Examining the clinical and genetic spectrum of maturity-onset diabetes of the young (MODY) in Iran.

Maturity-onset diabetes of the young (MODY) is an uncommon monogenic type of diabetes mellitus. Detecting genetic variants for MODY is a necessity for precise diagnosis and treatment. The majority of MODY genetic predisposition has been documented in European populations and a lack of information is present in Iranians which leads to misdiagnosis as a consequence of defects in unknown variants. In this study, using genetic variant information of 20,002 participants from the family-based TCGS (Tehran Cardiometabolic Genetic Study) cohort, we evaluated the genetic spectrum of MODY in Iran. We concentrated on previously discovered MODY-causing genes. Genetic variants were evaluated for their pathogenicity. We discovered 6 variants that were previously reported in the ClinVar as pathogenic/likely pathogenic (P/LP) for MODY in 45 participants from 24 families (INS in 21 cases, GCK in 13, HNF1B in 8, HNF4A, HNF1A, and CEL in 1 case). One potential MODY variant with Uncertain Risk Allele in ClinVar classification was also identified, which showed complete disease penetrance (100%) in four subjects from one family. This is the first family-based study to define the genetic spectrum and estimate the prevalence of MODY in Iran. The discovered variants need to be investigated by additional studies.

Effect of metformin (vs. placebo or sulfonylurea) on all-cause and cardiovascular mortality and incident cardiovascular events in patients with diabetes: an umbrella review of systematic reviews with meta-analysis.

Purpose: The current umbrella review aimed to evaluate the effect of metformin on all-cause mortality (ACM), cardiovascular mortality, and cardiovascular disease (CVD) incidence in DM patients. Methods: PubMed, Scopus, Cochrane, Google Scholar, and Web of Science databases were searched with special keywords. Related studies were included after screening by two independent investigators based on title and full texts. The AMSTAR2 checklist was used to assess the quality of studies, and Cochran tests were used to assess the heterogeneity between studies. Overall, seventeen systematic reviews and meta-analysis studies were included. The results revealed that the risk of ACM in patients who received metformin was lower than in patients who did not receive metformin. (OR: 0.80, 95% CI:0.744,0.855); also, the risk of CVD mortality in metformin patients was lower than in the other two groups (placebo and other anti-diabetic drugs) (OR: 0.771, 95% CI:0.688,0.853, P:0.001). The risk of CVD in metformin users was also lower than in the other two groups (OR: 0.828, 95% CI:0.781,0.785). Summary: This comprehensive review showed that the risk of ACM, death due to CVD, and incidents of CVD in DM who use metformin was lower than the patients who received a placebo only or other diabetic drugs, which can guide clinicians in medical decision-making. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01309-y.

Association of Anthropometric Indices With Midlife Cardiovascular Risk in Young Individuals Without Obesity and Traditional Risk Factors.

BACKGROUND: The aim of this study was to assess how early-adulthood body mass index (BMI) and waist circumference (WC) relate to long-term cardiovascular structure, function, and prognosis in individuals without obesity and with low cardiovascular risk factor (CVRF) burden. METHODS AND RESULTS: A total of 2024 participants aged 18 to 30 from the CARDIA (Coronary Artery Risk Development in Young Adults) study, without obesity and with low CVRFs defined as the absence of cardiovascular disease (CVD), diabetes, hypertension, current smoking, and dyslipidemia were included. A CVRF-optimal subgroup was also defined, with blood pressure<120/80 mm Hg, fasting glucose <100 mg/dL, total cholesterol <200, low-density lipoprotein cholesterol <130, and women with high-density lipoprotein cholesterol ≥50 mg/dL. Coronary artery calcification, carotid intima-media thickness, left ventricular mass, left ventricular ejection fraction, longitudinal peak systolic strain, and diastolic function were assessed in midlife. Cox regression was used to calculate hazard ratios of BMI and WC for all-cause death and CVD events. Logistic regression was used to estimate odds ratios for subclinical CVD. Over 33.9 years (median follow-up), 5.2% (n=105) died, and 2.6% (n=52) had CVD events. Each 1-SD BMI increase was associated with 27% (95% CI, 1.10-1.47), 24% (1.08-1.43), 42% (1.20-1.68), 28% (1.05-1.57), 51% (1.20-1.90), and 49% (1.10-2.02) higher odds of coronary artery calcification presence, increased carotid intima-media thickness, left ventricular hypertrophy, reduced left ventricular ejection fraction, low longitudinal peak systolic strain, and diastolic dysfunction, respectively, in the CVRF-low group. Generally, similar associations were found for WC and in the CVRF-optimal subgroup. No significant associations between BMI and WC with CVD and death were found. CONCLUSIONS: Elevations in BMI and WC among young low-risk individuals, even within the nonobesity range, are associated with midlife cardiovascular health.

