International Journal of Endocrinology and Metabolism
Volume:16 Issue: 4, Oct 2018

In the late 1990s the non-communicable diseases were becoming increasingly more prevalent and a significant proportion of evidence in this regard had originated from industrialized “Western” countries. This had led to a landscape where most national and local health decisions regarding non-communicable diseases (NCDs) were informed by data generated elsewhere. Iran, as a large country in the Middle East was no exception and was going through significant population growth and urban development at the time. An initiative by the Iranian National Scientific Research Council funded an idea that was aimed at delineating the local epidemiology of NCDs and their risk factors in a manner that was unprecedented. The result was Tehran Lipid and Glucose Study (TLGS), the first and longest running cohort of its sort in Iran. Initial data out of TLGS reported the characteristics of 15005 people aged over 3 years in a representative population of Tehranians. Additionally, distribution and prevalence of cardiovascular risk factors among the study population were characterized. This population was selected through a multistage stratified cluster random sampling technique from the population of district 13 in Tehran. In addition, TLGS gave rise to a great deal of important and highly effective initial findings on national cut-off points for various variables, information about nutrition, hypertension, dyslipoproteinemia, and metabolic syndrome. TLGS also generated information about metabolic health indicators among children and adolescents. Here we present a brief overview of rationale, design, and initial findings of TLGS.

Context: The high prevalence of chronic diseases can be prevented or managed by specific changes in lifestyle patterns of individuals of which dietary factors is emphasized. The objective of this study was to review all findings of the Tehran Lipid and Glucose Study regarding validity and reliability of food frequency questionnaire (FFQ), evaluating dietary quality and association of dietary factors in relation to diabetes, dysglycemia, cardiovascular (CVD) and chronic kidney disease (CKD). Evidence Acquisition: Related documents were searched through PubMed and Scopus databases, in English language from 2000 to 2017. Finally, 52 relevant documents were eligible for inclusion in this review. The FFQ proved to be an acceptable tool for assessing nutrient and food group intakes and rank individuals accurately according to the levels of their dietary intakes. After 8 years of follow-up, the western dietary pattern (DP) was fairly stable but there was instability of traditional Iranian DP. DPs of over two-thirds of Tehranian populations were not in accordance with the dietary recommendations. Higher dietary scores of variety and healthy DPs were also associated with reduced odds of dysglycemia. The main dietary factor related to increased risk of CVD in our population was western DP. Patterns of amino acid intakes may contribute to the development of CVD. Higher intakes of several micronutrients and macronutrients, DPs and some vegetables decrease the risk of CKD. In conclusion DPs of most Tehranian adults need improvement. This review showed that higher adherence to healthy food choices was associated with reduced odds of dysglycemia and CVD. Dietary sources of renal-protective nutrients should be encouraged among the general population.

Context: Genetic and environmental factors contribute to the incidence of metabolic syndrome (MetS). This study aimed to review all findings of studies conducted in framework of the Tehran lipid and glucose study (TLGS) regarding the association of dietary factors with cardio-metabolic risk factors. Evidence Acquisition: All English-language studies were searched using PubMed and Scopus databases from 2000 to 2017. Finally, 105 relevant papers were included in this review. Whole grains, legumes, nuts and healthy dietary patterns (DPs) reduced risk of MetS, while white rice, salty/sweet snacks increased this. The western DP had a significant interaction with APOC3, APOA1 and MC4R polymorphisms in relation to MetS. After 6.5 years of follow-up, odds of reaching menarche ≤ 12 years was significantly higher in girls with higher intakes of milk, calcium, magnesium, and phosphorous. Among children and adolescents, higher adherence to the dietary approaches to stop hypertension (DASH)-style diet decreased the risk of abdominal obesity, whereas increased adherence to the western DP could contribute to general and abdominal obesity. A three-year follow-up of adult participants showed that higher intakes of phytochemical-rich foods were inversely related to development of insulin resistance. Higher adherence to the healthy DPs was associated with the reduced risk of hyperlipidemia and hypertention. Nutrition interventions postponed rise in the prevalence of MetS. The DASH diet resulted in weight reduction compared to control diet. Higher adherence to healthy food choices was associated with reduced odds of MetS, abdominal obesity, dyslipidemia and hypertension. The western DP accentuated the association of polymorphisms with MetS.

