent t-test and Mann-Whitney test, and categorical variables using chi-square test or Fisher's exact test. Log-binomial model was used to identify the effect of SCH and levothyroxine on GDM. P< 0.05 was considered statistically significant Results: There was no significant difference in the incidence of GDM in SCH women compared to the control group either in the unadjusted model or after adjusting for the effective risk factors. Also, there was no significant difference in the incidence of GDM between SCH with TPOAb+, SCH with TPOAb-, and euthyroid groups. The risk of GDM in the TPOAb positive group was not significantly different from TPOAb negative group. Serum TSH (p=0.9), T4 (p=0.8), T3-uptake (p=0.7), and TPOAb (p=0.4) levels were not significantly different between the GDM and non-GDM groups. Conclusion: Although no significant association was found between GDM and SCH in this study, however, it seems that due to various factors affecting the incidence of SCH and GDM, such as different diagnostic criteria and reference values, proving this issue requires further studies.

Abstract 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

Abstract Objective To examine the association of age, period, and birth cohort with body mass index (BMI) and waist circumference (WC) changes among the participants of the Tehran Lipid and Glucose Study from 1999 to 2015. Methods This prospective cohort study included 4895 participants aged ≥20 years (41.3% men), who were divided into twelve gender stratified groups, having a ten-year age difference between them. Analyses were conducted to explicitly assess the association of age vs. period on BMI and WC changes. In addition, we evaluated BMI and WC changes among different birth cohorts. Results Upon 15 years of follow-up, the mean BMI of men and women increased from 26.0 ± 3.9 to 27.5 ± 4.3 kg/m2 and from 27.5 ± 4.8 to 29.9 ± 5.4 kg/m2 (P trend

Abstract 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.

Highlights The associations between diastolic blood pressure and stroke events were stronger in men than women. The fasting blood plasma level was associated with higher risk of stroke events in men than women. Hypertension and diabetes were associated with higher risk of stroke events in men than women. The association between systolic blood pressure with ischemic stroke was higher in men than women.

Abstract Background We aimed to estimate salt intake among an Iranian population using spot urine-based equations and a dietary-based method. Methods Adult men and women (n = 2069) were recruited from the Tehran Lipid and Glucose Study (2014–2017). Urinary sodium (Na), potassium (K), and creatinine (Cr) concentrations were measured in the morning spot urine samples. The 24-h urinary Na excretion and predicted salt intake was estimated using five equations, i.e., Kawasaki, Tanaka, Intersalt, Toft, and Whitton. A validated food frequency questionnaire (FFQ) was used to obtain dietary intake of salt. The agreement of each urinary- and FFQ-based salt estimation with the overall mean of the methods, considered as the gold standard, was assessed using the Bland–Altman method. Results Mean age of the participants was 45.6 ± 14.8 y, and 45.4% were men. Mean (SD) estimated salt intake, derived from the overall mean of the methods, was 9.0 ± 2.2 g/d (10.2 ± 2.1 and 7.9 ± 1.7 g/d in men and women, respectively). Mean bias of the estimations from the overall mean ranged from − 0.2.42 to 2.75 g/d, with the Tanaka equation having the least bias (mean bias = 0.13 ± 1.10, 95% CI − 2.37, 2.30 g/d). Tanaka estimated a mean salt intake of 8.9 g/d (range 2.1 to 18.7 g/d); accordingly, only 5.1% of participants adhered to the recommendation (

