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

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

Comparative analysis of adolescent hypertension definitions for predicting early-adulthood carotid artery intima-media thickness: Tehran lipid and glucose study.

Background: Definitions of childhood and adolescent hypertension (HTN) do not precisely elucidate the relationship between HTN and cardiovascular outcomes. Carotid intima-media thickness (CIMT), as a substitute for cardiovascular outcomes, enables the early identification of cardiovascular events throughout early adulthood. Purpose: This study aimed to compare the ability of childhood HTN definitions to predict a high CIMT in early adulthood. Methods: This prospective cohort study included 921 individuals aged 10-17 years from the Tehran Lipid and Glucose Study (TLGS). The CIMT was measured after 18 years of follow-up. Participants were categorized into normal blood pressure (BP), high-normal BP, HTN stage 1, and HTN stage 2 groups based on the childhood HTN definitions of the 4th report, European Society of Hypertension (ESH), and American Academy of Pediatrics Clinical Practice Guidelines (AAP-CPG). Akaike's information criterion (AIC) and relative efficiencies (RE) were calculated to compare the ability of each to predict a high CIMT (≥95th percentile) during early adulthood. Results: The highest and lowest prevalence of stage 1 HTN was observed with the AAP-CPG (17.7%) and ESH (8.8%), respectively. Similarly, the highest and lowest prevalence of stage 2 HTN was noted with the AAP-CPG (1.5%) and ESH (0.8%), respectively. According to the RE values, the highest to lowest predictive abilities belonged to the 4th report, ESH, and AAP-CPG, respectively. In all models, the 4th report's pediatric HTN definition had the lowest AIC value and offered the best predictive ability. Conclusion: Among the various definitions of pediatric HTN, the 4th report offered the best ability to predict a high CIMT during early adulthood, followed by the ESH and AAP-CPG. Because the reference population of the 4th report includes overweight, obese, and normal-weight individuals, our findings suggest that excessive adiposity is among the main predictors of early adulthood atherosclerosis risk.

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

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

Association of obesity severity and duration with incidence of chronic kidney disease.

INTRODUCTION: Obesity is a known risk factor for chronic kidney disease (CKD), but the impact of obesity severity and duration on CKD incidence is unclear. METHODS: Cumulative Excess Weight (CEW) and Cumulative Excess Waist Circumference (CEWC) scores were calculated, which represent the accumulation of deviations from expected body mass index and waist circumference values over time until the development of CKD or the end of the follow-up period. Time-dependent Cox models were used to investigate the sex-stratified association of CEW and CEWC with CKD incidence while controlling for confounding variables. RESULTS: Out of the 8697 participants who were evaluated in this study, 56% (4865) were women and the mean age was 40 ± 14. During the 15-year follow-up period, 41.7% (3629) of the participants developed CKD. Among the CKD patients, 65.4% (829) of men and 77.9% (1839) of women had a BMI higher than 25, and high WC was found to be 73.7% (934) and 55.3% (1306) for men and women, respectively. We found a significant association between one standard deviation change of CEW and the development of CKD in both sexes (fully adjusted hazard ratios and 95% CI of CEW in men and women were 1.155 [1.081-1.232) and 1.105 (1.047-1.167)]. However, the association between CEWC and CKD development was only significant among men participants [HR = 1.074 (1.006-1.147)]. CONCLUSION: Over a 15-year follow-up, the accumulation of general and central obesity was associated with an increased incidence of CKD development.

Linking extent of return to fasting state after oral glucose tolerance test to future risk of prediabetes and type 2 diabetes: Insights from the TLGS.