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.

Bibliometric overview of the Tehran Lipid and Glucose Study (TLGS) publications from 2000 to 2022.

Aim: The present study was conducted to analyze the publications of the Tehran Lipid and Glucose Study (TLGS) and assess its scientific productions during the last 23 years. Methods: The required data were retrieved from the Scopus database. The advanced search was chosen, and the search query included terms related to the TLGS. Search and retrieval of data were conducted on August 30, 2022. Bibliometric indicators have been used at three levels in this research including the level of documents, journals, and authors. Also, the knowledge structure of this set was analyzed at the level of social structure and the level of conceptual structure. Data analysis and visualizations was performed using Bibliometrix and VOSviewer software. Results: A total of 870 documents related to the TLGS have been indexed in the Scopus from 2000 to 2022, and 1148 authors have participated in the relevant studies. 66.4% of the TLGS documents were published in journals with Q1 subject area quartiles. There was an annual growth rate of 20% and average citations per document of 16.5. There was a co-authorship per document of 5.6 and an international co-authorship of 8.7%. According to the co-occurrence network for keywords, the most common areas in the TLGS published documents were nutrition, epidemiologic issues, cardiometabolic-related biomarkers, diabetes, hypertension, lifestyle variables and genetic studies. Conclusion: Over the past 23 years, the TLGS has successfully addressed a wide range of inquiries pertaining to cardiometabolic and nutritional issues in Iran. The remarkable achievements of the TLGS act as a catalyst, advocating for the planning and implementation of additional cohort studies that specifically focus on non-communicable diseases within the Iranian population.

The association of body mass index variability with cardiovascular disease and mortality: a mediation analysis of pooled cohorts.

Aim: We aimed to investigate the effect of BMI variability on CVD and mortality and to explore the mediation effects of the main cardiovascular risk factors contributing to this association. Method: Participants aged 40-65 years were pooled from three cohort studies(ARIC [Atherosclerosis Risk in Communities], MESA [Multi-ethnic Study of Atherosclerosis], and TLGS [Tehran Lipid and Glucose Study]. We employed root mean squared error of the fractional mixed model to calculate BMI variability in the measurement period. In the event assessment period, the hazard ratios for CVD and mortality were estimated using Cox proportional hazard regression models. In the next step, the mediation and interaction effects of fasting plasma glucose, total cholesterol, and systolic blood pressure were determined. Results: A total of 19073 participants were included in this pooled analysis. During a median of 20.7 years of follow-up, 3900 (20.44%) CVD and 6480 (33.97%) all-cause mortality events were recorded. After adjusting for potential confounders, BMI variability was linked to the 1.3 (1.2-1.4) and 1.7 (1.6-1.8) increased risk of CVD and mortality, respectively. Fasting plasma glucose mediated approximately 24% and 8% of the effect of BMI variability on CVD and mortality, respectively. However, systolic blood pressure and total cholesterol did not have mediation effects in this association. Conclusion: High BMI variability is independently associated with the development of CVD and mortality. This association is partly mediated through fasting plasma glucose. Modern cardiometabolic therapies that lower fasting glucose may reduce the risk of future CVD and mortality in individuals with high BMI variability.

Impact of optimal cholesterol levels on subclinical atherosclerosis in the absence of risk factors in young adults.

