Tracking correlations and predictors of plasma glucose in young adulthood: A comprehensive analysis from adolescence to young adulthood in TLGS study.

AIMS: We investigated the tracking correlations between fasting plasma glucose (FPG) in adolescence with both FPG and 2-hour post-load glucose (2 h-PG) in adulthood, and identified the predictors of FPG and 2 h-PG in young adulthood using traditional risk factors during adolescence and adulthood. METHODS: We included 2188 participants (1033 male) from the Tehran lipid and glucose study within the age ranges 11-18 and 19-40 years during 1999-2018. The area under the curve (AUC) was computed using the growth curve models, and predictors were identified by the linear regression model. RESULTS: The partial correlation between AUCs of FPG in adolescence and adulthood was 0.37 (P < 0.001). The correlation between AUCs of FPG in adolescence and 2 h-PG in adulthood was 0.17 (P < 0.001). The AUC of FPG was a significant positive predictor for both FPG and 2 h-PG in young adulthood. Other predictors of adult FPG included sex, as well as BMI and the ratio of triglycerides to HDL-cholesterol during both adolescence and adulthood. CONCLUSIONS: Tracking correlation was observed for FPG, suggesting that monitoring and managing risk factors in adolescence may have implications for future glucose metabolism in young adulthood.

Sex differences in risk factors for coronary heart disease events: a prospective cohort study in Iran.

We investigated sex-specific associations and their differences between major cardiovascular risk factors and the risk of incident coronary heart disease (CHD) and hard CHD (defined as nonfatal myocardial infarction and CHD death). A total of 7518 (3377 men) participants from the Tehran Lipid and Glucose Study were included. Cox models were used to estimate the hazard ratios (HRs) and women-to-men ratios of HRs for CHD events associated with each risk factor. During 20 years of follow-up (1999-2018), 1068 (631 men) and 345 (238 men) new cases of CHD and hard CHD, respectively, were documented. In total population, the incidence rates per 1000 person-years were 9.5 (9.0-10.1) and 2.9 (2.6-3.2) for CHD and hard CHD, respectively. Hypertension, diabetes, pre-diabetes, and a high waist-to-hip ratio (WHR) were associated with a greater HR of hard CHD in women than men; the women-to-men HRs were 2.85 [1.36-5.98], 1.92 [1.11-3.31], 2.04 [1.09-3.80] and 1.42 [1.10-1.82], respectively. Diabetes was associated with a higher HR of CHD in women than men (ratio of HRs 1.49 (1.10-2.01). In conclusion, we found that hypertension, diabetes, pre-diabetes, and high WHR conferred a greater excess risk of CHD events in women than in men, suggesting that Iranian women may require greater attention for the prevention of CHD events.

Cumulative burden and trajectories of body mass index and blood pressure from childhood and carotid intima-media thickness in young adulthood.

There are significant gaps in understanding of the association between levels and rate of change of body mass index (BMI) and blood pressure (BP) at different ages during childhood and carotid intima-media thickness (CIMT) in adulthood. We investigated the association between trajectories of BMI and BP from childhood to adulthood and adult CIMT among Iranian participants in the Tehran Lipid and Glucose Study (TLGS) cohort. A total of 1334 participants (692 men), from the TLGS cohort (1999-2018) with repeated measurements of BMI and BP (2-6 times) from childhood (3-18 years) to young adulthood (20-40 years) were selected. Trajectory parameters included levels and linear slopes of BMI and BP growth curve models, and cumulative burden defined as the area under those curves (AUC). After adjusting for confounders, AUC of BMI and diastolic blood pressure (DBP) were significantly associated with high CIMT in adulthood, with the standardized odds ratios (OR) and 95% confidence interval (95% CI) of 1.35 (1.12-1.62) and 1.27 (1.01-1.60), respectively. Associations between level-independent slopes of BMI and adult CIMT were significantly positive (ORs: 1.27 to 1.26) during childhood ages (3-18 years). Further, levels of BMI (ORs: 1.23 to 1.29) and DBP (ORs: 1.25 to 1.33) during the ages of 13-18 and 11-17 years, respectively, were significantly associated with CIMT in adulthood (all P < 0.05). The cumulative burden of BMI and DBP was associated with CIMT in adulthood. Adolescence is a crucial period for high CIMT, which has implications for early prevention of atherosclerosis.