AIMS: To assess the risk of difference between 2 h post-load plasma glucose (2 h-PG) and fasting plasma glucose (FPG) on incident prediabetes/type 2 diabetes (T2DM) among normoglycemic individuals. METHODS: Among 4,971 individuals aged ≥20 years, the associations of the difference between 2 h-PG and FPG with outcomes were examined using multivariable-adjusted Cox regression analysis. Participants were categorized into three groups: a low post-load group (2 h-PG ≤ FPG, as the reference group); a high post-load group (2 h-PG > FPG and ≥75th percentile of the difference); and a medium post-load group (2 h-PG > FPG and <75th percentile of the difference), which was further categorized into three groups by equal ranges. RESULTS: Over a median of 11.5 years of follow-up, 2,331 new cases of prediabetes/type 2 diabetes and 360 cases of type 2 diabetes occurred. Greater risks of incident prediabetes/type 2 diabetes in second (9-16 mg/dL) and third (17-24 mg/dL) medium post-load, as well as high post-load (≥25 mg/dL) categories, were found, with hazard ratios (95% confidence intervals) of 1.26 (1.11-1.44), 1.32 (1.15-1.51), and 1.69 (1.51-1.90), respectively; the issue was more prominent among women (P for interaction = 0.005). The risk of incident type 2 diabetes was also higher for these categories. After further adjustment for the homeostasis model assessment of insulin resistance, result remained essentially unchanged. Even among individuals with low normal FPG (i.e., <90 mg/dL), ≥9 mg/dL difference between 2 h-PG and FPG increased the risk of composite prediabetes/ type 2 diabetes. CONCLUSIONS: Greater levels of 2 h-PG as low as 9 mg/dL than FPG among normoglycemic individuals is a harbinger of prediabetes/type 2 diabetes development.

Systemic nitric oxide metabolites and the chance of pre-diabetes regression to normoglycemia: A 9-year cohort study.

Introduction: We aimed to track longitudinal changes of glycemic status in subjects with pre-diabetes (Pre-DM) in relation to their baseline levels of systemic nitric oxide (NO) production [i.e., measured as serum NO metabolites (NOx), crude and body weight (BW)-adjusted NOx to creatinine ratio (NOx-to-Cr)] over 9 years. Methods: This cohort study included 541 middle-aged Iranian men and women with Pre-DM, recruited in 2006-2008 and followed up to 2015-2017. The colorimetric Griess method was used to measure serum NOx concentration. Multinomial logistic regression analyses estimated the odds ratios (OR) of Pre-DM regression and progression across tertiles (tertile 3 vs. tertile 1 and tertile 2) of serum NOx, crude, and BW-adjusted NOx-to-Cr ratio. Results: Participants who regressed to normoglycemia (NG) had a higher BW-adjusted NOx-to-Cr ratio than those who developed type 2 diabetes (T2D) or those who remained Pre-DM (0.52±0.34 vs. 0.43±0.25 and 0.48±0.29, P=0.023). Higher BW-adjusted NOx-to-Cr increased chance of returning to NG (OR=2.05, 95% CI= 0.98-4.32, P=0.058) and decreased levels of 2h-serum glucose over time (P time×group=0.025), as well as the decreased overall mean of fasting (106, 95% CI=103-109 vs. 110, 95% CI=108-112 mg/dL, P=0.008) and 2h-serum glucose (153, 95% CI=146-159 vs. 163, 95% CI=158-168 mg/dL, P=0.018). Conclusion: A higher endogenous NO production (i.e., indirectly measured by BW- and Cr-adjusted serum NOx concentration) in Pre-DM subjects is associated with the chance of returning to NG.

Independent association of metabolic syndrome severity score and risk of diabetes: findings from 18 years of follow-up in the Tehran Lipid and Glucose Study.