BACKGROUND AND AIMS: We aimed to assess the association of blood lipids with the prevalence, incidence, and progression of subclinical atherosclerosis among young individuals without dyslipidemia and other traditional cardiovascular risk factors (CVRFs). METHODS: A total of 1270 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study aged 32-46 years free of cardiovascular disease, diabetes, hypertension, current smoking, and dyslipidemia (total cholesterol [TC] ≥ 240 mg/dL, triglycerides [TG] ≥ 150 mg/dL, low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL, high-density lipoprotein cholesterol [HDL-C] < 40 mg/dL, or taking lipid-lowering medications) were included. A subgroup with optimal lipids within the low-CVRF group was defined with TC < 200 mg/dL, LDL-C < 100 mg/dL, non-HDL-C < 130 mg/dL, and women with HDL-C ≥ 50 mg/dL. RESULTS: 1-SD higher TC (25.9 mg/dL), LDL-C (24.7 mg/dL), and non-HDL-C (26.6 mg/dL) were associated with a greater risk of presence (hazard ratios: 1.30-1.36), incidence (1.30-1.32), and progression (1.31-1.35) of coronary artery calcium (CAC) and a 42-44% greater odds of composite mean carotid intima-media thickness (CIMT) ≥ 75th percentile [780 µm] (p < 0.05). Repeating the analyses in a subset of participants with a CAC score of zero did not alter the association of TC, LDL-C, and non-HDL-C with CIMT. In the subgroup with optimal lipids, these lipid indices remained associated with an increased risk of presence and incidence of CAC and greater CIMT measures. CONCLUSIONS: Among adults aged 32-46 years, in the absence of traditional CVRFs, elevated cholesterol levels, even within what is considered optimal, are associated with atherosclerosis and arteriopathy.

The synergistic effect of obesity and dyslipidemia on hypertension: results from the STEPS survey.

BACKGROUND: Obesity and dyslipidemia are important risk factors for hypertension (HTN). When these two conditions coexist, they may interact in a synergistic manner and increase the risk of developing HTN and its associated complications. The aim of this study was to investigate the synergistic effect of general and central obesity with dyslipidemia on the risk of HTN. METHOD: Data from 40,387 individuals aged 25 to 64 years were obtained from a repeated cross-sectional study examining risk factors for non-communicable diseases (STEPS) in 2007, 2011 and 2016. Body mass index (BMI) was calculated as a measure of general obesity and waist circumference (WC) as a measure of central obesity. Dyslipidemia was defined as the presence of at least one of the lipid abnormalities. Hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or current use of antihypertensive medication. To analyze the synergistic effect between obesity and dyslipidemia and HTN, the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI) were calculated. A weighted logistic regression model was performed to estimate the odds ratios (ORs) for the risk of HTN. RESULTS: The results showed an association between obesity, dyslipidemia and hypertension. The interaction between obesity and dyslipidemia significantly influences the risk of hypertension. In hypertensive patients, the presence of general obesity increased from 14.55% without dyslipidemia to 64.36% with dyslipidemia, while central obesity increased from 13.27 to 58.88%. This interaction is quantified by RERI and AP values of 0.15 and 0.06 for general obesity and 0.24 and 0.09 for central obesity, respectively. The corresponding SI of 1.11 and 1.16 indicate a synergistic effect. The OR also show that the risk of hypertension is increased in the presence of obesity and dyslipidemia. CONCLUSION: Obesity and dyslipidemia are risk factors for HTN. In addition, dyslipidemia with central obesity increases the risk of HTN and has a synergistic interaction effect on HTN. Therefore, the coexistence of obesity and lipid abnormalities has many clinical implications and should be appropriately monitored and evaluated in the management of HTN.

Optimizing cardiovascular disease mortality prediction: a super learner approach in the tehran lipid and glucose study.

BACKGROUND & AIM: Cardiovascular disease (CVD) is the most important cause of death in the world and has a potential impact on health care costs, this study aimed to evaluate the performance of machine learning survival models and determine the optimum model for predicting CVD-related mortality. METHOD: In this study, the research population was all participants in Tehran Lipid and Glucose Study (TLGS) aged over 30 years. We used the Gradient Boosting model (GBM), Support Vector Machine (SVM), Super Learner (SL), and Cox proportional hazard (Cox-PH) models to predict the CVD-related mortality using 26 features. The dataset was randomly divided into training (80%) and testing (20%). To evaluate the performance of the methods, we used the Brier Score (BS), Prediction Error (PE), Concordance Index (C-index), and time-dependent Area Under the Curve (TD-AUC) criteria. Four different clinical models were also performed to improve the performance of the methods. RESULTS: Out of 9258 participants with a mean age of (SD; range) 43.74 (15.51; 20-91), 56.60% were female. The CVD death proportion was 2.5% (228 participants). The death proportion was significantly higher in men (67.98% M, 32.02% F). Based on predefined selection criteria, the SL method has the best performance in predicting CVD-related mortality (TD-AUC > 93.50%). Among the machine learning (ML) methods, The SVM has the worst performance (TD-AUC = 90.13%). According to the relative effect, age, fasting blood sugar, systolic blood pressure, smoking, taking aspirin, diastolic blood pressure, Type 2 diabetes mellitus, hip circumference, body mss index (BMI), and triglyceride were identified as the most influential variables in predicting CVD-related mortality. CONCLUSION: According to the results of our study, compared to the Cox-PH model, Machine Learning models showed promising and sometimes better performance in predicting CVD-related mortality. This finding is based on the analysis of a large and diverse urban population from Tehran, Iran.