Abstract Background and aim Hydrogen sulfide (H2S), a signaling gasotransmitter, is involved in carbohydrate metabolism. Here, we aimed to assess the potential association between serum H2S and dysglycemia in the framework of a population-based study. Methods Adults men and women with completed data (n = 798), who participated in the Tehran Lipid and Glucose Study (2014–2017) were included in the study. Medians of fasting serum H2S concentration were compared across the glycemic status of the participants, defined as type 2 diabetes mellitus (T2DM), isolated impaired fasting glucose (IIFG), isolated impaired glucose tolerance (IIGT), combined IFG-IGT, and normal glycemia [i.e., those with both normal fasting glucose (NFG) and normal glucose tolerance (NGT)]. Multinomial logistic regression was used to assess potential associations between serum H2S and the defined glycemic status. Results Mean age of the participants was 45.1 ± 14.0 y, and 48.1% were men. Prevalence of T2DM, IIFG, IIGT, and combined IFG-IGT was 13.9, 9.1, 8.1, and 4.8% respectively. No significant difference was observed in serum H2S concentrations between the groups. Lower serum H2S (

Abstract Background and aim The potential cardiovascular impact of usual intakes of oxalate (Ox) is uninvestigated. We evaluated the effect of dietary Ox and its interaction with dietary calcium (Ca) on incident cardiovascular disease (CVD). Methods We included 2966 adult men and women aged 19–84 y without known CVD during baseline enrollment (2006–2008) of the Tehran Lipid and Glucose Study. Dietary intakes were assessed using a validated FFQ, and incident CVD (i.e., coronary heart disease, stroke, and CVD mortality) were documented through March 2018. Results A 7.1% incident of CVD occurred during a median follow-up of 10.6 y. After multivariable adjustment for traditional risk factors and key dietary nutrients, including total fat and fiber, Ox intakes ≥220 mg/d increased incident CVD (HR T3 vs. T1 = 1.47, 95% CI = 1.02–2.12). This association was potentiated (HR T3 vs. T1 = 2.42, 95% CI = 1.19–4.89) in subjects who had a lower intake of Ca (

Abstract Background Assessing the risk of cardiovascular disease (CVD) is crucial in preventive cardiology. We aimed to determine the trend of CVD risk among individuals with and without diabetes during two decades of follow-up in a Middle Eastern cohort. Methods We studied 8,450 individuals (55.5% women) aged 40–75 years who participated in the Tehran Lipid and Glucose Study (TLGS). Diabetes status and CVD risk factors were evaluated in six examinations from 1999 to 2018. The individual 10-year CVD risk score was calculated using the ACC/AHA recommended risk equation. We used generalized estimating equation models (GEE) to assess the time trends of CVD risk factors and CVD risk scores in diabetic and non-diabetic groups separately. Results The age-adjusted ACC/AHA risk score significantly decreased in non-diabetic women and men (from 3.2% to 1.6% in women and 6.8% to 5.0% in men; p for trend

BackgroundConsidering the importance of cardiovascular disease (CVD) risk prediction for healthcare systems and the limited information available in the Middle East, we evaluated the SCORE and Globorisk models to predict CVD death in a country of this region.MethodsWe included 24 427 participants (11 187 men) aged 40-80 years from four population-based cohorts in Iran. Updating approaches were used to recalibrate the baseline survival and the overall effect of the predictors of the models. We assessed the models’ discrimination using C-index and then compared the observed with the predicted risk of death using calibration plots. The sensitivity and specificity of the models were estimated at the risk thresholds of 3%, 5%, 7%, and 10%. An agreement between models was assessed using the intra-class correlation coefficient (ICC). We applied decision analysis to provide perception into the consequences of using the models in general practice; for this reason, the clinical usefulness of the models was assessed using the net benefit (NB) and decision curve analysis. The NB is a sensitivity penalized by a weighted false positive (FP) rate in population level.ResultsAfter 154 522 person-years of follow-up, 437 cardiovascular deaths (280 men) occurred. The 10-year observed risks were 4.2% (95% CI: 3.7%-4.8%) in men and 2.1% (1.8-2%.5%) in women. The c-index for SCORE function was 0.784 (0.756-0.812) in men and 0.780 (0.744-0.815) in women. Corresponding values for Globorisk were 0.793 (0.766-0.820) and 0.793 (0.757-0.829). The deviation of the calibration slopes from one reflected a need for recalibration; after which, the predicted-to-observed ratio for both models was 1.02 in men and 0.95 in women. Models showed good agreement (ICC 0.93 in men, and 0.89 in women). Decision curve showed that using both models results in the same clinical usefulness at the risk threshold of 5%, in both men and women; however, at the risk threshold of 10%, Globorisk had better clinical usefulness in women (Difference: 8%, 95% CI: 4%-13%).ConclusionOriginal Globorisk and SCORE models overestimate the CVD risk in Iranian populations resulting in a high number of people who need intervention. Recalibration could adopt these models to precisely predict CVD mortality. Globorisk showed better performance clinically, only among high-risk women.