OBJECTIVES: This study aimed to investigate the association between age-specific and sex-specific continuous metabolic syndrome severity score (cMetS-S) and the risk of developing type 2 diabetes mellitus (T2DM). Additionally, the study aimed to assess the added value of cMetS-S in predicting T2DM compared with traditional MetS criteria. DESIGN: The study used a longitudinal cohort design, following participants for 18 years. SETTING: The research was conducted within the Tehran Lipid and Glucose Study, a community-based study in Tehran, Iran. PARTICIPANTS: A total of 6957 participants aged 20-60 years were included in the study. INTERVENTIONS/EXPOSURES: The cMetS-S of each participant was determined using age-specific and sex-specific equations and Cox proportional hazard regression models were used to analyse the association between cMetS-S and T2DM using continuous and quantile approaches. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measure was the association between cMetS-S and the development of T2DM during the 18-year follow-up. RESULTS: A total of 1124 T2DM cases were recorded over 18 years of follow-up. In the fully adjusted model, a 1-SD increase in the cMetS-S was associated with future T2DM (HR 1.72; 95% CI 1.54 to 1.91). Men and women had HRs of 1.65 (95% CI 1.40 to 1.95) and 1.83 (95% CI 1.59 to 2.10) for T2DM per 1-SD increase in cMetS-S, respectively. Higher cMetS-S was associated with increased risk of diabetes in both prediabetic (HR 1.42;95% CI 1.23 to 1.64) and normoglycaemic individuals (HR 2.11;95% CI 1.76 to 2.54); this association was more significant in normoglycaemic individuals. Unlike the traditional-based MetS definitions, the cMetS-S improved diabetes prediction (p<0.001). CONCLUSIONS: The cMetS-S is strongly associated with future diabetes in prediabetic and normoglycaemic individuals independent of MetS components during a long term. As the relationship between cMetS-S and T2DM is more pronounced in normoglycaemic individuals than in those with pre-diabetes, implementing the evaluation of cMetS-S can serve as an early identification tool for individuals at risk of T2DM prior to the onset of pre-diabetes.

The association of body weight change and regression to normoglycemia in different phenotypes of pre-diabetes: Findings of a longitudinal cohort study.

AIM: We investigated the association of a 3-year change in body weight (BW) and regression to normal glucose regulation (NGR) among different phenotypes of pre-diabetes (Pre-DM), i.e., isolated impaired glucose tolerance (iIGT), isolated impaired fasting glucose (iIFG) and combined IFG-IGT. RESEARCH DESIGN AND METHODS: 1458 Pre-DM subjects (iIFG = 618, iIGT = 462, and IFG-IGT = 378) were assessed for 3-year change-percent in BW (2006-2008 to 2009-2011) and then followed up to 2015-2017, within the national cohort of Tehran Lipid and Glucose Study (TLGS). Binary logistic regression models were used to estimate the probability (odds ratio, ORs) of regression to NGR across categories of 3-year BW change (i.e., ≥5% BW loss, <5% BW loss, BW gain) in different phenotypes of Pre-DM. RESULTS: The mean age of the participants was 53.0 ± 13.7, and 46.8% were men. Over a median of 6 years of follow-up, the rate of regression to normoglycemia was 50.6, 43.2, and 12.7% in iIGT, iIFG, and combined IFG-IGT, respectively. The baseline-adjusted mean of 3-year BW change was not significantly different across Pre-DM phenotypes (0.68 ± 0.19, 0.32 ± 0.22, and 0.23 ± 0.24 kg, in iIFG, iIGT, and IFG-IGT). Three-year BW loss ≥5% was associated with a greater NGR probability in iIGT than other phenotypes (OR = 4.29 vs. 3.90 and 2.84 in IFG-IGT and iIFG, respectively). A modest reduction (<5% of initial BW) resulted in an increased chance of Pre-DM regression among subjects with iIGT (OR = 1.61, 95% CI = 1.03-2.52) but not iIFG or IFG-IGT phenotypes. CONCLUSION: Short-term intensive BW loss (≥5% of initial BW) increased NGR probability in all Pre-DM phenotypes, with an order of iIGT > combined IFG-IGT > iIFG. Only iIGT takes advantage of moderate BW loss (<5% of initial BW) to increase the chance of Pre-DM regression.

