The effect of family structure on the still-missing heritability and genomic prediction accuracy of type 2 diabetes.

This study aims to assess the effect of familial structures on the still-missing heritability estimate and prediction accuracy of Type 2 Diabetes (T2D) using pedigree estimated risk values (ERV) and genomic ERV. We used 11,818 individuals (T2D cases: 2,210) with genotype (649,932 SNPs) and pedigree information from the ongoing periodic cohort study of the Iranian population project. We considered three different familial structure scenarios, including (i) all families, (ii) all families with ≥ 1 generation, and (iii) families with ≥ 1 generation in which both case and control individuals are presented. Comprehensive simulation strategies were implemented to quantify the difference between estimates of [Formula: see text] and [Formula: see text]. A proportion of still-missing heritability in T2D could be explained by overestimation of pedigree-based heritability due to the presence of families with individuals having only one of the two disease statuses. Our research findings underscore the significance of including families with only case/control individuals in cohort studies. The presence of such family structures (as observed in scenarios i and ii) contributes to a more accurate estimation of disease heritability, addressing the underestimation that was previously overlooked in prior research. However, when predicting disease risk, the absence of these families (as seen in scenario iii) can yield the highest prediction accuracy and the strongest correlation with Polygenic Risk Scores. Our findings represent the first evidence of the important contribution of familial structure for heritability estimations and genomic prediction studies in T2D.

Weight change and risk of incident type 2 diabetes: short, medium and long-term follow-up in tehran lipid and glucose study.

BACKGROUND: Despite the high burden of obesity and Type 2 diabetes (T2DM) in the Middle East/West Asia region, the effect of weight change on the development of T2DM is poorly addressed. Therefore, we aimed to assess the impact of 3-year body weight change on incident of T2DM over 3-, 6-, and 9-year periods among Iranian adults. METHODS: A total of 6930 participants (men = 2567) aged ≥ 20 years free of T2DM or cancer at baseline were included. Weight measurements were taken at baseline (2002-2005) and approximately 3 years later. Participants were categorized based on their weight change ratio into ≥ 5% loss, stable (± 5%), and ≥ 5% gain. Generalized estimating equations (GEE), adjusted with age, sex, education levels, baseline measurements of fasting plasma glucose, weight, waist circumference, triglycerides to high-density lipoprotein cholesterol ratio, family history of diabetes, current smoker, hypertension, and prevalent cardiovascular disease were applied to estimate the Odds ratios (ORs) and 95% confidence intervals (CIs) of weight change categories for incident T2DM, considering stable weight as a reference. RESULTS: During median follow-ups of 3-, 6-, and 9-year, 295, 505, and 748 cases of T2DM occurred, respectively. Weight gain of ≥ 5%, as compared to stable weight group (± 5%), was associated with increased T2DM risk, with ORs of 1.58 (95% CI 1.16-2.14), 1.76 (1.41-2.20), and 1.70 (1.40-2.05) for the 3-, 6-, and 9-year follow-ups, respectively, in multivariable analysis; corresponding values for weight loss ≥ 5% were 0.48 (0.29-0.80), 0.57 (0.40-0.81), and 0.51 (0.38-0.68), respectively. This association persisted even after adjusting for attained weight. Subgroup analysis showed consistent associations across age, gender, and body mass index categories. CONCLUSION: Weight gain and loss of ≥ 5% were associated with increased and decreased risks of incident T2DM, respectively, regardless of attained weight. This association was consistent over various follow-up durations among the Iranian population as recommended by guidelines.

The association between index-year, average, and variability of the triglyceride-glucose index with health outcomes: more than a decade of follow-up in Tehran lipid and glucose study.