Higher ultra-processed food intake is associated with an increased incidence risk of cardiovascular disease: the Tehran lipid and glucose study.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of death worldwide, although limited data are currently available regarding the impact of consuming ultra-processed food (UPF) on its incidence. Given the increased consumption of UPF in Iran, we aimed to investigate the association between UPF intake and CVD risk. METHODS: Individuals without CVD (n = 2050) aged ≥ 30 years old were recruited from the Tehran Lipid and Glucose Study (TLGS). Dietary data were collected using a validated food frequency questionnaire (FFQ) and UPF intakes were assessed based on the Nova food classification. Multivariable Cox proportional hazard models adjusted for potential confounders were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) for the risk of CVD across tertiles of UPF intake. RESULTS: A 10.1% incidence of CVD occurred over a median follow-up of 10.6 years, with a 22% increase in CVD risk per each 50 g/day UPF intake. Participants with the highest intake of UPF had a 68% greater incidence of CVD compared to those with the lowest intake (HR = 1.68, 95% CI=1.14-2.48) after controlling for potential confounders. Regarding sub-groups of UPF, participants in the 3rd tertile compared to the reference had a significantly increased risk of CVD (HR = 1.56, 95% CI=1.04-2.34). Nevertheless, intake of bread, fast food, sweetened beverages, sweets and desserts, high-fat dairy products, and other UPFs were not associated with greater CVD risk. CONCLUSION: Our findings support the hypothesis that the incidence of CVD is enhanced with the higher consumption of UPF in a representative sample of the Iranian population.

Establishing research impact assessment in Iran: The first report from a non-high-income country.

Background: This study presents the first report on research impact assessment (RIA) in non-high-income countries, undertaken as a pilot initiative in 2021. Within it, we aimed to explore the feasibility of employing the 'payback' model for evaluating the impact of health research and enhancing the accountability of universities. We focussed on three key impact domains: 'production of decision support documents and knowledge-based products,' 'implementation of research results,' and 'health and economic impact.' Methods: We adopted a case study approach to assess the impact of 5334 health research projects conducted by researchers from 18 universities from 2018 to 2020. Researchers were required to submit evidence related to at least one of the specified impact domains; six scientific committees verified and scored claimed impacts at the national level. Results: Only 25% of the assessed projects achieved impact in at least one domain, with the production of decision support documents and knowledge products being the most reported impact. Notably, economic impact was verified in only three projects, indicating room for improvement in this area. Technology research exhibited the highest acceptance rate of claimed impact, suggesting a positive correlation between technology-focused projects and impactful outcomes. Conclusions: This study demonstrates the feasibility of employing a case study approach and the 'payback' model to evaluate the impact of health research, even within the constraints of a moderately equipped research infrastructure. These findings underscore the potential of integrating RIA into the governance of health research in Iran and other non-high-income countries, as well as the importance of using RIA to assess the accountability of health research systems, guide the allocation of research funding, and advocate for the advancement of health research. The study sets a precedent for future assessments in similar contexts and contributes to the ongoing global dialogue on the societal impact of health research.

The Tehran longitudinal family-based cardiometabolic cohort study sheds new light on dyslipidemia transmission patterns.