Association between estimated glomerular filtration rate slope and cardiovascular disease among individuals with and without diabetes: a prospective cohort study.

BACKGROUND: Previous studies have reported an association between a significant decline in estimated glomerular filtration rate (eGFR) over time and an increased risk of cardiovascular disease (CVD). This study aimed to investigate the association between the eGFR slope and CVD among individuals with and without diabetes. METHODS: This prospective cohort study was conducted within the Tehran Lipid and Glucose Study (TLGS) framework. We studied 6919 adults aged 20-70 years, including 985 with diabetes and 5934 without diabetes. The eGFR slope was determined based on repeated measurements of eGFR through linear mixed-effects models. A multivariable Cox proportional hazard model was employed to evaluate the association between eGFR slope, both in continuous and categorical form, and the risk of CVD. RESULTS: The slopes of eGFR exhibited a bell-shaped distribution, with a mean (standard deviation (SD)) of -0.63 (0.13) and - 0.70 (0.14) ml/min per 1.73 m2 per year in individuals with and without diabetes, respectively. During a median follow-up of 8.22 years, following the 9-year eGFR slope ascertainment period, a total of 551 CVD events (195 in patients with diabetes) were observed. Among individuals with diabetes, a steeper decline in eGFR slope was significantly associated with a higher risk of CVD events, even after adjusting for baseline eGFR, demographic factors, and traditional risk factors for CVD; slopes of (-1.05 to -0.74) and (-0.60 to -0.52) were associated with 2.12 and %64 higher risks for CVD, respectively, compared with a slope of (-0.51 to 0.16). Among individuals without diabetes, the annual eGFR slope did not show a significant association with the risk of CVD. CONCLUSION: Monitoring the eGFR slope may serve as a potential predictor of CVD risk in individuals with diabetes.

The impact of general and central obesity for all-cause hospitalization among Iranian adults: a 20 year follow-up-results from the TLGS cohort.

BACKGROUND: Few studies have examined the effect of obesity indices on total number of hospitalizations. We examined the associations between body mass index (BMI) and waist circumference (WC) and rate of all-cause hospitalizations among Iranian adult participated in the Tehran Lipid and Glucose Study cohort. METHODS: This study included 8202 individuals (3727 men) aged ≥ 30 years, who were followed for a median of 18 years. Participants were categorized into three groups according to their baseline BMI: normal weight, overweight and obese. In addition, they were classified according to WC in two categories: normal WC and high WC. Negative Binomial regression model was used to estimate the incidence rate ratios (IRRs) and 95% confidence interval (95% CI) of all-cause hospitalizations in relation to obesity indices. RESULTS: The overall crude rate of all-cause hospitalizations were 77.6 (95% CI, 73.9-81.2) and 76.9 (73.4-80.3) per 1000 person-year in men and women, respectively. The covariate adjusted rate of all-cause hospitalizations was 27% higher in obese men than normal weight men (IRR (95% CI): 1.27 (1.11-1.42)). Among women, overweight and obese individuals had 17% (1.17 (1.03-1.31)) and 40% (1.40 (1.23-1.56)) higher rate of hospitalization compared to normal weight women. Having high WC was associated with 18% (1.18 (1.08-1.29)) and 30% (1.30 (1.18-1.41)) higher rate of all-cause hospitalization in men and women, respectively. CONCLUSIONS: Obesity and high WC were associated with increased hospitalization rates during long-term follow-up. Our findings suggests that successful obesity prevention programs may decrease the number of hospitalizations, particularly, in women.

Lifetime risk of cardiovascular disease stratified by traditional risk factors: Findings from the cohort of Tehran lipid and glucose study.

BACKGROUND: We aimed to estimate the lifetime risk (LTR) of cardiovascular disease (CVD) in the Iranian population, stratified by sex and traditional risk factors including high body mass index (BMI), hypertension, diabetes, smoking, and hypercholesterolemia. METHODS: We included 10222 (4430 men) participants aged ≥20 years without CVD at baseline. LTRs at index ages 20 and 40 years and number of years lived without CVD was estimated. We further assessed the effect of traditional risk factors on the LTR of CVD and the number of years lived without CVD, stratified by sex and index ages. RESULTS: During a median follow-up of 18 years, 1326 participants (774 men) developed CVD and 430 (238 men) died from non-cardiovascular causes. At age 20, the remaining LTR for CVD was 66.7% (95% CI 62.9-70.4) in men and 52.0% (47.6-56.8) in women, with similar LTRs at age 40 for both men and women. The LTRs at both index ages for those with ≥3 risk factors were about 30% and 55% higher in men and women, respectively, than those without any of the five risk factors. At the age of 20, men with ≥3 risk factors lived 24.1 fewer years without CVD compared with men with no risk factors; the corresponding value was 8 years in their female counterparts. CONCLUSIONS: Our findings suggest that both sexes may benefit from effective prevention strategies early in the life course, despite the observed differences between men and women in LTR for CVD and number of years lived without CVD.

