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.

Usual intake of dairy products and the chance of pre-diabetes regression to normal glycemia or progression to type 2 diabetes: a 9-year follow-up.

BACKGROUND: We assessed the possible effect of usual dairy consumption on pre-diabetes (Pre-DM) remission or progression to type 2 diabetes (T2D). METHODS: Pre-DM adults (n = 334, mean age of 49.4 years, and 51.5% men) were assessed for dairy intakes (2006-2008) and followed up to 9 years for incidence of T2D or normal glycemia (NG). All biochemical measurements were done at baseline and all subsequent examinations with 3-y follow-up intervals. Multinomial regression models with adjustment of confounding variables were used to estimate odds ratios (OR) and 95% confidence intervals (CIs) of incident T2D and NG for each serving/d dairy consumption. RESULTS: The odds of NG was significantly elevated by 69% (OR = 1.69, 95% CI = 1.00-2.86, P = 0.05) per 200 g/d increased high-fat dairy intake, while the amount of total dairy or low-fat dairy was not related to the outcomes. Higher intakes of yogurt were more likely to be associated with an increased odds of NG (OR = 1.82, 95% CI = 1.20-2.74, P = 0.01). Usual intakes of milk, cheese, or cream-butter were not associated to Pre-DM remission or progression to T2D. CONCLUSION: Regular dairy consumption may increase the chance of Pre-DM regression to NG.

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.

Metabolic health's central role in chronic kidney disease progression: a 20-year study of obesity-metabolic phenotype transitions.

This study investigates the risk of chronic kidney disease (CKD) across four metabolic phenotypes: Metabolically Healthy-No Obesity (MH-NO), Metabolically Unhealthy-No obesity (MU-NO), Metabolically Healthy-Obesity (MH-O), and Metabolically Unhealthy-Obesity (MU-O). Data from the Tehran Lipid and Glucose Study, collected from 1999 to 2020, were used to categorize participants based on a BMI ≥ 30 kg/m2 and metabolic health status, defined by the presence of three or four of the following components: high blood pressure, elevated triglycerides, low high-density lipoprotein, and high fasting blood sugar. CKD, characterized by a glomerular filtration rate < 60 ml/min/1.72 m2. The hazard ratio (HR) of CKD risk was evaluated using Cox proportional hazard models. The study included 8731 participants, with an average age of 39.93 years, and identified 734 incidents of CKD. After adjusting for covariates, the MU-O group demonstrated the highest risk of CKD progression (HR 1.42-1.87), followed by the MU-NO group (HR 1.33-1.67), and the MH-O group (HR 1.18-1.54). Persistent MU-NO and MU-O posed the highest CKD risk compared to transitional states, highlighting the significance of exposure during early adulthood. These findings emphasize the independent contributions of excess weight and metabolic health, along with its components, to CKD risk. Therefore, preventive strategies should prioritize interventions during early-adulthood.

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.

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.

Association of ideal cardiovascular health metrics with incident low estimated glomerular filtration rate: More than a decade follow-up in the Tehran Lipid and Glucose Study (TLGS).

AIMS: To evaluate the association between ideal cardiovascular health metrics (ICVHM) and incident low estimated glomerular filtration rate (eGFR) among the Iranian population. METHODS: The study population included 6927 Iranian adults aged 20-65 years (2942 male) without prevalent low eGFR [i.e., eGFR < 60 ml/min/1.73 m2] and free of cardiovascular disease. The ICVHM was defined according to the 2010 American Heart Association. The multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratios (HRs) of ICVHM both as continuous and categorical variables. RESULTS: Over the median of 12.1 years of follow-up, we found 1259 incident cases of low eGFR among the study population. In this population, ideal and intermediate categories of body mass index (BMI) and blood pressure (BP) and only the ideal category of fasting plasma glucose (FPG) significantly decreased the risk of developing low eGFR; the corresponding HRs and (95% confidence intervals) were (0.87, 0.77-0.99), (0.84, 0.76-0.99), (0.79, 0.68-0.93), (0.70, 0.60-0.83) and (0.76, 0.64-0.91). Also, one additional ICVHM was associated with a reduced risk of low eGFR for the global (0.92, 0.88-0.97) and biological cardiovascular health (0.88, 0.82-0.93) in these participants. A sensitivity analysis using the interval-censoring approach demonstrated that our method is robust, and results remained essentially unchanged. In a subgroup population with dietary data (n = 2285), we did not find the beneficial impact of having intermediate/ideal categories of nutrition status compared to its poor one on incident low eGFR. CONCLUSION: We found a strong inverse association between having higher global ICVHM with incident low eGFR among the non-elderly Iranian population; the issue is mainly attributable to normal BP, BMI, and FPG levels.