Dyslipidemia, as a metabolic risk factor, with the strongest and most heritable independent cause of cardiovascular diseases worldwide. We investigated the familial transmission patterns of dyslipidemia through a longitudinal family-based cohort, the Tehran Cardiometabolic Genetic Study (TCGS) in Iran. We enrolled 18,729 individuals (45% were males) aged > 18 years (mean: 38.15 (15.82)) and observed them over five 3-year follow-up periods. We evaluated the serum concentrations of total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol with the first measurement among longitudinal measures and the average measurements (AM) of the five periods. Heritability analysis was conducted using a mixed-effect framework with likelihood-based and Bayesian approaches. The periodic prevalence and heritability of dyslipidemia were estimated to be 65.7 and 42%, respectively. The likelihood of an individual having at least one dyslipidemic parent reveals an OR = 6.94 (CI 5.28-9.30) compared to those who do not have dyslipidemic parents. The most considerable intraclass correlation of family members was for the same-sex siblings, with ICC ~ 25.5%. For serum concentrations, heritability ranged from 33.64 to 60.95%. Taken together, these findings demonstrate that familial transmission of dyslipidemia in the Tehran population is strong, especially within the same-gender siblings. According to previous reports, the heritability of dyslipidemia in this population is considerably higher than the global average.

The difference between 2-hour post-challenge and fasting plasma glucose associates with the risk of cardiovascular disease in a normoglycemic population: the Tehran lipid and glucose study.

BACKGROUND: Elevated fasting plasma glucose (FPG) and 2-hour post-challenge glucose (2hPG) levels are known to be independent risk factors for cardiovascular disease (CVD). However, there is limited data on the association of the difference between these measures and the risk of CVD. This study aims to investigate this association in normoglycemic Iranian adults, particularly in those with low-normal FPG levels. METHODS: This prospective cohort study included 4,594 30-65-year-old participants from the Tehran Lipid and Glucose Study. Using multivariable Cox proportional hazards regression models adjusting for age, sex, body mass index, hypertension, hypercholesterolemia, smoking, education level and FPG, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the association between 2hPG-FPG, both as continuous and categorical variables, and the CVD risk. Analyses of receiver operating characteristic curves were undertaken to determine the optimal 2hPG-FPG cut-off value. RESULTS: During a median of 17.9 years of follow-up, 459 CVD events occurred. A one-unit increase in 2hPG-FPG was significantly associated with an elevated risk of cardiovascular disease in both normoglycemic (HR 1.10, 95% CI (1.01-1.19)) and low-normal FPG individuals (HR 1.16, 95% CI (1.04-1.30)); this association resisted adjustment for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) among normoglycemic individuals. However, those with 2hPG levels greater than FPG levels had a non-significant increased risk of incident CVD compared to those with 2hPG levels of less than or equal to FPG, with corresponding HR values of 1.18 (95% CI: 0.95-1.46) in normoglycemic and 1.32 (95% CI: 0.98-1.79) in low-normal FPG, respectively. For incident CVD, the optimal cut-off value for the 2hPG-FPG was found to be 1.06 mmol/L, which was applicable for both normoglycemic and low FPG populations; using this criterion, the corresponding risks for incident CVD were 1.36 (95% CI: 1.12-1.64) and 1.57 (95% CI: 1.22-2.03), respectively. CONCLUSIONS: The difference between 2hPG and FPG levels within the normoglycemic range is related to an increased risk of CVD, an issue that was independent of HOMA-IR. A cut-off point for 2hPG-FPG > 1.06 mmol/L may stratify persons at higher risk. These findings were particularly notable in those with low-normal FPG.

Impact of coronary artery calcium on mortality and cardiovascular events in metabolic syndrome and diabetes among younger adults.

AIMS: Whether coronary artery calcium (CAC) testing in younger individuals with metabolic syndrome (MetS) and diabetes mellitus (DM) helps predict cardiovascular disease (CVD) and death independent of traditional risk factors (RFs) remains less clear. METHODS AND RESULTS: We pooled data obtained from 5174 individuals aged 38-55 years from the CARDIA (Coronary Artery Risk Development in Young Adults; n = 3047, year 20) and MESA (Multi-Ethnic Study of Atherosclerosis; n = 2127, Visit 1) studies who completed computed tomography of CAC. The mean age (SD) of participants (44.7% men) was 47.3 (4.2) years. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of CVD, coronary heart disease (CHD), and all-cause death. There were 1085 participants (21.0%) with prevalent CAC at baseline. A total of 461 (8.9%) had DM, 1025 (19.8%) had MetS without DM, and 3688 (71.3%) had neither condition. Over a median follow-up of 14.2 years, 256 (5.0%) participants died, and 304 (5.9%) CVD and 188 (3.6%) CHD events occurred. The CAC score was independently associated with incident CVD in those with DM (HR: 95% CI; 1.22: 1.08-1.38), MetS (1.18: 1.08-1.31), and neither condition (1.36: 1.26-1.46). The corresponding HRs for CAC ≥ 100 were 2.70 (1.25-5.83), 3.29 (1.87-5.79), and 6.30 (4.02-9.86), respectively. Similar associations for CHD and death were found. The impact of CAC ≥ 100 on CVD and CHD was lower in the presence of DM (P interaction < 0.05). The association of CAC with all outcomes in individuals with DM remained significant after adjusting with haemoglobin A1c levels. CONCLUSION: Coronary artery calcium score is independently associated with cardiovascular events and death over nearly 15 years after screening at ages 38-55 years, with a less pronounced impact on CVD and CHD events in the presence of DM.