Gender-specific effect of outdoor temperature and seasonal variation on blood pressure components: a cross-sectional study on Iranian adults from 2015 to 2018.

Blood pressure (BP) is influenced by both individual and environmental factors such as ambient temperature. However, the gender-stratified and component-specific impact of temperature on BP is not well understood. Herein, we examined the temperature and seasonal effects on four main BP components, namely systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), in both genders. A total of 8990 (3954 men) Tehranian adults during 2015-2018 were included. Linear regression models for analyzing data in three models including unadjusted, age-adjusted, and further adjusted for known sociodemographic and cardiovascular confounders were conducted. Among women, each 10 °C increment was associated with a significant decrease of - 0.48 mmHg (95% confidence interval (CI): - 0.86, - 0.19) and - 0.65 mmHg (- 0.76, - 0.41) in SBP and MAP, respectively. In men, the corresponding value for SBP was - 0.46 (- 0.82, - 0.16) mmHg (P = 0.058). Gender-specific analysis in each season showed that among women, PP increased in autumn and winter with each 10 °C decrease (P < 0.05). The mean increase in SBP (3.4 and 2.06 mmHg in women and men, respectively), DBP (1.66 and 1.19 mmHg), and MAP (2.71 and 1.12 mmHg) was observed during winter compared to summer (all P < 0.05). PP showed seasonality only in women (1.46 mmHg, P-value = 0.003). In both genders, SBP in age > 60 years was more susceptible to variation compared to younger ages. Furthermore, obese women had more SBP changes compared to their non-obese counterparts (all P for interaction < 0.05). In conclusion, there was a sex difference in BP response to the outdoor temperature, with higher vulnerability among women. The reverse relation between temperature and BP occurred particularly among elderly and obese individuals. Careful monitoring of BP in cold seasons, specifically in the mentioned subgroups, could potentially attenuate cardiovascular risks.

The impact of long-term exposure to PM10, SO2, O3, NO2, and CO on incident dysglycemia: a population-based cohort study.

To examine the associations between long-term exposure to five major air pollutants including SO2, PM10, O3, NO2, and CO, and incident dysglycemia, impaired fasting glucose (IFG), and diabetes, separately. A total of 4254 (1720 men) normoglycemic individuals aged 20-69 years at baseline were followed from 2001 to 2018 every 3 years. To measure the long-term hazards of air pollutants for incident dysglycemia, the Weibull proportional hazards models for every 10-unit increment adjusted for diabetes risk factors were fitted. The air pollutants were put in the models in the form of averages of 1-, 2-, and 3-year periods. During a median follow-up of 12.2 years, we observed 1780 dysglycemia events. In contrast to NO2, the increase in SO2, O3, and PM10 levels were significantly associated with a higher risk of dysglycemia and IFG in all time spans excluding PM10 at 2 years. The largest hazard ratios for incident dysglycemia and IFG were attributable to PM10 in 3 years (2.20 (95% CI 1.67, 2.89) and 2.08 (1.55, 2.80), respectively). Moreover, exposure to all the pollutants except NO2 in 1 year (0.89 (0.80, 0.98)) had no significant associations with incident diabetes. There was a signal that younger (< 45 years) and never-smoker individuals were more predispose to dysglycemic effects of air pollution (all P for interactions > 0.03). Our findings suggested that long-term exposure to air pollution increased incident dysglycemia risk, the effect which was mainly attributable to IFG status.

Changes in Fasting plasma glucose status and risk of mortality events in individuals without diabetes over two decades of Follow-up: a pooled cohort analysis.