BACKGROUND: The association between baseline triglyceride glucose index (TyG index) and incident non-communicable diseases, mainly in Asian populations, has been reported. In the current study, we aimed to evaluate the association between index-year, average, and visit-to-visit variability (VVV) of the TyG index with incident type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease (CVD), and all-cause mortality among the Iranian population. METHODS: The study population included 5220 participants (2195 men) aged ≥ 30 years. TyG index was calculated as Ln (fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2). Average values of the TyG index and also VVV (assessed by the standard deviation (SD) and variability independent of mean) were derived during the exposure period from 2002 to 2011 (index-year). Multivariable Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the TyG index for incident different health outcomes. RESULTS: During more than 6 years of follow-up after the index year, 290, 560, 361, and 280 events of T2DM, hypertension, CVD, and all-cause mortality occurred. 1-SD increase in the TyG index values at the index-year was independently associated with the incident T2DM [HR (95% CI) 2.50 (2.13-2.93)]; the corresponding values for the average of TyG index were 2.37 (2.03-2.76), 1.12 (0.99-1.26, pvalue = 0.05), 1.18 (1.01-1.36), and 1.29 (1.08-1.53) for incident T2DM, hypertension, CVD, and all-cause mortality, respectively. Compared to the first tertile, tertile 3 of VVV of the TyG index was independently associated with incident hypertension [1.33 (1.07-1.64), Ptrend <0.01]. Likewise, a 1-SD increase in VVV of the TyG index was associated with an 11% excess risk of incident hypertension [1.11 (1.02-1.21)]. However, no association was found between the VVV of the TyG index and other outcomes. Moreover, the impact of index-year and average values of the TyG index was more prominent among women regarding incident CVD (P for interactions < 0.05). CONCLUSION: Although the higher TyG index at index-year and its VVV were only associated with the incident T2DM and hypertension, respectively, its average value was capable of capturing the risk for all of the health outcomes.

Association between dietary antioxidants intake and the risk of type 2 diabetes mellitus in a prospective cohort study: Tehran Lipid and Glucose Study.

The present prospective cohort study aimed to determine whether dietary antioxidants were associated with incident type 2 diabetes mellitus (T2DM). Another objective was to find out whether such associations could be modified by the BMI status. A total of 2188 Tehranian adults aged 21-84 years, free of T2DM with the validated FFQ, was entered in the study. Multivariable Cox proportional hazards models adjusting for confounders were used to assess the association between dietary antioxidants and incident T2DM in total population, as well as in subjects with various BMI statuses. During 8·9 (8·1-9·6) years of follow-up, dietary vitamin E significantly decreased the incident T2DM, after adjustment for confounders. However, other dietary antioxidants were not shown to be significantly associated with incident T2DM. The interaction between dietary vitamin E, Mg and BMI status was found to influence the risk of T2DM (Pfor interaction < 0·05). After stratification of subjects based on BMI status, it was found that vitamin E and Mg decreased the risk of T2DM only among normal-weight individual. Also, an inverse association was found among dietary vitamin C, dietary Zn and the risk of T2DM in individuals with normal weight but not in overweight and obese individuals; however, the interaction test tended to be significant for these dietary variables. Dietary antioxidants including vitamin E, vitamin C, Zn and Mg when accompanied by healthy weight, may bring benefits to the prevention of T2DM.

Association between anti-mullerian hormone and metabolic syndrome: insights from a prospective community-based study.

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

Socio-behavioral determinants of health-related quality of life among patients with type 2 diabetes: comparison between 2015 and 2018.

INTRODUCTION: Type 2 diabetes (T2D) is a common chronic disease that significantly affects an individual's overall health and well-being. The aim of this study is to investigate the factors that influence the health-related quality of life (HRQoL) of patients with T2D. METHODS: This study conducted using data from 6th phase (2015-2017) and 7th phase (2018-2022) of the Tehran Lipid and Glucose Study (TLGS). Data were collected through a combination of interviews, physical examinations, and laboratory tests. Quality of life questionnaire (SF-12) that consists of 12 questions was used to assess physical and mental health functioning. The generalized estimating equation model was used to assess the association between socio-behavioral factors and changes in HRQoL. RESULTS: The study included 498 patients with T2D. The changes in HRQoL in patients with T2D followed a sex-specific pattern. Analysis of the physical component score (PCS) and the mental component score (MCS) showed a non-significant change in the total score during the three-year longitudinal study. However, the role physical (RP) of the PCS and the social functioning (SF) of the MCS showed a statistically significant change during this period. In addition, sex, body mass index (BMI), and having cardiovascular disease (CVD) and chronic kidney disease (CKD) showed a significant association with RP changes, and only job status showed a significant association with SF changes. CONCLUSIONS: By recognizing the sex-specific patterns in HRQoL changes and understanding the multifaceted nature of factors such as BMI, CVD and CKD, healthcare professionals can develop targeted interventions that go beyond traditional diabetes management.

Macronutrients quality indices and risk of metabolic syndrome and its components in Iranian adults.