In this pooled cohort, we aimed to analyse the relationship between coronary artery calcium (CAC) and incidence of cardiovascular disease (CVD), coronary heart disease (CHD), and all-cause mortality among younger individuals with diabetes mellitus (DM), metabolic syndrome (MetS), and neither condition. The CAC score was independently associated with incident CVD, CHD, and all-cause mortality in those with DM, MetS, and neither condition. The impact of CAC ≥ 100 on CVD and CHD events was lower in the presence of DM. The association of CAC with all outcomes in individuals with DM remained significant after adjusting with haemoglobin A1c levels.

The impact of obesity on different glucose tolerance status with incident cardiovascular disease and mortality events over 15 years of follow-up: a pooled cohort analysis.

BACKGROUND: The effect of obesity in different glucose tolerance statuses i.e. normoglycemia (NGT), pre-diabetes, and type 2 diabetes (T2DM) on cardiovascular disease (CVD) and mortality has been an area of ongoing debate and uncertainty. In the present study, we aimed to examine the impact of being obese, whether general or central separately, in comparison with non-obese in different glucose tolerance statuses on the above outcomes. METHODS: The study population included 18,184 participants aged 30-60 years (9927 women) from three longitudinal studies, including Atherosclerosis Risk in Communities, Multi-Ethnic Study of Atherosclerosis, and Tehran Lipid and Glucose Study. Glucose tolerance status was defined as NGT (fasting plasma glucose < 5.55 mmol/L), pre-diabetes (5.55-7.00 mmol/L), and T2DM (≥ 7 mmol/L or taking any medication for diabetes). Moreover, general and central obesity were defined based on body mass index and waist circumference (WC), respectively. Multivariable stratified Cox regression analysis was used to estimate hazard ratios (HRs (95% CI)) for CVD and mortality events. RESULTS: During a 16-year follow-up, 2733 CVD events, 1101 CV mortality, and 3678 all-cause mortality events were recorded. We observed that being generally obese in comparison with non-obese increased the risk of CV and all-cause mortality in all glucose tolerance statuses; while considering CVD events, only among individuals with T2DM, the presence of general obesity was associated with marginally significant higher risk [1.19 (0.98-1.43); p-value = 0.07]. Regarding central adiposity, multivariate analysis revealed that elevated WC in NGT participants is associated with incident CVD [1.27(1.12-1.46)] and all-cause mortality [1.13(1.00-1.28)]. Moreover, central adiposity increased the risk of CV mortality in pre-diabetes individuals [1.47 (1.11-1.95)]. CONCLUSION: Findings from this pooled prospective cohort studies provide evidence that general obesity shows an unfavorable association with CV and all-cause mortality among the general population irrespective of their glucose tolerance statusThe findings imply that it's important to take into account the requirement and magnitude of weight reduction in people who are obese when offering guidance.

Alterations in CD4+ T Cell Cytokines Profile in Female Patients with Hashimoto's Thyroiditis Following Vitamin D Supplementation: A Double-blind, Randomized Clinical Trial.

BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune disease characterized by the destruction of thyroid cells through immune processes involving T helper (Th)1 cytokines. This clinical trial investigates the impact of vitamin D supplementation on serum cytokine levels and gene expression in CD4+ T cells from HT patients, aiming to understand its effects on Th-1, Th-2, Th-17, and regulatory T (Treg) cell-associated factors. METHODS: Female patients were randomly assigned in a double-blind design to either a vitamin D-supplemented group, which received cholecalciferol [1, 25(OH)2D3] at a dose of 50,000 IU, or the placebo group, which received a weekly placebo for a duration of three months. Serum cytokine levels were assessed using enzyme-linked immunosorbent assay (ELISA), while genes' expression levels were measured using real-time PCR. RESULTS: Serum 25-hydroxyvitamin D and levels exhibited a significant increase following vitamin D supplementation, in comparison to the placebo group. Additionally, the vitamin D supplementation resulted in a significant elevation of serum calcium (Ca) levels compared to baseline. In the vitamin D group, there was a significant decrease in both serum levels and expression of the interleukin (IL)-17 gene when compared to baseline, although no statistical difference was observed between the placebo and vitamin D groups. The gene expression of transforming growth factor-beta (TGFß) was significantly increased in the vitamin D group compared to baseline, with no significant difference between the two study groups. Vitamin D treatment had no effect on serum levels of interferon-gamma (IFNϒ) and IL-4. While the gene expression of IL-4 in the vitamin D group did not exhibit a statistically significant increase, the level of GATA3 transcription factor increased significantly when compared to the placebo group. The expression of IFNϒ and transcription factors, T-bet, RORc, and forkhead box protein 3 (FOXP3) in genes did not show significant changes following vitamin D supplementation. CONCLUSION: The findings suggest that vitamin D supplementation may hold potential benefits for autoimmune diseases, such as HT. However, further longitudinal clinical trials are necessary to gain a more comprehensive understanding of the specific effects of vitamin D on HT. CLINICAL TRIAL REGISTRATION NUMBER: IRCT2016110130644N1.

Risk of recurrence at the time of withdrawal of short- or long-term methimazole therapy in patients with Graves' hyperthyroidism: a randomized trial and a risk-scoring model.

PURPOSE: In Graves' disease, administration of low-dose methimazole for more than 60 months induces higher remission rates compared with the conventional duration of 12-18 months. However, the risk of recurrence and its predictors beyond 48 months of drug withdrawal are not known. The aims of this study were to determine the risk of recurrence during 84 months after withdrawal of short- or long-term methimazole therapy and a risk stratification for recurrence of hyperthyroidism. METHODS: A total of 258 patients were treated with methimazole for a median of 18 months and randomized to discontinuation of the drug(conventional short-term group; n = 128) or continuation of the treatment up to 60-120 months(long-term group; n = 130). Patients were followed for 84 months after methimazole withdrawal. Cox proportional hazards modeling was performed to identify factors associated with relapse and develop a risk-scoring model at the time of discontinuing the treatment. RESULTS: Hyperthyroidism recurred in 67 of 120(56%) of conventionally-treated patients versus 20 of 118(17%) of those who received long-term methimazole treatment, p < 0.001. Age, sex, goiter grade, triiodothyronine, thyrotropin, and thyrotropin receptor antibodies were significant predictors of recurrence in both "conventional" and "long-term" groups but free thyroxine just in the "long-term" group. The risk-scoring model had a good discrimination power (optimism corrected c-index = 0.78,95%CI = 0.73-0.82) with a range of 0-14 and sensitivity of 86% and specificity of 62% at the risk-score of eight. CONCLUSION: A relapse-free state was achieved in 83% of patients with Graves' hyperthyroidism 84 months after cessation of long-term methimazole treatment which could be predicted by some significant predictors in a simple risk-scoring system.

Gender differences in midlife to later-life cumulative burden and variability of obesity measures and risk of all-cause and cause-specific mortality.

BACKGROUND/OBJECTIVES: Previous studies have reported the gender-specific association between general and central obesity measures, using snapshot assessments, and mortality events. This study seeks to further explore this link by examining how the longitudinal cumulative burden and variability of obesity measures from midlife to later-life impact mortality events in the Atherosclerosis Risk in Communities (ARIC) study population, specifically in relation to gender differences. SUBJECTS/METHODS: Using data from the ARIC study, a total of 7615 (4360 women) participants free of cardiovascular disease, cancer, and early mortality events were included in the data analysis. Longitudinal cumulative burden (estimated by the area under the curve (AUC) using a quadratic mixed-effects method) and variability (calculated according to average successive variability (ASV)) were considered as exposures, separately and all together. Cox proportional hazard regression models were used to estimate multivariable-adjusted standardized hazard ratios. RESULTS: The mean age was 62.4 and the median follow-up was 16.9 years. In men, AUCs of waist-related obesity measures, and also ASVs of all obesity measures were associated with increased all-cause mortality risk. In women, waist circumference and waist-to-height ratio AUCs were associated with increased all-cause mortality risk. Regarding cardiovascular mortality, all adiposity measures ASVs in both genders and waist-related obesity measures AUCs in men were associated with increased risk. Significant gender differences were found for the associations between cumulative and variability of waist-to-hip ratio for all-cause mortality and all adiposity measures ASVs for cardiovascular mortality risk with higher impact among men. CONCLUSIONS: Cumulative burden and variability in general and central obesity measures were associated with higher all-cause and cardiovascular mortalities among men. In women, general obesity measures variability, as well as cumulative and variability of central adiposity measure, increased all-cause mortality risk.