Associations between Global Diet Quality Score and Risk of Metabolic Syndrome and Its Components: Tehran Lipid and Glucose Study.

Background: Various food quality indicators have been proposed as tools for predicting metabolic syndrome (MetS). This study investigated the association between global diet quality score (GDQS) and the risks of developing MetS and its components. Methods: In this secondary analysis, we included elective adult participants (n=4,548) from the Tehran Lipid and Glucose Study. Dietary data were collected by a valid and reliable semi-quantitative food frequency questionnaire. MetS was defined according to the Iranian modified National Cholesterol Education Program. Multivariable Cox proportional hazard regression models were used to estimate the incidence of MetS in association with GDQS. Results: This study involved 1,762 men and 2,786 women with a mean±standard deviation age of 38.6±14.3 and 35.9±11.8 years, respectively. A total of 1,279 subjects developed MetS during the mean follow-up of 6.23 years. Incidence of MetS was associated with GDQS (hazard ratio [HR], 1.00; 0.90 [95% confidence interval, CI, 0.82 to 0.98]; 0.84 [95% CI, 0.76 to 0.91]; 0.80 [95% CI, 0.73 to 0.89]; P for trend <0.001) after adjusting for confounding variables. The healthy food group component of GDQS was related to MetS incidence. GDQS in the range of 12%-17% in the fourth quartile was associated with a decrease in incidence of MetS components. Both healthy and unhealthy food group components of the GDQS decreased the incidence of high triglycerides, high blood pressure, and high fasting blood glucose. Conclusion: Higher GDQS was associated with a lower risk of the incidence of MetS or its components among Tehranian adults. Higher intake of healthy food group components and lower consumption of unhealthy food group components of the GDQS predicted lower MetS incidence and risk factors.

Thyroid Hormone Replacement Dosing after Bariatric Surgery in Patients with Primary Hypothyroidism And Severe Obesity: Tehran Obesity Treatment Study.

Background: Obesity and hypothyroidism are common medical conditions that are associated with each other. Bariatric surgery (BS) is a common approach used to achieve substantial weight loss in obese patients. However, there is limited evidence regarding the need for postsurgery levothyroxine (LT4) dose adjustment in patients with hypothyroidism undergoing BS. Methods: This was a three-year prospective cohort study assessing postsurgery LT4 requirements with attention to body composition changes. The current study included 1030 patients with hypothyroidism, who underwent sleeve gastrectomy (SG) (n = 707, 88.3% women) or one anastomosis gastric bypass (OAGB) (n = 323, 92% women). Patients were followed for 36 months after surgery. A bioelectrical impedance analyzer was used for body composition assessment. LT4 requirements were assessed by generalized estimating equation (GEE) methods adjusted for weight as a time-varying covariate. Results: During the follow-up, TSH (mIU/L) and T4 (ng/dL) measurements did not significantly change in the OAGB group over time. However, in the SG group, TSH measurement decreased over time (ptrend = <0.001). In the third year of the follow-up, 56.1% and 33.3% of patients in the SG and OAGB groups experienced LT4 (µg/day) dose reduction, while 24.4% and 9.1% of the participants experienced LT4 dose increments, respectively. GEE analysis showed a significant increase in the LT4/fat mass (FM) (µg/kg) ratio after 36 months of follow-up compared with the baseline in both the SG [1.8 (1.5-2.2) to 2.7 (2.0-3.5), ptrend = 0.039)] and OAGB [1.7 (1.4-2.2) to 3.2 (2.7-4.8), ptrend = <0.001)] groups. Moreover, patients who underwent OAGB experienced greater LT4/FM (µg/kg) dose adjustments compared to those undergoing SG (pbetween = 0.060). In both groups, after the first year, the increase in LT4/FM (µg/kg) plateaued (pinteraction = 0.009). Conclusion: Most hypothyroid patients experienced either a reduction or no change in LT4 (µg/day) dosage after 36 months in both surgical groups. The LT4/FM (µg/kg) was significantly increased in patients undergoing either SG or OAGB with greater alterations in the latter. Further studies on larger populations and with longer duration of follow-up are needed to confirm our results.