BACKGROUND/AIM: Evidence from recent studies suggested that the quality of dietary macronutrients can play a possible role in predicting the risk of metabolic disorders. In the current study, we aimed to assess the association of carbohydrate quality index (CQI) and protein score with the risk of metabolic syndrome (MetS) in Iranian adults. METHODS: This prospective study was conducted within the framework of the Tehran Lipid and Glucose Study on 1738 individuals aged between 40 and 70 years old, who were followed up for a mean of 6.1 years. A food frequency questionnaire was used to determine CQI and protein scores. The multivariable adjusted Cox regression model was used to calculate the hazard ratio (HR) of MetS across quartiles of protein score and CQI, and its components. RESULTS: The mean ± standard deviation (SD) age and body mass index of the study population (42.5% men) were 49.3 ± 7.5 years and 27.0 ± 4.0 kg/m2, respectively. Mean ± SD scores of CQI and protein for all participants were 12.6 ± 2.4 and 10.3 ± 3.5, respectively. During the study follow-up, 834(48.0%) new cases of MetS were ascertained. In the multivariable-adjusted model, the risk of MetS was decreased across quartiles of CQI (HR = 0.83;95%CI:0.69-1.00, Ptrend=0.025) and protein score (HR = 0.75; 95% CI:0.60-0.94, Ptrend=0.041). Also, Of CQI components, the whole grain/total grains ratio showed a significant inverse association with the risk of MetS (HR = 0.75;95%CI:0.60-0.94, Ptrend=0.012). CONCLUSION: Our findings revealed that a dietary pattern with higher CQI and protein score may be related to a reduced risk of MetS in adults.

From adolescence to adulthood: Mediterranean diet adherence and cardiometabolic health in a prospective cohort study.

BACKGROUND AND AIMS: Recent investigations suggest that specific dietary patterns during adolescence may predict cardiometabolic complications later in life. In this study, we aimed to examine the association between Mediterranean diet score (MDS) during adolescence and cardiometabolic outcomes when participants reached adulthood. METHODS AND RESULTS: This cohort study was conducted on 668 subjects, aged 10-19 years, in framework of the Tehran Lipid and Glucose Study. The MDS was determined based on eight components using a validated food-frequency questionnaire. Anthropometric measurements, fasting blood glucose (FBG), and lipid profile data were measured both at baseline and after a 6.8 ± 2.9-year follow-up. Using multivariable linear regression, we explored the association between MDS and changes in cardiometabolic risk factors. Moreover, multivariable-adjusted cox proportional hazard regression was used to estimate hazard ratios (HR) and 95 % confidence intervals (CIs) for cardiometabolic complications across MDS tertiles. The mean ± SD age of participants (43.5 % men) was 15.8 ± 2.47 years. The mean ± SD of MDS was 4.03 ± 1.56, with a median of 4.00 among all participants. Higher MDS was inversely associated with 6.8-year changes in waist circumference (WC), FBG, total cholesterol (TC), and high-density lipoprotein-cholesterol (Ptrend<0.05). Based on the HR analysis, after controlling for potential confounders, individuals in the highest tertile of MDS had a significantly lower risk of high-TC(HR = 0.36,95%CI:0.18-0.74,Ptrend = 0.004) compared to those in the lowest tertile. However, no significant association was observed between MDS and other cardiometabolic risk factors. CONCLUSIONS: Greater adolescent adherence to a Mediterranean-type diet was associated with favorable cardiometabolic factors in adulthood, including improving the levels of WC, FBG, TC, as well as reduced risk of high-TC.

The association between parental cardiovascular health status and the risk of obesity in their offspring: Tehran Lipid and Glucose Study.

BACKGROUND AND AIMS: Little is known about the association of parental cardiovascular risk factors with the risk of obesity in offspring. We aimed to investigate whether parental ideal cardiovascular health (ICVH) status was associated with the risk of general and central obesity in their young/adult offspring. METHODS AND RESULTS: Of individuals who participated in the 2012-15 phase of the Tehran Lipid and Glucose Study, 2395 pairs of parent-unmarried offspring aged ≥6 years were selected in this cross-sectional study. General and central obesity were defined based on Iranian BMI percentile reference data for offspring aged ≤18 years. For subjects aged ≥19 years, central obesity was defined based on the introduced cut-off points for Iranian adults. We employed the American Heart Association's 2020 impact goal criteria of ICVH. The mean ± SD age of fathers and mothers were respectively 55.4 ± 9.79 and 48.4 ± 9.88. About 55% of offspring were older than 19 years. Higher adherence to ICVH score in mothers was associated with lower risk of overweight/obesity in female offspring (OR for Q1-Q4: 1, 0.56, 0.57, 0.37, P < 0.05 for all quartiles). Among ICVH components, only ideal BMI status in fathers was observed to be associated with a lower risk of overweight/obesity in their male offspring. The risk of abdominal obesity decreased in female offspring with increasing total ICVH score in mothers. CONCLUSION: Higher adherence of parents to ICVH and its components was positively associated with a lower risk of general and abdominal obesity in their offspring. Our findings demonstrate that maternal-offspring relationship was stronger than paternal-offspring association.