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.

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.

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.

A prospective study on the relationship between polycystic ovary syndrome and age at natural menopause.

OBJECTIVE: This study aimed to determine whether polycystic ovary syndrome (PCOS) was associated with age at menopause, compared with women without PCOS, after adjusting for potential confounders. METHODS: A total of 1,696 reproductive-aged participants from the Tehran Lipid and Glucose Study were included in this population-based prospective study with a follow-up of approximately 20 years. Of these, 348 women with PCOS based on the Rotterdam criteria and 1,348 non-PCOS controls were followed to assess the age at which they reached menopause. An accelerated failure time survival regression model was used to identify the association between PCOS and the age at natural menopause (ANM), with and without adjustment for potential confounders. RESULTS: The unadjusted accelerated failure time survival model revealed a significant positive association between PCOS and ANM; PCOS women experienced time to menopause by a factor of 1.05 than non-PCOS controls (95% confidence interval, 1.02-1.06; P < 0.001). After adjusting for age at baseline, menarche age, history of hypertension, history of type 2 diabetes mellitus, parity, oral contraceptive use, body mass index, education level, physical activity, and smoking, the results remained significant (time ratio: 1.03; 95% confidence interval, 1.01-1.06; P = 0.002). CONCLUSIONS: This study indicates that ANM is significantly associated with PCOS in women. Our study findings may have implications for the fertility and reproductive health of women with PCOS. However, further large longitudinal studies on diverse populations accounting for other relevant confounders are still needed to provide data on the actual difference in age at menopause and to elucidate the underlying mechanisms of this association.

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.

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.

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.

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.

Statins and thyroid eye disease (TED): a systematic review.

PURPOSE: Thyroid eye disease (TED) is the foremost extrathyroidal manifestation of Graves' disease (GD). Currently, available treatments do not entirely prevent the long-term consequences of TED and have distinct disadvantages. Therefore, this systematic review explored available evidence regarding the efficacy of statins in preventing and treating TED. METHODS: Relevant studies investigating statin usage in patients with GD or TED were identified by searching Medline (Pubmed and Ovid), Scopus, Web of Science, ProQuest, and Cochrane Library databases (from the database inception to September 2023). The review was done according to the PRISMA statement. Web searching was done independently by two investigators. Two researchers independently extracted the data, and any disagreement was adjudicated by consensus. Based on the study design, the studies' quality appraisal was done using the Newcastle-Ottawa Scale (NOS) and Version 2 of the Cochrane risk-of-bias tool (RoB2). RESULTS: The literature search identified 145 publications, of which four met the inclusion criteria (Three retrospective cohort studies and one randomized clinical trial) and were reviewed in full text. The two retrospective cohort studies demonstrated the beneficial effects of statins on TED in newly diagnosed GD Stein et al. showed that statins, regardless of the type, prevent or delay TED (HR: 0.74 (0.65-0.84)), especially in men or treatment duration of more than one year. Nilsson et al. fascinatingly revealed that at least 60 days of statin usage in the preceding year could decrease the risk of TED development by around 40%. One RCT showed a higher treatment response for active moderate-to-severe TED in patients with hypercholesterolemia who took atorvastatin 20 mg in addition to ivGC for 24 weeks without any increase in serious side effects. The retrospective study revealed that the need for reconstructive surgery was reduced in patients with severe TED who received statin therapy. CONCLUSION: Statin therapy could be a potential adjunctive modality for preventing and treating TED. TRIAL REGISTRATION: PROSPERO registration number: CRD42022315522.

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.

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.

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.

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.