Consumption of ultra-processed foods and the incidence of hypertension: a cohort study.

The incidence of hypertension (HTN) and consumption of ultra-processed foods are increasing worldwide. However, only a limited amount of research has assessed the causality between ultra-processed foods and the risk of HTN. Therefore, the present study aimed to determine the association between ultra-processed foods and the risk of HTN in a prospective cohort study. In the present study, we included 2399 individuals, aged approximately 19 years, who participated in the Tehran Lipid and Glucose Study (TLGS). The participants had complete dietary data and were free from HTN at baseline. We used the Cox proportional hazards model to determine the association between ultra-processed food intake and the risk of HTN occurrence, reporting the results as the hazard ratio (HR) and 95% confidence interval (95% CI). The mean age of participants was 37.6 years, and we followed them up for an average of 9.21 years. Our results indicated that participants in the highest tertile of ultra-processed foods had a 48% higher risk of HTN development (HR: 1.48; 95% CI: 1.23, 1.79) than those in the lowest tertile. We found a significant association between age and ultra-processed food intake in relation to the risk of HTN. The HR for developing HTN in participants aged <47 years was 1.99 (95% CI: 1.53, 2.58) and in participants aged ≥47 years was 1.26 (95% CI: 0.95, 1.68). Among the ultra-processed food components, consumption of industrial fat products had a positive correlation with the risk of HTN (HR: 1.04; 95% CI: 1.02 to 1.06). Our results suggest that consuming ultra-processed foods is associated with an increased incidence of HTN in adults. This association varied by age and was significant for adults younger than 47 years.

Fruit and vegetable intake modifies the association between ultra-processed food and metabolic syndrome.

BACKGROUND: This prospective cohort study aimed to investigate the association between ultra-processed food (UPF) and the risk of metabolic syndrome (MetS), as well as to assess whether fruit and vegetable intake and weight change modify this association. METHODS: We included 1915 healthy participants who participated in the Tehran Lipid and Glucose Study (TLGS), all of whom had complete demographic, anthropometric, and dietary measurements. A validated food frequency questionnaire was used to assess UPF consumption based on the NOVA classification system. MetS was defined according to the Joint Interim Statement. Multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) for MetS events across tertiles of UPF. The effect of fruit and vegetable consumption and weight change on this association was assessed using joint classification by Cox regression. RESULTS: UFP consumption showed no association with MetS risk after adjusting for confounders. However, after adjustment for dietary fiber, fruits, and vegetables, the highest tertile of UPF consumption was positively linked to MetS risk, compared to the lowest tertile. There was a significant interaction between fruit, vegetable, and dietary fiber intake and UPF consumption concerning the risk of MetS (All P values < 0.05). Among individuals consuming less than 248 g/day of fruit, the risk of MetS increased by 54% (confidence interval: 1.13-2.10) in the highest UPF tertile. Consuming vegetables and dietary fiber below the median (258 g/day and 42.2 g/day, respectively) increased the risk of MetS in the third tertile of UPF. However, consuming vegetables and fiber ≥ median intake, reduced the risk of MetS among those with the lowest UPF consumption. Furthermore, the risk of MetS was observed in the third tertile of UPF consumption among individuals with fruit and vegetable consumption < 537 g/day. UPF consumption was not associated with the risk of MetS in different weight change statuses. CONCLUSIONS: Consuming more fruits and vegetables mitigated the adverse effect of UPF on the risk of developing MetS.

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

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

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.

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

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

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

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

Approach to the Patient Considering Long-term Antithyroid Drug Therapy for Graves' Disease.