BACKGROUND: We aimed to assess the gender-specific impact of 3-year changes in fasting plasma glucose (FPG) status on the risk of all-cause, cardiovascular (CV), and cancer mortality in individuals without type 2 diabetes (T2DM) during an 18-year follow-up. METHODS: The study population included 14,378 participants aged 30-60 years (8272 women) from three population-based cohort studies, including Atherosclerosis Risk in Communities, Multi-Ethnic Study of Atherosclerosis, and Tehran Lipid and Glucose Study. Subjects were classified into six categories based on the approximately three-year changes in FPG status: (1) normal FPG (NFG) to NFG (reference category); (2) NFG to impaired fasting glucose (IFG) (i.e., 126 > FPG ≥ 100 mg/dl); (3) NFG to T2DM; (4) IFG to NFG; (5) IFG to IFG; (6) IFG to T2DM. Multivariable stratified Cox regression, adjusting for age, body mass index (BMI), BMI-Change, smoking status, hypertension, and hypercholesterolemia was used to estimate hazard ratios (HRs (95% CI)) for all-cause and cause-specific mortality events. Women-to-men ratios of HRs (RHRs) for each category were also estimated. RESULTS: During follow-up, 2,362 all-cause mortality events were recorded. Among women, all categories of FPG change, excluding IFG-NFG (HR, 95%CI 1.24 (0.98-1.57), p = 0.07), were associated with a higher risk of all-cause mortality compared to the NFG-NFG category. Moreover, women in IFG-T2DM group were at increased risk for CV mortality (2.21 (1.42-3.44)). We also found that women in NFG-IFG (1.52 (1.20-1.91)), NFG-T2DM (2.90 (1.52-5.51)), and IFG-IFG (1.30 (1.02-1.66)) categories had a higher risk for cancer mortality. However, among men, a higher risk of all-cause mortality was found for only two groups of NFG-T2DM (1.78 (1.15-2.74)) and IFG-T2DM (1.34 (1.04-1.72)). Women with IFG-IFG had a 24% higher risk for all-cause mortality events than their men counterparts (RHR; 1.24 (1.01-1.54)). After further adjustment for physical activity, results were in line with the main findings, excluding T2DM up to six years after the measurement period and early mortality events. CONCLUSION: In women, the IFG status, whether as incident, persistent, or converted to T2DM, had a higher risk for mortality events; however, among men, only conversion to T2DM conferred an excess risk of all-cause mortality.

Gender differences in changes in metabolic syndrome status and its components and risk of cardiovascular disease: a longitudinal cohort study.

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

The relationship between glucose intolerance status and risk of hospitalization during two decades of follow-up: Tehran lipid and glucose study.

OBJECTIVE: To assess the relationship between glucose intolerance statuses at baseline defined as normal glucose tolerance (NGT), pre-diabetes, newly diagnosed (NDM) and known diabetes mellitus (KDM) and all-cause hospitalization among Iranian men and women during 20 years of follow-up. RESEARCH DESIGN AND METHODS: This study included 8,014 individuals (3,836 men) ≥30 years from the cohort of Tehran Lipid and Glucose Study. Incidence rate ratios (IRRs) and (95% confidence interval (95% CI) for three groups of pre-diabetes, NDM and KDM was estimated using the Negative Binomial regression model, considering NGT group as reference group. Regression models were adjusted for age, body mass index, hypertension, chronic kidney disease, and cardiovascular disease (CVD). RESULTS: Among men, compared with NGT group, those with pre-diabetes, NDM and KDM had higher incidence rate for hospitalization, with IRRs (95% CI) of 1.08 (0.96-1.20), 1.38 (1.20-1.57) and 1.96 (1.66-2.26), respectively, after adjusting for confounders. The corresponding values were 1.07 (0.96-1.17), 1.40 (1.21-1.59) and 2.07 (1.72-2.42) for women. Men with diabetes, generally had a higher rate of hospitalization for CVD rather than their female counterparts (IRRs: 1.46; 1.17-1.74). In patients with diabetes, the most common causes of hospitalization were macrovascular complications (i.e. coronary heart disease and stroke). Moreover, among the individuals with diabetes, those with poor glycaemic control (fasting plasma glucose (FPG) >10 mmol/l) had 39% higher rate of hospitalization than those with fair glycaemic control (FPG <10 mmol/l) (1.39; 1.12-1.65), adjusted for confounders. CONCLUSION: Pre-diabetes, NDM, and KDM were associated with increased hospitalization rates during long-term follow-up. Interventions such as lifestyle modification or pharmacological therapies aiming to slow down the pre-diabetes and fair control of diabetes might potentially decrease the rate of hospitalization.Key messagesNDM and KDM status both increased rate of all-cause hospitalization.CVD and T2DM complication were the most common cause of hospitalization among patients with diabetes.Hospitalization due to recurrent CHD was significantly higher in men with diabetes than their female counterparts.