Abstract 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

Abstract Background The combined roles of lifestyle factors in the risk of type 2 diabetes (T2D) are not fully investigated. In the present study, we aimed to assess the relationship between a healthy lifestyle score (HLS) and the risk of T2D in Tehranian adults. Methods A total of 3859 individuals without T2D were recruited from participants of the Tehran Lipid and Glucose Study (2009–2011) who were followed up for a mean period of 6 years. A food frequency questionnaire was used to collect individuals' dietary intakes at baseline. HLS scores was calculated based on three pre-defined methods with focusing on 4 lifestyle factors including, no current smoking, no obesity, high physical activity, and greater adherence to the healthy diet[determined using the alternate healthy eating index-2010(AHEI-2010), modified French Programme National Nutrition Santé-Guideline Score(mPNNS-GS), and healthy diet pattern score(HDP)]. Results Mean ± SD age of participants(44.4% men) was 41.1 ± 12.3 years. After 6-year follow-up of study, 295(7.6%) new cases of T2D were reported. Based on the age and sex-adjusted model, an inverse association was observed between the higher score of HLS-AHEI-2010 (OR = 0.24;95%CI:0.10–0.60), HLS-mPNNS-GS (OR = 0.28;95%CI:0.15–0.50), and HLS-HDP (OR = 0.39;95%CI:0.24–0.64) and the risk of T2D (P for trend

Abstract Background Several studies have assessed the association between dietary choline and betaine and cardiovascular disease (CVD), but their results are inconsistent. The present study aimed to determine the association between dietary intake of choline and betaine and the risk of CVD in the general population over a 10.6-year period of follow-up. Methods The present cohort study was conducted on participants in the third wave of the Tehran Lipid and Glucose Study (2006–2008) and was followed-up until March 2018. Dietary intake of choline and betaine was calculated using the United States Department of Agriculture (USDA) database. Patients’ medical records were used to collect data on CVD. Results In this study, 2606 subjects with no previous CVD participated and were followed-up for a median of 10.6 years. During the follow-up periods, 187 incidences of CVD were detected. Results of the Cox proportional hazards regression indicated that neither energy-adjusted total choline nor betaine was associated with the incidence of CVD. Among individual choline forms, only higher intake of free choline (FC) was associated with a lower risk of CVD (HR: 0.64, 95% CI: 0.42–0.98). There was no significant association between each 10 mg/d increase in choline and betaine content of each food category and CVD. Conclusion Our investigation indicates no association between energy-adjusted total choline and betaine and a 10.6-year risk of CVD among adults. Besides, we found no relationship between individual choline forms (except FC) and CVD. We also found energy-adjusted choline and betaine obtained from food categories were not associated with the risk of CVD.