Causal effect of serum 25 hydroxyvitamin D concentration on cardioembolic stroke: Evidence from two-sample Mendelian randomization.

BACKGROUND AND AIMS: The putative association between serum 25-hydroxyvitamin D concentration [25(OH)D] and the risk of cardioembolic stroke (CES) has been examined in observational studies, which indicate controversial findings. We performed Mendelian randomization (MR) analysis to determine the causal relationship of serum 25(OH)D with the risk of CES. METHODS AND RESULTS: The summary statistics dataset on the genetic variants related to 25(OH)D was used from the published GWAS of European descent participants in the UK Biobank, including 417,580 subjects, yielding 143 independent loci in 112 1-Mb regions. GWAS summary data of CES was obtained from GIGASTROKE Consortium, which included European individuals (10,804 cases, 1,234,808 controls). Our results unveiled a causal relationship between 25(OH)D and CES using IVW [OR = 0.82, 95% CI: 0.67-0.98, p = 0.037]. Horizontal pleiotropy was not seen [MR-Egger intercept = 0.001; p = 0.792], suggesting an absence of horizontal pleiotropy. Cochrane's Q [Q = 78.71, p-value = 0.924], Rucker's Q [Q = 78.64, p-value = 0.913], and I2 = 0.0% (95% CI: 0.0%, 24.6%) statistic suggested no heterogeneity. This result remained consistent using different MR methods and sensitivity analyses, including Maximum likelihood [OR = 0.82, 95%CI: 0.67-0.98, p-value = 0.036], Constrained maximum likelihood [OR = 0.76, 95%CI: 0.64-0.90, p-value = 0.002], Debiased inverse-variance weighted [OR = 0.82, 95%CI: 0.68-0.99, p-value = 0.002], MR-PRESSO [OR = 0.82, 95%CI 0.77-0.87, p-value = 0.022], RAPS [OR = 0.82, 95%CI 0.67-0.98, p-value = 0.038], MR-Lasso [OR = 0.82, 95%CI 0.68-0.99, p-value = 0.037]. CONCLUSION: Our MR analysis provides suggestive evidence that increased 25(OH)D levels may play a protective role in the development of cardioembolic stroke. Determining the role of 25(OH)D in stroke subtypes has important clinical and public health implications.

Quality and quantity of macronutrients, and their joint associations with the incidence of type 2 diabetes over a nine-year follow-up.

BACKGROUND: The association between macronutrient consumption and the risk of type 2 diabetes (T2D) remains equivocal. Here, we investigated whether the quantity and quality of macronutrient intake are associated with T2D incidence in a West Asian population. METHODS: T2D-free adults (n = 2457, mean age 38.5 ± 13.6 years, 54.2% women) who participated in the third examination cycle (2005-2008) of the Tehran Lipid and Glucose Study were followed for a median of 8.6 years. We estimated the macronutrient quality index (MQI), its individual sub-indices (carbohydrate quality index (CQI), fat quality index (FQI), and healthy plate protein quality index (HPPQI)), as well as the macronutrient quantity. The risk of T2D in relation to macronutrient quantity, quality, and their combined effects was examined using Cox proportional hazard models adjusted for known risk factors for T2D. RESULTS: During the study follow-up, 257 incident cases of T2D were documented. Individuals in the highest tertiles of MQI and CQI had a 27% (HR = 0.73, 95% CI = 0.54, 0.98) and 29% (HR = 0.71, 95% CI = 0.51-0.99) lower T2D risk than those in the lowest tertiles. The T2D incidence was 35% lower in the middle HPPQI tertile than in the lowest (HR = 0.65, 95% CI = 0.47, 0.89). The multivariable adjusted model showed that individuals in the middle and highest tertiles of carbohydrate intake had 32% (HR = 0.68, 95% CI = 0.49-0.95) and 26% (HR = 0.74, 95% CI = 0.55-1.00) lower risks of T2D than individuals in the lowest tertile. A high-quantity, high-quality carbohydrate diet (≥ 58.5% of energy from carbohydrate with a CQI ≥ 13) and a low-glycemic index (GI), high-fiber diet (GI < 55 and fiber ≥ 25 g/d) were related to a reduced risk of T2D by 34% (HR = 0.66, 95% CI = 0.47, 0.93) and 42% (HR = 0.58, 95% CI = 0.38, 0.90), respectively. CONCLUSION: A diet with a higher carbohydrate quality may be associated with a lower T2D incidence, particularly when the carbohydrate quantity is also high.