Cumulative Blood Pressure in Early Adulthood and Coronary Artery Calcium and Carotid Intima-Media Thickness in Middle Age Among Adults With Maintained Blood Pressure of <130/80 mm Hg: A Post Hoc Analysis.

BACKGROUND: To examine the association of blood pressure (BP) levels with coronary artery calcium and carotid intima-media thickness (CIMT) in people with maintained BP below the hypertension range based on current definitions. METHODS AND RESULTS: In this post hoc analysis of the CARDIA (Coronary Artery Risk Development in Young Adults) prospective observational cohort study conducted in 4 US cities, we examined 1233 study participants (mean [SD] age at year 20 examination was 45.3 [3.5] years; 65.4% women). Participants with BP assessments across 20 years and untreated BP of <130/80 mm Hg were included. Multivariable logistic or linear regression models, adjusted for age, sex, race, education, diabetes, body mass index, serum creatinine, smoking, alcohol intake, physical activity, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides, were used to examine the associations between cumulative BP measures with coronary artery calcium and CIMT. Higher long-term cumulative systolic BP and pulse pressure across early adulthood were associated with higher CIMT (both P<0.001) but not coronary artery calcium in the multivariable-adjusted model. The associations remained significant even after adjustment for a single BP measurement at year 0 or year 20. The odds ratio (OR) of a maximal CIMT >1.01 mm was ≈50% higher per 1-SD increase in systolic BP (OR, 1.50 [95% CI, 1.19-1.88]) and pulse pressure (OR, 1.46 [95% CI, 1.19-1.79]). Similar findings for CIMT were observed among individuals with a coronary artery calcium score of 0 as well as those with maintained BP of <120/80 mm Hg throughout young adulthood. CONCLUSIONS: Long-term cumulative systolic BP and pulse pressure across early adulthood within the nonhypertensive range were associated with adverse midlife alterations in CIMT.

Factors associated with smoking intensity among adult smokers: findings from the longitudinal cohort of the Tehran lipid and glucose study.

BACKGROUND: Smoking is a significant public health problem, and there is a scarcity of documents regarding its severity, particularly in developing countries. This study aimed to determine factors related to the number of cigarettes consumed daily by adult smokers in Tehran. METHODS: This study was conducted within the framework of the longitudinal study of Tehran Lipid and Glucose Study (TLGS). The study included 786 adult smokers living during four consecutive follow-ups from 2005 to 2016. The intensity of smoking was measured by the number of cigarettes consumed daily by adult smokers. Data analysis was done longitudinally and based on the mixed effects zero-inflated discrete Weibull (ZIDW) regression model. RESULTS: The mean age of the individuals was 40.35 ± 12.68 years, and 643 (81.8%) of them were men. Also, 52.7% of individuals were daily smokers, 15.6% were occasional smokers, and 31.7% were non-smokers who became smokers during the study. Variables of age 1.005 (95%CI: 1.001-1.008), gender of male 1.196 (95%CI: 1.051-1.39), and marital status (divorced/widowed vs. single) 1.168 (95%CI: 1.015-1.39) were positively associated with smoking intensity. Education level (master and higher vs. illiterate) 0.675 (95%CI: 0.492-0.926)), employment status (student vs. unemployed) 0.683 (95%CI: 0.522-0.917), (housewife vs. unemployed) 0.742 (95%CI: 0.606-0.895), (Unemployed with income vs. unemployed) 0.804 (95%CI: 0.697, 0.923), implementation of smoking prohibition regulations (yes vs. no) 0.88 (95%CI: 0.843-0.932), and history of cardiovascular disease in male relatives (yes vs. no) 0.85 (95%CI: 0.771-0.951) were associated with lower smoking intensity. CONCLUSION: We showed that demographic factors are associated with the intensity of smoking among adults and should be considered in policymakers' intervention programs to reduce smoking and quit smoking.