Abstract Background There is no study regarding developing a valid index to predict insulin-related disorders in the Iranian population based on their dietary habits and lifestyle. In the current study, we aimed to develop and validate insulinemic potential indices of diet and lifestyle in Iranian adults. Methods In this cross-sectional study, we analysed data of 1063 men and women aged ≥ 25 years among participants of the examination three of Tehran lipid and glucose study (TLGS) (2006–2008). Dietary intakes were assessed using a valid semi-quantitative food frequency questionnaire. Dietary and lifestyle indices were developed using stepwise linear regression analysis based on dietary intakes, body mass index, and physical activity data. Fasting serum insulin concentration and homeostatic model assessment for insulin resistance (HOMA-IR) were used as biomarkers of hyperinsulinemia (HI) and insulin resistance (IR). Validation analyses were performed in examination four of TLGS. Results We developed four indices related to insulin homeostasis, including the dietary index for HI (DIH), the dietary index for IR (DIR), the lifestyle index for HI (LIH), and the lifestyle index for IR (LIR). Based on multivariable-adjusted models, the relative values of the biomarker in subjects in the highest quartile of indices were 45% for LIH (95% CI 1.36–1.55, Ptrend

Abstract Cardiovascular disease (CVD), as the leading cause of death worldwide, is the collective term named for disorders afflicting the blood vessels and heart. Inflammation and enhanced oxidative stress have been shown as fundamental risk factors in the onset and progression of CVD. Chronic inflammatory conditions attenuate blood levels of antioxidants because of the continuous generation of elevated levels of reactive oxygen species (ROS). A sufficient intake of antioxidants is also suggested to beneficially interfere with CVD by quenching ROS. Antioxidant vitamins and minerals, such as vitamins A, E, and C, and zinc may slow the development and progression of CVD. This study aimed at investigating the association between daily consumption of dietary vitamins A, E, and C, and zinc and the incidence of CVD. Eligible adults (n = 5102) aged ≥ 30 years, were selected from the participants of the Tehran lipid and glucose study with an average follow-up of 5.3 years. Dietary intake was assessed using a valid and reliable semi-quantitative food frequency questionnaire. Anthropometrics and biochemical variables were evaluated at baseline and follow-up examinations. Multivariable Cox proportional hazard regression models were used to estimate the development of CVD associated with total intakes of vitamins A, E, and C, and zinc. This study was conducted on 2253 men and 2849 women aged 47.0 ± 11.6 and 45.6 ± 10.5 years, respectively. The main sources of dietary vitamins A, E, and C and zinc were fruits, vegetables, and legumes. Risk of CVD decreased from quartile 1 to quartile 4 for vitamin E intake (HR 1.00, 0.91, 0.77, and 0.57; P trend = 0.03). The association between the risk of CVD and quartiles of vitamins A, and C and zinc intake was not statistically significant. Our study suggests an inverse association between vitamin E intake and the risk of CVD, emphasizing the potential protective role of fruit and vegetable in the prevention of CVD.

BackgroundThere is debate regarding which anthropometric indices is the most appropriate predictor of cardiovascular disease (CVD) among adolescents. The purpose of this study was to investigate the association of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) in adolescents with high carotid intima-media thickness (cIMT) in early adulthood, as the surrogate marker of CVD in a cohort study.MethodsA total of 875 Iranian adolescents (female = 421) aged 10–17 years old were entered the study. The cIMT was measured in early adulthood (20–38 years old) after 18.2 (median) years of follow-up and defined as > 90th percentile for sex and age groups. The gender specific association between a 1-SD increase in each anthropometric measures with high cIMT was examined using multivariate logistic regression analysis adjusted for age, smoking, family history of CVD, systolic blood pressure, total cholesterol, and fasting blood sugar. In the multivariable analysis, the interaction between sex and age groups with anthropometric measures were significant (all p-values < 0.05).ResultsAmong males, all anthropometric measures including BMI, WC, WHR, and WHtR were associated with high cIMT; the corresponding odds ratios were 1.43 (1.05–1.94), 1.63 (1.22–2.19), 1.33 (1.03–1.71), and 1.41 (1.07–1.87), respectively. However, after considering the related adulthood anthropometric measurements, the association remained significant for WC 1.48 (1.04–2.10) and WHR [1.28 (0.99–1.66), P = 0.06]. Moreover, among early adolescent boys aged 10–14 years, all of the anthropometric measures were significantly associated with high cIMT in the multivariate analysis that included the related adulthood anthropometric measures. The area under the curve (AUC) for the anthropometric measurements among males ranged from 0.576 for WHtR up to 0.632 for WC, without any superiority between them. Among females, only in linear regression analysis, a significant association were found between the higher value of WC and WHtR with cIMT measurement in adulthood; however, the risk reached to null after considering adult anthropometric measures.ConclusionGeneral and central obesity measures were significantly associated with high cIMT only among Iranian male adolescents, the relationship that were more prominent among pre-pubertal males.