To what extent the weight changes impact the risk of hypertension among menopausal women: insights from Tehran lipid and glucose study.

BACKGROUND & AIM: The association between weight change and incident hypertension (HTN) in menopausal women has not been well characterized. This study aimed to determine whether weight changes after menopausal years make a difference in incidents of hypertension. MATERIALS & METHODS: This population-based study was performed using data collected from Tehran Lipid and Glucose Study cohort (1999-2018). Women who had natural and early menopause were followed up every 3 years. Data gathering was performed through the standard protocol of the study. Statistical analysis was performed using multivariable Cox hazard regression analysis. We used the 'survival' package in the R software version 3.6.0 to fit survival models. RESULTS: A total of 487 menopausal women met the inclusion criteria; 62.6% had natural menopause and remained had early menopause. Among the participants, 65.5% experienced HTN. The highest proportion of participants had > 5% weight gain, while the lowest had 3-5% weight gain. Either losing body weight (lost > 5%: HR: 0.44; CI 95%, 0.32, 0.62; p < 0.001), (lost 3-5%; HR: 0.47; CI 95%, 0.26, 0.84; p = 0.01), and weight gain > 5% (HR: 0.69; CI 95%, 0.51, 0.91; p = 0.01), were associated with decreased risk of HTN after adjustment for confounders. In this study, weight loss and gain have a protective impact on the development of HTN in subjects. For incident HTN, age (HR: 1.04 (1.01, 1.08), p = 0.004), fasting blood glucose (HR: 1.01, CI 95%:1.00, 1.01; p < 0.001), body mass index (1.02 (1.00, 1.05), p = 0.03) and smoking (1.70 (1.11, 2.58), p = 0.01) were positively associated with HTN. CONCLUSIONS: Our study indicates the significant association of weight change with hypertension risk in later life among menopausal women.

Impact of adiposity indices changes across the lifespan on risk of diabetes in women: trajectory modeling approach.

AIMS: The impact of life-course different adiposity indices on diabetes mellitus (DM) is poorly understood. We aimed to do trajectory analysis with repeated measurements of adiposity indices in the development of DM among women across the lifespan. METHODS: This study prospectively investigated the 1,681 population of Tehran Lipid and Glucose Study. At baseline, all individuals were free of diabetes. Trajectory analysis was used to identify homogeneous distinct clusters of adiposity indices trajectories and assign individuals to unique clusters. RESULTS: Of the 1681 healthy women, 320 progressed to the DM. Three distinct body mass index (BMI) trajectories and 2 distinct trajectories of other adiposity indices (waist circumstance (WC), conicity index (C-index), and body roundness index (BRI)) were chosen as the best fitting of the latent class growth mixture model. In the adjusted model, total participants [HR (CI 95%): 2.83 (2.05, 3.91); p < 0.001], and menopause [1.35 (1.10, 2.11); p = 0.001] and reproductive-age women [2.93 (1.80, 4.78); p = 0.003] of the high BMI trajectory compared to the ones in the low trajectory of BMI were more likely to develop DM. The high BRI in menopause had a significantly higher risk of DM compared to the low trajectory. In menopause (1.80 (1.26, 2.58)) and reproductive-age women (4.32 (2.49, 7.47)) with high trajectory of C-index, the DM risk decreased after adjustment. CONCLUSIONS: The risk of DM was greater for high BMI, WC, C-index, and BRI trajectories than for lower trajectories. Hence, the development of general, abdominal, and visceral obesity trajectories in the prevention of DM should be considered by clinicians.

Severity of adipose tissue dysfunction is associated with progression of pre-diabetes to type 2 diabetes: the Tehran Lipid and Glucose Study.