Effect of family history of diabetes and obesity status on lifetime risk of type 2 diabetes in the Iranian population.

Background: Data are scarce for the lifetime risk of diabetes in the Middle East and North Africa region countries. We estimated the lifetime risk of type 2 diabetes among Iranian adults at age 20 and 40 years, and their variation by family history of diabetes and body mass index (BMI). Methods: The data from 8435 diabetes-free participants from the Tehran Lipid and Glucose study were used in this analysis. We estimated the lifetime risk of diabetes stratified by sex, and quantified the impact of family history of diabetes and BMI status on the lifetime risks, singly and jointly. Results: At age 20 years, the overall lifetime risk of diabetes was 57.8% (95% CI = 54.0%-61.8%) for men and 61.3% (57.2%-65.4%) for women. Having both family history of diabetes and increased level of BMI, alone, increased the lifetime risk of diabetes in both sexes. Moreover, the simultaneous presence of family history of diabetes and overweigh/obesity increased the lifetime risk of diabetes in both sexes. So that, at age 20 years the lifetime risk in obese men with positive family history of diabetes was about 54% higher, compared to normal weight men without family history of diabetes; the corresponding value for women was 42%. Also, normal weight men without family history of diabetes lived 24 years longer free of diabetes, compared with obese men with family history of diabetes. In women, the corresponding value was 20 years. Conclusion: Our study shows the alarming lifetime risk of diabetes across the strata of BMI, which emphasizes the need for more effective interventions to reduce incidence, particularly, among individuals with positive family history of diabetes.

Sex differences in the association between diabetes and hypertension and the risk of stroke: cohort of the Tehran Lipid and Glucose Study.

BACKGROUND: We assessed the sex differences in the association between blood pressure categories and glucose intolerance status with overall and ischemic stroke among Iranian adults. METHODS: This prospective study was conducted on 5349 individuals (2446 men) aged ≥ 40 years. Cox models were used to estimate adjusted hazard ratios (HRs) and men-to-women ratios of HRs (RHRs) of overall and ischemic stroke for systolic (SBP) and diastolic (DBP) blood pressure, pre-hypertension, hypertension, fasting plasma glucose (FPG), pre-diabetes and type 2 diabetes (T2D). RESULTS: Each 0.55 mmol/L increase in FPG was associated with a higher HR of overall stroke in men than women [RHRs 1.05 (1.01-1.09)]. The associations between each 10 mmHg increase in DBP and stroke events were stronger in men than women, with RHRs of 1.20 (1.00-1.45) and 1.29 (1.04-1.60) for overall and ischemic stroke, respectively. Hypertension was associated with a higher HR of overall [RHRs: 2.41 (1.21-4.8)] and ischemic stroke [2.37 (1.12-5.01)] in men than women. We also found that T2D was associated with higher risks of overall and ischemic stroke in men than women: the RHRs were 2.16 (1.24-3.75) and 1.93 (1.05-3.55) for overall and ischemic stroke, respectively. CONCLUSION: Hypertension and T2D induced higher risk of overall and ischemic stroke in men than women among Iranian population.

Diabetes mellitus risk prediction in the presence of class imbalance using flexible machine learning methods.