Antithyroid drugs (ATD) are the treatment of choice for the majority of patients with Graves' hyperthyroidism worldwide. However, relapse of hyperthyroidism after withdrawal of arbitrarily chosen conventional 12 to 18 months of therapy is very common. In the last 2 decades, many studies have shown that treatment with long-term ATD (LT-ATD) is effective and safe in the maintenance of euthyroidism. In addition, it has been reported that serum TSH receptor antibody may not decrease permanently before 5 to 6 years of ATD treatment, and clinical trials have shown that ≥5 years of ATD treatment is accompanied by remission in the majority of patients with Graves' hyperthyroidism. The objective of this article is to discuss the optimal time to withdraw of conventional ATD therapy, to illustrate the decision-making of the management of recurrent hyperthyroidism, to review the proper management of LT-ATD, and to generate suggestions for lifelong ATD treatment by discussing 4 scenarios of decision-making in patients with Graves' disease.

Herbal Products as Complementary or Alternative Medicine for the Management of Hyperglycemia and Dyslipidemia in Patients with Type 2 Diabetes: Current Evidence Based on Findings of Interventional Studies.

Type 2 diabetes (T2D) is known as a major public health problem with a noticeable adverse impact on quality of life and health expenditures worldwide. Despite using routine multiple pharmacological and nonpharmacological interventions, including diet therapy and increasing physical activity, controlling this chronic disease remains a challenging issue, and therapeutic goals are often not achieved. Therefore, recently, other therapeutic procedures, such as using herbal products and functional foods as complementary or alternative medicine (CAM), have received great attention as a new approach to managing T2D complications, according to the literature. We reviewed the existing evidence that supports using various fundamental medicinal herbs, including cinnamon, saffron, ginger, jujube, turmeric, and barberry, as CAM adjunctive therapeutic strategies for T2D patients. The current review addressed different aspects of the potential impact of the abovementioned herbal products in improving glycemic indices and lipid profiles, including the effect size reported in the studies, their effective dose, possible side effects, herbs-drug interactions, and their potential action mechanisms.

Association of Dietary Polyphenol Intakes with Metabolic Syndrome and its Components: Tehran Lipid and Glucose Study.

BACKGROUND: This study was conducted to assess the prospective association between dietary polyphenols intakes and risk of metabolic syndrome (MetS) and its components. METHODS: Participants in this study (n=4559) were selected from among the adults of the Tehran Lipid and Glucose Study (TLGS) with an average follow-up of 5.9+2.5 years. Biochemical and anthropometric variables were measured at baseline and follow-up examinations. A reliable and valid semi-quantitative food frequency questionnaire was used to evaluate dietary intakes. The incidence of MetS and its components in relation to polyphenols and its subclasses (phenolic acids, flavonoids, lignans, and stilbenes) was evaluated using multivariable Cox proportional hazard regression models. RESULTS: Of the 4559 subjects who enrolled in the present study, 1765 were male aged 38.6+14.2 y and 2794 were female aged 35.9+11.7 y. The hazard ratios of MetS were 25% lower in Q2 (HR, 95% CI: 0.75, 0.64‒0.88), 22% lower in Q3 (HR, 95% CI: 0.78, 0.65‒0.94) and 24% lower in Q4 (HR, 95% CI: 0.76, 0.61‒0.95) in comparison to Q1, whereas the results for subclasses of polyphenol were non-significant. The risk of high blood pressure (BP) reduced from quartiles 1 to 4 for phenolic acid (HR: 1.00, 0.88, 0.79, 0.80, Ptrend=0.03). The risk of low high-density lipoprotein cholesterol (HDL-C) increased across quartiles of phenolic acid (HR: 1.00, 1.22, 1.07, 1.30, Ptrend=0.02). CONCLUSION: This study highlights the potential protective role of total dietary polyphenols in the prevention of MetS. These findings could be the starting point of upcoming trials to illuminate the optimal level of polyphenols deriving from the intake of polyphenol-rich diets to prevent MetS.