BACKGROUND: The association of prediabetes (Pre-DM) regression and progression with visceral adiposity index (VAI) and adipose tissue dysfunction (ATD) remains to be investigated. METHODS: The present cohort study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS) on 1458 Pre-DM cases (aged ≥ 21 years) who were followed for nine years. VAI was estimated based on waist circumference, body mass index, triglycerides, and high-density lipoprotein cholesterol. ATD status (i.e., absent, mild-moderate, and severe) was defined based on the age-stratified cutoff values of VAI. Multinomial logistic regression models with adjustment of potential confounders were used to estimate the chance of Pre-DM regression to normoglycemia or progression to T2D across ATD status. RESULTS: During the study follow-up, 39.0% of the participants developed T2D, and 37.7% returned to normoglycemia. Compared to mild-moderate ATD, Pre-DM subjects with severe ATD had a higher risk of developing T2D by 45% (OR = 1.45, 95% CI = 11.08-1.93). Severe ATD was also associated with a decreased chance of returning to normoglycemia by 26% (OR = 0.74, 95% CI = 0.55-0.99). Participants with severe ATD had significantly higher fasting (overall mean = 111, 95% CI = 109-112 vs. 106, 95% CI = 105-108 mg/dL) and 2h-serum glucose (overall mean = 165, 95% CI = 161-168 vs. 153, 95% CI = 149-156 mg/dL) concentrations over time. CONCLUSION: Severe ATD was associated with an elevated risk of developing T2D and longitudinal poor-glycemic controls in Pre-DM subjects. ATD may be a simple and useful index for detecting subjects at a higher risk of Pre-DM progression to T2D, allowing for timely intervention strategies.

The association between ultra-processed food consumption and health-related quality of life differs across lifestyle and socioeconomic strata.

BACKGROUND: In this prospective study, we aimed to examine the association between ultra-processed foods and health-related quality of life (HRQoL) and to evaluate the effect of lifestyle and socioeconomic factors on this association. METHODS: This study included 1766 adults (aged 18 to 78, 54.3% women), who took part in the Tehran Lipid and Glucose study. The Short-Form 12-Item Health Survey version 2 was used to determine HRQoL, which includes the physical component summary (PCS) and mental component summary (MCS) scores. Ultra-processed food consumption was assessed using a validated semi-quantitative food frequency questionnaire. Lifestyle (physical activity and smoking status) and socioeconomic factors (education level and employment status) were also determined. General linear models (GLM) were applied to estimate the mean (95% confidence interval) for MCS and PCS scores across the ultra-processed foods tertiles. Additionally, the effect of lifestyle and socioeconomic factors on the relationship between ultra-processed foods and HRQoL was examined using GLM. RESULTS: The median consumption of ultra-processed foods was 11.9% (IQR: 8.2 to 16.8) of total energy intake. There was a significant inverse association between ultra-processed foods consumption and PCS, but not MCS, after adjustment for confounding factors. Significant interactions were observed between ultra-processed food consumption, sex, and occupation on PCS score (all P values < 0.001). The interaction test tended to be significant for smoking status, education levels, and physical activity levels. As ultra-processed food consumption increased, the PCS score significantly decreased in women (P = 0.043), low physical active subjects (P = 0.014), smokers (P = 0.015), and lower-educated individuals (P = 0.022). Non-employed individuals with higher ultra-processed food intake showed a decline in their PCS and MCS scores. While there was no significant difference in MCS score among different strata of lifestyle and socioeconomic status across tertiles of ultra-processed foods. CONCLUSIONS: Higher intake of ultra-processed foods was associated with poorer physical health, particularly among women, those with unhealthy lifestyles, and low socioeconomic conditions.

Cigarette smoking and cardiovascular disease incidence and all-cause mortality: the modifying role of diet quality.

BACKGROUND: This study examines the potential long-term joint association between smoking and diet quality as modifiable risk factors concerning cardiovascular diseases (CVDs) incidence and all-cause mortality among current and former smokers. METHODS: The study followed 955 smokers from the third and fourth examinations of the Tehran Lipid and Glucose Study to March 2018. Dietary data was collected using a food frequency questionnaire. Three diet quality indices (DQIs) were computed at baseline: DQI-international (DQI-I), DQI-revised (DQI-R), and Mediterranean-DQI (Med-DQI). Cox proportional hazards regression models were used to determine the HR (95% CI) of the joint association between smoking and diet quality among heavy and light smokers, based on the number of cigarettes per day and pack-years, as well as between current and former smokers based on smoking habits. RESULTS: Over a follow-up period of almost eight years, 94 cases of CVDs (9.80%) and 40 cases of mortality (4.20%) were documented. The lower diet quality based on the Med-DQI was associated with a higher risk of mortality among current smokers (HR:3.45; 95%CI:1.12, 10.57). Light smokers with good diet quality, compared to heavy smokers with poor diet quality, had a lower risk of CVDs incident (HR:0.35; 95%CI: 0.15, 0.83) and all-cause mortality (HR:0.20; 95%CI:0.05, 0.77). Current smokers with good DQI had a lower risk of mortality compared to current smokers with poor DQI (HR:0.26; 95%CI:0.08, 0.80). However, this lower risk was more significant in former smokers with good DQI (HR:0.10; 95%CI:0.02, 0.45). CONCLUSIONS: Light and former smokers had a lower risk of developing CVDs and experiencing mortality. However, when coupled with a high-quality diet, this protective effect is even more pronounced.