BACKGROUND: Early detection and prediction of type two diabetes mellitus incidence by baseline measurements could reduce associated complications in the future. The low incidence rate of diabetes in comparison with non-diabetes makes accurate prediction of minority diabetes class more challenging. METHODS: Deep neural network (DNN), extremely gradient boosting (XGBoost), and random forest (RF) performance is compared in predicting minority diabetes class in Tehran Lipid and Glucose Study (TLGS) cohort data. The impact of changing threshold, cost-sensitive learning, over and under-sampling strategies as solutions to class imbalance have been compared in improving algorithms performance. RESULTS: DNN with the highest accuracy in predicting diabetes, 54.8%, outperformed XGBoost and RF in terms of AUROC, g-mean, and f1-measure in original imbalanced data. Changing threshold based on the maximum of f1-measure improved performance in g-mean, and f1-measure in three algorithms. Repeated edited nearest neighbors (RENN) under-sampling in DNN and cost-sensitive learning in tree-based algorithms were the best solutions to tackle the imbalance issue. RENN increased ROC and Precision-Recall AUCs, g-mean and f1-measure from 0.857, 0.603, 0.713, 0.575 to 0.862, 0.608, 0.773, 0.583, respectively in DNN. Weighing improved g-mean and f1-measure from 0.667, 0.554 to 0.776, 0.588 in XGBoost, and from 0.659, 0.543 to 0.775, 0.566 in RF, respectively. Also, ROC and Precision-Recall AUCs in RF increased from 0.840, 0.578 to 0.846, 0.591, respectively. CONCLUSION: G-mean experienced the most increase by all imbalance solutions. Weighing and changing threshold as efficient strategies, in comparison with resampling methods are faster solutions to handle class imbalance. Among sampling strategies, under-sampling methods had better performance than others.

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

BACKGROUND: This study is the first to evaluate familial aggregation, heritability and inheritance mode of type 2 diabetes (T2D) in Tehran Lipid Glucose Study (TLGS) participants as a representative sample of the Iranian population. METHODS: From the ongoing family-based TLGS cohort, 13,741 individuals at least 20 years of age (mean ± standard deviation, 39.71±16.56) were assessed. After correcting family structures using genomic information from the Tehran Cardiometabolic Genetic Study, 2,594 constituent pedigrees were constructed. Familial aggregation was assessed based on genealogic index testing, familial intraclass correlation and positive family history. Family-based heritability was checked with 2 linear mixed models, including 2 different random components: the kinship matrix and the genomic relationship matrix. The mode of inheritance of T2D was investigated by complex segregation analysis (CSA). RESULTS: Familial aggregation of T2D was significant (p<0.05), and family-based heritability showed a high degree of genetic variation in T2D between individuals at 65% (standard error, 0.034). Within first-degree relatives (parent/offspring and siblings), the likelihood of a parental affect was higher than in siblings (odds ratio, 4.11 vs 1.65). Family history of T2D among first-degree relatives was more noteworthy than for second-degree relatives (odds ratio, 3.84 vs 0.59). CSA revealed that the polygenic model is best to illustrate the mode of inheritance of T2D for TLGS participants. CONCLUSIONS: Our findings demonstrate that the heritability of T2D with polygenic mode in the Iranian population is higher than the global average. We also found that T2D is transmitted equally into siblings, with parental affect the leading risk factor. These data suggest that policymakers should change individual-level to family-level prevention.

Sex Differences in Cumulative Exposure to Metabolic Risk Factors Before Hypertension Onset: The Cohort of the Tehran Lipid and Glucose Study.

Background Previous studies have shown a sex difference in the association between hypertension and cardiovascular disease; however, the precise mechanism remains unclear. Because there are strong associations between metabolic risk factors (MRFs) and hypertension, a sex-specific analysis of MRFs before hypertension onset could offer new insights and expand our understanding of sex differences in cardiovascular disease. We evaluated cumulative exposure to major MRFs and rate of change of those factors, including body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol, triglycerides, and high-density lipoprotein cholesterol among individuals who did and did not develop hypertension at follow-up. Methods and Results We included 5374 participants (2191 men) initially without hypertension with age range of 20-50 years at baseline who participated in the Tehran Lipid and Glucose Study, and had been examined at least 3 times during the study period (1999-2018). In both sexes, the cumulative exposure to all MRFs (except for fasting plasma glucose and high-density lipoprotein cholesterol in men) were higher in those who developed hypertension, compared with those who did not develop hypertension. However, women experienced greater cumulative exposure to major MRFs, compared with their male counterparts. Also, they experienced a faster increase in waist circumference, systolic blood pressure, diastolic blood pressure, and high-density lipoprotein cholesterol than men. Furthermore, rapid increase in systolic blood pressure began earlier in women than men, at the age of 30 years. We also found that those men who developed hypertension experienced unfavorable change in major MRFs during young adulthood (<50 years of age). Conclusions Women exhibited more metabolic disturbances than men before onset of hypertension, which may explain the stronger impact of hypertension for major types of cardiovascular disease in women, compared with men.