Introduction: The current longitudinal 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 with health-related quality of life (HRQoL) throughout an 18-year period. Methods: 1932 participants (649 men and 1283 women) who completed the HRQoL questionnaire during 2016-2019 were recruited in the current investigation. Based on the body mass index (BMI) 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 PCS scores of both sexes and MCS scores just in women (P value=

ObjectivesThere is considerable worldwide controversy regarding optimal screening and diagnostic approaches for GDM. This study aimed to compare the prevalence, maternal and neonatal outcomes of a One-step with a Two-step approach for the screening and diagnosis of GDM in a large community sample of pregnant women.MethodsWe conducted a secondary analysis of a randomized community non-inferiority trial of GDM screening in Iran. For the current study, all pregnant women who met the inclusion criteria were randomized into two groups for GDM screening. The first group of women (n = 14611) was screened by a One-step screening approach [75-g 2-h oral glucose tolerance test (OGTT)] and the second group (n = 14160) by a Two-step method (the 50-g glucose challenge test followed by the 100-g OGTT). All study participants were followed up until delivery, and the adverse maternal and neonatal outcomes were recorded in detail.ResultsGDM was diagnosed in 9.3% of the pregnant women who were assigned to the One-step and in 5.4% of those assigned to the Two-step approach with a statistically significant difference between them (p < 0.001). Intention-to-treat analyses showed no significant differences between the One-step and the Two-step group in the unadjusted risks of the adverse pregnancy outcomes of macrosomia, primary cesarean-section, preterm birth, hypoglycemia, hypocalcemia, hyperbilirubinemia, preeclampsia, neonatal intensive care unit admission, birth trauma, low birth weight, and intrauterine fetal death. Results remained unchanged after adjustment for potential confounder variables including gestational age at enrollment and delivery, maternal body mass index, gestational weight gain, type of delivery, treatment modality, and GDM diagnosis in the first trimester.ConclusionWe found that although the rates of GDM more than doubled with the One-step strategy, the One-step approach was similar to the Two-step approach in terms of maternal and neonatal outcomes. These findings may warn that more caution should be exercised in adopting the One-step method worldwide. Future research is needed to assess the long-term harm and benefits of those approaches to GDM screening for both mothers and their offspring.Clinical trial registrationhttps://www.irct.ir/trial/518, identifier (IRCT138707081281N1).

BackgroundDetermining a thyroid hormone cutoff value in pregnancy is challenging issue and several approaches have been introduced to optimize a utility function. We aimed to estimate the cutoff value of TSH using Bayesian method for prediction of preterm-birth.MethodsThis study was a secondary-analysis of the population-based data collected prospectively within the framework of the Tehran Thyroid and Pregnancy Study. A total of 1,538 pregnant women attending prenatal clinics.ResultsUsing Bayesian method resulted a TSH-cutoff of (3.97mIU/L,95%CI:3.95-4.00) for distinguishing pregnant women at risk of preterm-birth. The cutoff was associated with acceptable positive predictive and negative predictive values (0.84,95% CI:0.80-0.88) and 0.92 (95%CI: 0.91-0.94), respectively). In women who were negative for thyroid peroxides antibody (TPOAb) with sufficient urinary iodine concentration (UIC), the TSH cutoff of 3.92 mIU/L(95%CI:3.70-4) had the highest predictive value; whereas in TPOAb positive women with insufficient UIC, the cutoff of 4.0 mIU/L(95%:CI 3.94-4) could better predict preterm birth. Cutoffs estimated in this study are close to the revised TSH value of 4.0mIU/L which is currently recommended by the American Thyroid Association.ConclusionRegardless of TPOAb status or iodine insufficiency, risk of preterm labor is increased in pregnant women with TSH value of > 3.92 mIU/L; these women may benefit from Levothyroxine (LT4) therapy for preventing preterm birth.