The effect of obesity phenotype changes on cardiovascular outcomes in adults older than 40 years in the prospective cohort of the Tehran lipids and glucose study (TLGS): joint model of longitudinal and time-to-event data.

BACKGROUND: Obesity is a worldwide health concern with serious clinical effects, including myocardial infarction (MI), stroke, cardiovascular diseases (CVDs), and all-cause mortality. The present study aimed to assess the association of obesity phenotypes and different CVDs and mortality in males and females by simultaneously considering the longitudinal and survival time data. METHODS: In the Tehran Lipid and Glucose Study (TLGS), participants older than three years were selected by a multi-stage random cluster sampling method and followed for about 19 years. In the current study, individuals aged over 40 years without a medical history of CVD, stroke, MI, and coronary heart disease were included. Exclusions comprised those undergoing treatment for CVD and those with more than 30% missing information or incomplete data. Joint modeling of longitudinal binary outcome and survival time data was applied to assess the dependency and the association between the changes in obesity phenotypes and time to occurrence of CVD, MI, stroke, and CVD mortality. To account for any potential sex-related confounding effect on the association between the obesity phenotypes and CVD outcomes, sex-specific analysis was carried out. The analysis was performed using packages (JMbayes2) of R software (version 4.2.1). RESULTS: Overall, 6350 adults above 40 years were included. In the joint modeling of CVD outcome among males, literates and participants with a family history of diabetes were at lower risk of CVD compared to illiterates and those with no family history of diabetes in the Bayesian Cox model. Current smokers were at higher risk of CVD compared to non-smokers. In a logistic mixed effects model, odds of obesity phenotype was higher among participants with low physical activity, family history of diabetes and older age compared to males with high physical activity, no family history of diabetes and younger age. In females, based on the results of the Bayesian Cox model, participants with family history of diabetes, family history of CVD, abnormal obesity phenotype and past smokers had a higher risk of CVD compared to those with no history of diabetes, CVD and nonsmokers. In the obesity varying model, odds of obesity phenotype was higher among females with history of diabetes and older age compared to those with no history of diabetes and who were younger. There was no significant variable associated with MI among males in the Bayesian Cox model. Odds of obesity phenotype was higher in males with low physical activity compared to those with high physical activity in the obesity varying model, whereas current smokers were at lower odds of obesity phenotype than nonsmokers. In females, risk of MI was higher among those with family history of diabetes compared to those with no history of diabetes in the Bayesian Cox model. In the logistic mixed effects model, a direct and significant association was found between age and obesity phenotype. In males, participants with history of diabetes, abnormal obesity phenotype and older age were at higher risk of stroke in the Bayesian Cox model compared to males with no history of diabetes, normal obesity phenotype and younger persons. In the obesity varying model, odds of obesity phenotype was higher in males with low physical activity, family history of diabetes and older age compared to those with high physical activity, no family history of diabetes and who were younger. Smokers had a lower odds of obesity phenotype than nonsmokers. In females, past smokers and those with family history of diabetes were at higher risk of stroke compared to nonsmokers and females with no history of diabetes in the Bayesian Cox model. In the obesity varying model, females with family history of diabetes and older ages had a higher odds of obesity phenotype compared to those with no family history of diabetes and who were younger. Among males, risk of CVD mortality was lower in past smokers compared to nonsmokers in the survival model. A direct and significant association was found between age and CVD mortality. Odds of obesity phenotype was higher in males with a history of diabetes than in those with no family history of diabetes in the logistic mixed effects model. CONCLUSIONS: It seems that modifications to metabolic disorders may have an impact on the heightened incidence of CVDs. Based on this, males with obesity and any type of metabolic disorder had a higher risk of CVD, stroke and CVD mortality (excluding MI) compared to those with a normal body mass index (BMI) and no metabolic disorders. Females with obesity and any type of metabolic disorder were at higher risk of CVD(, MI and stroke compared to those with a normal BMI and no metabolic disorders suggesting that obesity and metabolic disorders are related. Due to its synergistic effect on high blood pressure, metabolic disorders raise the risk of CVD.