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

AIM: To examine whether visit to visit variability (VVV) of fasting plasma glucose (FPG) is associated with incident cardiovascular diseases (CVD) and all-cause mortality in individuals with and without type 2 diabetes (T2D). METHODS: A total of 4756 participants aged ≥30 years entered the study in 2002-2005 and underwent two subsequent examinations in 2005-2008 and 2008-2011. FPG variability measures included standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of mean (VIM). Multivariate Cox proportional hazard models were used to assess the risk of incident CVD and all-cause mortality for each unit increase in different FPG variability measures. RESULTS: During a median follow-up of 18.14 years after baseline recruitment, 492 incident cardiovascular diseases and 338 all-cause mortality were recorded. Among individuals without T2D, the multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD were 1.02 (1.01-1.04), 1.02 (1.01-1.04), 1.01 (1.00-1.02), and 1.01 (1.00-1.01) for SD, CV, ARV, and VIM, respectively (all P-values <0.05). Among individuals with T2D, the corresponding HRs and 95% CIs for all-cause mortality were 1.01 (1.00-1.02), 1.02 (1.01-1.03), 1.01 (1.00-1.02), and 1.01 (1.00-1.01), respectively (all P-values <0.05). CONCLUSION: Long-term (VVV) of FPG is significantly associated with increased risk of CVD among participants without T2D, and all-cause mortality among participants with T2D.

Age and aging effects on blood pressure: 15 years follow-up of Tehran lipid and glucose study.

Age is a known predictor of blood pressure (BP); however, the literature mostly includes cross-sectional investigations. This prospective cohort study aimed to decompose the cross-sectional and longitudinal age effects on BP. The secondary data were obtained from the Tehran lipid and glucose study, which comprised six repeated measurements of participants, with median follow-up of 15.8 (interquartile range of 14.2-16.9) years. The sample is representative of the metropolitan area of Tehran, Iran, containing 7,460 participants aged 20-70. The cross-sectional and longitudinal effects of age (age at baseline and aging, respectively) were fitted in the mixed effects models, taking systolic, diastolic, and pulse BPs as response, adjusting for adiposity, smoking, diabetes, and antihypertensive medication, and stratifying for sex and 10-year age-groups. The mean age at baseline was 41.3 (SD = 12.9) years, and 41.7% of the participants were male. Age at baseline and aging were directly associated with BP, aging owned the weaker effect, and the largest distinction were for systolic blood pressure of men aged 40-49 years (0.75 vs 0.10, p-value < .001). Moreover, the aging effects on systolic and diastolic BPs were higher in men than women, in the age groups 40-49 and 30-39 years (0.35 vs 0.10 and 0.30 vs 0.07, p-values < .001), respectively. Adjusting for adiposity remarkably declined the impact of aging on BP, among the < 50 years old.

The association of priori and posteriori dietary patterns with the risk of incident hypertension: Tehran Lipid and Glucose Study.

BACKGROUND: The aim of this study was to investigate the association of dietary patterns with incident hypertension. MATERIALS/METHODS: This prospective study was conducted on 4793 individuals of Tehran lipid and glucose study participants, aged ≥ 18 years who were followed for a median of 6.3 years from 2008-2011 to 2016-2018. A valid and reliable semi-quantitative food frequency questionnaire was used to assess usual dietary intakes. Anthropometrics and blood pressure were assessed at baseline and during follow up examinations. Dietary patterns were derived using principal component analysis (PCA). Healthy eating index (HEI) and dietary approach to stop hypertension (DASH) score were measured based on dietary recommendations. Time-dependent Cox models adjusting for confounders were used to examine the association between dietary patterns and the risk of hypertension. RESULTS: During follow-up, a total of 727 incident cases of hypertension were identified. The mean ± SD age at baseline was 40.3 ± 13.5 and 37.9 ± 12.1 years in men and women, respectively. Two dietary patterns (the healthy and unhealthy) were extracted by PCA. Compared with participants in the first quartile, a 23% (HR: 1.23; 95%CI 1.00-1.53; P trend: 0.056) increased risk of hypertension was found in the fourth quartile of HEI score. This association was disappeared after further adjustment for confounders. Increasing DASH score, the healthy and unhealthy dietary pattern were not associated with risk of hypertension. CONCLUSION: Our findings showed that higher adherences to the posteriori- and priori-dietary patterns were not associated with risk of hypertension in this population.