It is currently debated whether vitamin D requirements during pregnancy differ from those during non-gravid states. In current analyses, we aimed to determine the best model for the association between PTH and serum 25-hydroxyvitamin D (25(OH)D) and the threshold for circulating 25(OH)D at which serum parathyroid hormone (PTH) is suppressed. This multicenter prospective cross-sectional study was conducted on 227 Iranian pregnant women aged 15–45 years in their third trimester of pregnancy. The locally weighted smoothing scatter plot (LOWESS) was used to determine the curvilinear shape of the 25(OH)D/PTH relationship. Linear and non-linear methods were employed to determine the best fit and cut-point for serum 25(OH)D concentration. The median serum 25(OH)D and corresponding serum PTH concentration were 17⋅26 (13⋅44–23⋅08) ng/ml and 19⋅46 (15⋅08–25⋅04) pg/ml in our study population, respectively. The LOWESS curve suggested a non-linear and monotonic with a negative slope relation between PTH (pg/ml) and serum 25(OH)D (ng/ml). The optimal model for the association between PTH and serum 25(OH)D was a one-term fractional polynomial (FP1) (AIC = 1640⋅463). The FP1 analysis identified the 25(OH)D threshold of 12⋅48 ng/ml at which serum PTH rapidly rose. The expected degree of PTH stimulation seems to have a linear trend as 25(OH)D falls below 40 ng/ml. 25(OH)D (ng/ml) and PTH (pg/ml) had a non-linear and monotonic relationship with a negative slope. Our data suggest that a 25(OH)D threshold of 12⋅48 ng/ml is sufficient for parathyroid hormone suppression, which could be used to screen for deficient individuals.

Background: Previous studies have shown that spiritual experience may reduce cardiovascular disease (CVDs). However, little is known about the relationship between spiritual health and the gender-specific risk of CVDs in communities with different cultures. Methods: A total of 3249 individuals (53.7% female, 75.0% middle-aged) participated in the Tehran Lipid and Glucose Study (TLGS) from 2015 to 2017 were included. Based on the ACC/AHA pooled cohort equation, CVD risk over ten years was examined. Spiritual health was measured using a developed tool for measuring spiritual health in Muslim populations (SHIMA-48). Linear regression models were used to assess the association between spiritual health and ACC/AHA risk scores. The natural logarithm scale was calculated to consider the normal distribution hypothesis of the regression model. Results: The current results suggest a slight but significant increase in the mean of spiritual health in women compared to men in both cognitive/emotional and behavioral dimensions (P < 0.001). In both sexes, a higher prevalence of smoking was observed in participants with lower levels of spiritual health (P < 0.004). In men, compared to those with a low level of spiritual health (the first tertile), the logarithm of the ACC-AHA risk score was reduced by 0.11 (P = 0.004) and 0.18 (P < 0.001) for those in the second and third tertiles of spiritual health, respectively. This result may be attributed to higher cigarette smoking among the latter group. Similar results were not observed in women. Conclusions: Current results indicate a gender-specific association between spiritual health and cardiovascular disease risk. Our findings imply that promoting spiritual health can be considered an effective strategy in future preventive interventions, primarily by controlling the desire to smoke in men.