Lack of beneficiary effect of levothyroxine therapy of pregnant women with subclinical hypothyroidism in terms of neurodevelopment of their offspring.

PURPOSE: Despite the beneficial effects of levothyroxine (LT4) therapy on pregnancy outcomes of women with subclinical hypothyroidism (SCH), its impact on the developmental status of offspring remains unclear. We aimed to assess the effects of LT4 therapy on the neurodevelopment of infants of SCH women in the first 3 years of life. METHODS: A follow-up study was conducted on children born to SCH pregnant women who had participated in a single-blind randomized clinical trial (Tehran Thyroid and Pregnancy Study). In this follow-up study, 357 children of SCH mothers were randomly assigned to SCH + LT4 (treated with LT4 after the first prenatal visit and throughout pregnancy) and SCH-LT4 groups. Children born of euthyroid TPOAb-women served as the control group (n = 737). The neurodevelopment status of children was assessed in five domains (communication, gross motor, fine motor, problem-solving, and social-personal domains) using the Ages and Stages Questionnaires (ASQ) at the age of 3 years. RESULTS: Pairwise comparisons of ASQ domains between euthyroid, SCH + LT4, and SCH-LT4 groups show no statistically significant difference between groups in the total score [median 25-75 total score: 265 (240-280); 270 (245-285); and 265 (245-285); P-value = 0.2, respectively]. The reanalyzing data using the TSH cutoff value of 4.0 mIU/L indicated no significant difference between groups in the score of ASQ in each domain or total score with TSH levels < 4.0 mIU/L, however, a statistically significant difference in the median score of the gross motor was observed between those SCH + LT4 with baseline TSH values ≥ 4.0 mIU/L and SCH-LT4 [60 (55-60) vs. 57.5 (50-60); P = 0.01]. CONCLUSIONS: Our study does not support the beneficiary effect of LT4 therapy for SCH pregnant women in terms of the neurological development of their offspring in the first three years of life.

Low-carbohydrate dietary score and the incidence of metabolically unhealthy phenotype based on BMI status: a cohort study.

There is scarce research focusing on the relationship between the low-carbohydrate dietary score and the development of a metabolically unhealthy phenotype. Therefore, this cohort study was designed to assess the association between the low-carbohydrate dietary score and the risk of metabolically unhealthy phenotypes (MUP). This study included 1299 adults with healthy metabolic profiles who were followed for 5.9 years. Results indicated an inverse association between the second tertile of the low-carbohydrate dietary score and the risk of developing metabolically unhealthy obesity (MUO) (HR: 0.76, 95% CI: 0.59-0.98). In addition, we found an inverse association between the healthy low-carbohydrate dietary score and the risk of MUO (HR: 0.77, 95% CI: 0.60-0.99). Our results revealed a nonlinear inverse association between the low-carbohydrate dietary score and the risk of MUP only in subjects with overweight or obesity. This relationship was independent of animal protein and fat intake. Also, we found that a lower intake of unhealthy carbohydrates was associated with a lower risk of MUP only in subjects with overweight or obesity.

Is variety more important than quantity of fruits and vegetables in relation to cardiovascular disease incidence and mortality? Results from a prospective cohort study.

We aimed to prospectively assess the association between variety and quantity of fruits and vegetables (FV) and cardiovascular diseases (CVD) incidence and mortality due to the limited evidence. Our analysis included 2,918 adults with a follow-up period of 29,559 person-years. An inverse association was detected between fruit intake and the risk of incidence and mortality from CVD. We found no association between diversity scores of fruits, vegetables, and FV with CVD risk. Subjects with high quantity-high variety, high quantity-low variety, and low quantity-high variety of fruits, vegetables, or FV exhibited no difference in CVD risk compared to the subjects with low quantity-low variety intake. Increasing the variety of FV was associated with increases in the intake of ß-carotene, lycopene, lutein, vitamin C, selenium, fibre, fat, and protein after adjustment for the quantity and covariates. We detected an inverse association between fruit intake and the incidence and mortality rates of CVD.