Abstract 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/m2, 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

Abstract The effect of live birth/parity number on incident hypertension was investigated among Iranian parous women aged 30–70 years. The study population included 2188 normotensive women who were enrolled in 1999–2001. They were followed for incident hypertension (based on JNC 7 report) by 3‐year intervals up to April 2018. Multivariable Cox proportional hazard models, adjusted for a wide set of potential hypertension risk factors, reproductive factors, and pregnancy complications, were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the number of parity/live birth(s) for incident hypertension. Additionally, as a sensitivity analysis, age‐scale Cox regression was also done. During a median follow‐up of 13.5 years, 935 incident hypertension have occurred. Compared to those with two live births, the participants who had 3 and ≥4 live births were at higher risk of hypertension development by the HRs of 1.25 [95% CI: 1.02–1.55] and 1.39 [1.12–1.72], respectively, in the full‐adjusted model. Moreover, each additional live birth increased the risk of hypertension by a HR of 1.06 [95%CI: 1.02–1.11]. Results of parity number were also similar. Considering age as time scale also did not change the results generally. The authors found a significant interaction between live birth/parity number and age groups; the adverse effect of higher live birth/parity numbers on hypertension development was mainly found among those aged

Abstract Background The prevalence of obesity among children and adolescences have been increased, which can consequently increase the prevalence of metabolic and cardiovascular diseases later in life. The objective of this study is to compare the ability of different childhood body mass index cut-offs in prediction of carotid intima media thickness (CIMT) as an indicator of subclinical atherosclerosis. Methods Participants were categorized into normal weight, overweight and obesity group, based on world health organization (WHO), center for disease control and prevention (CDC), international obesity task force (IOTF) and local IOTF cut-offs. After 18 years of follow up CIMT was measured. Akaike’s information criterion and relative efficiency were measured in order to compare regression models on the role of obesity on CIMT. Results In this prospective cohort study, 1295 subjects aged 3 to 18 years old were enrolled. The overall prevalence of overweight was 15.4, 11.5, 16.3 and 14.1 along with obesity prevalence of 6.6, 8.5, 7.7 and 5.0% based on WHO, CDC, local IOTF and international IOTF criteria, respectively. CIMT was higher in obese compare to normal groups across all classification criteria. After regression analysis, international IOTF was the best to predict adulthood CIMT, followed by local IOTF and WHO. CDC had the least discriminatory ability. Conclusion Due to the results of this study, IOTF could be a better tool in national and international surveillances of children in order to define overweight and obesity, which can help us to intervene more effectively in reducing the burden of cardiovascular diseases.

Abstract 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 R2 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, R2 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.

Abstract 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.

Abstract Background People with prediabetes can postpone or even reverse progression to type 2 diabetes (T2D) by making dietary changes. This study aimed to examine the association of changes in consumption of total and specific types of dairy products with the subsequent risk of incident T2D among individuals with prediabetes. Method This cohort study included 639 individuals (50% female, mean age 47.3 years) of the Tehran Lipid and Glucose Study (TLGS) who had prediabetes at baseline. We assessed 3-year changes in the consumption of dairy products using a food frequency questionnaire. Using multivariable logistic regression, odds ratios (OR) and 95% confidence intervals (CI) were calculated for the association of changes in intake of total and subtypes of dairy products during a 3-year interval with the risk of incident T2D in the subsequent 3 years. Results After almost 9 years of follow-up, the incidence of T2D was 25.2%. Compared with individuals whose intake remained relatively stable over 3 years, those who decreased consumption of total dairy (> 0.5 servings/day) had a higher T2D risk (OR = 1.56; 95% CI: 1.02 to 2.41). Increasing low-fat dairy consumption by 0.50 serving/d was associated with a lower risk of T2D (OR = 0.56; 95% CI: 0.35 to 0.90) compared with stable consumption. Those who increased consumption of low-fat milk (OR = 0.59; 95% CI: 0.37 to 0.92) and low-fat yogurt (OR = 0.55; 95% CI: 0.33 to 0.93) had a lower risk of T2D than those who were relatively stable in their consumption. Replacing low-fat milk and yogurt with regular cheese was associated with 66 and 47% higher risk of T2D, respectively. Conclusion In individuals with prediabetes, increasing consumption of low-fat dairy, low-fat milk, and low-fat yogurt had reduced risk of subsequent T2D. These data suggest a role of low-fat dairy products in the prevention of T2D among prediabetes patients.

Abstract Background Childbearing may increase the future risk of developing type 2 diabetes mellitus (T2DM) in mothers. However, the issue is not clear completely and not investigated in the Middle East, a region with a high burden of T2DM. In the current study, we examined the association of parity/live birth number with incident T2DM among Iranian women. Methods The study population included 2552 women aged 30–65 years recruited in 1999–2001 and were followed for incident T2DM by 3-year intervals. Multivariable Cox proportional hazard models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the parity/live birth number for incident T2DM. Parity number was defined as the number of live childbirth (number of live birth) plus the number of stillbirth (defined as birth of an infant that died after the 20th week of pregnancy in the uterus). Results During a median follow-up of 15.4 years, 557 incident T2DM cases have occurred. After adjustment for potential T2DM risk factors and reproductive factors, each additional parity caused a 9% higher risk for incident T2DM. Moreover, compared to women with one parity, those with 3 and ≥ 4 parity had HRs of 1.73 [95% CI: 1.06–2.83] and 2.23 [1.36–3.65], respectively. After further adjustment for body mass index (BMI) and waist circumference, although the HRs were attenuated prominently, parity ≥ 4 was associated with significantly higher risk (HR: 1.72 [1.05–2.83]); even after further adjustment for triglycerides (TG)/ high-density lipoprotein cholesterol (HDL-C), the risk remained marginally significant (HR: 1.64 [1.00–2.70; P value: 0.051]). For the number of live birth, the results were also similar. Moreover, in a sensitivity analysis, when we considered BMI change during follow-up as another covariate, generally, the effect sizes did not change; the trend of HRs across categories of parity number remained marginally significant (P value: 0.064). Conclusions During a long-term follow-up, after adjustment for potential T2DM risk factors, reproductive factors, obesity indices, and TG/HDL-C (insulin resistance surrogate), we demonstrated that higher parity/live birth numbers could be associated with increased risk of T2DM development among Iranian women. Moreover, even after further adjustment for BMI change, the suggestive higher risk was still found.

Abstract Background The association between dietary fats and the risk of cardiovascular disease (CVD) is under debate. We aimed to determine the potential effects of dietary saturated fats (SFA), mono-unsaturated (MUFA) and poly-unsaturated (PUFA) fatty acids on the occurrence of CVD in an adult Asian population. Methods This study was conducted within the framework of the Tehran Lipid and Glucose Study on 2809 CVD-free adults, aged ≥ 19 years. Dietary intakes of fats were estimated using a validated 168-items semi-quantitative food frequency questionnaire, at baseline. Adjusted hazard ratios and 95% confidence intervals of CVD were calculated in tertile categories of dietary fats. The risk of CVD was estimated with multivariable Cox regression for the substitution of total fat or SFA with other macronutrients. Results During 10.6 years of follow up, the incidence rate of CVD events was 7.1%. Mean (± SD) age of the participants was 39 (± 14) years and 43.9% were men. Total fat, animal and plant sources of fats were not associated with risk of CVD events. No significant associations were found between total SFA, lauric acid, myristic acid, stearic acid, palmitic acid as well as MUFA and PUFA and CVD incidence. Substitutions of total fats or SFA with other macronutrients were not associated with CVD risk. Conclusions In this study, no significant associations were found between dietary fats and CVD risk. Considering the emerging body of literature that suggests no association between fats and CVD risk, reconsideration of dietary recommendations regarding low fat diets to prevent CVD, seems to be essential.