Context: Low physical activity is one of the major risk factors for non-communicable diseases (NCD) such as cardiovascular disease and type 2 diabetes. The current paper reviews the main findings from Tehran lipid and glucose study (TLGS) that focus on physical activity and its association with cardiometabolic risk factors over the past two decades. Evidence Acquisition: We conducted a literature search for articles from 1999 to December 2017 using the search terms: (Physical activity, leisure time physical activity, non-communicable disease, and TLGS). The prevalence of low physical activity was 69.8% during phase ΙΙ of TLGS (2000 - 2004). During 6.5 years of follow up, the prevalence of low physical activity in the total population decreased significantly between phases II (2000 - 2004) and IV of TLGS (2008 - 2010) (P < 0.05). Overweight individuals with sedentary lifestyles had a higher risk of metabolic syndrome, compared to those who had high levels of leisure-time physical activity in phase IV of TLGS (2008 - 2010); in the obese group, systolic blood pressure, and triglyceride levels differed significantly between different leisure-time physical activity categories (106.9 ± 14.3 vs. 119.1 ± 17.2 mmHg, P = 0.03) and (111.4 ± 1.6 vs. 147.1 ± 1.6 mg/dL, P = 0.01), respectively. The present review highlights the impact of low physical activity on the health of the TLGS community from adolescence to adulthood. The decreased prevalence of low physical activity from phase ΙΙ to phase ΙV of TLGS indicates the necessity for lifestyle interventions as a potentially effective strategy, which could have a positive impact on various risk factors and indicators of non-communicable diseases such as body mass index, waist circumference, systolic blood pressure, and lipid profiles.

Context: Smoking is a global public health priority and accurate data of the local population is essential to improve the health policies against its use. Hence, this study aimed to summarize the important findings available on the prevalence of smoking and its association with non-communicable diseases, documented by one of the largest prospective community-based studies of Iran. Evidence Acquisition: All articles derived from the Tehran Lipid and Glucose Study (TLGS) in the last two decades, from the earliest publications until 30 January 2018 were reviewed for their findings on tobacco smoking. The prevalence of smoking in non-diabetic adults ≥ 20 years increased between baseline (phase I, 1999 - 2001) and follow-up (phase V, 2008 - 2011) from 25.5% to 35.4% among men and from 3.4% to 6.8% among women. In TLGS adolescents (10 - 18 years) water pipe use increased between 2003 and 2005 from 35.5% to 40.9% among boys and from 19.7% to 26.1% among girls. Regarding health hazards, smoking in men was associated with increased risk of combined impaired fasting glucose/impaired glucose tolerance [hazard ratio (HR) 1.69; confidence interval (CI) 95% 1.15 - 2.48] and hypertension (HR 1.26; CI 95% 0.98 - 1.63). Moreover, men, even smoking less than 10 cigarettes per day, were at increased risk for cardiovascular diseases by HR 2.12 (CI 95% 1.14 - 3.95). For women, the risk of chronic kidney disease dramatically increased 5.74-fold (CI 95% 2.71 - 12.15) among smokers. In the whole population, smoking contributed to 7.7% of all-cause mortality with HR 1.75 (CI 95% 1.38 - 2.22). Other health aspects of tobacco smoke, including its impact on metabolic status, thyroid function, female reproductive system and life style have also been reviewed. Considering hazards of smoking, there is the urgency for more effective preventive measures in Iran; emphasizing the need for further local studies on the hazards of smoking with special attention to women and adolescents and the independent hazards of water pipe use.

Context: The Tehran Lipid and Glucose Study (TLGS) is a community-based study to reveal the frequency of non-communicable diseases (NCDs) in Tehran's population. This research consists of two main parts, a cross-sectional study on the prevalence of cardiovascular risk factors and a 20-year-ongoing prospective cohort study, which was initiated in 1999 in several phases with an approximate duration of 3.6 years, and is still ongoing. The aim of the present study is review the 20 year biochemical findings of the TLGS related to the NCDs in a large sample. All articles on biochemical assessments derived from the TLGS from the earliest publications (2002) until 30 January 2018 were reviewed for their findings on different risk factors of NCDs. According to the TLGS findings high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), homocysteine (Hcy), age, smoking, hypertension, and obesity were the most important risk factors of cardiovascular diseases (CVD). It was illustrated that in subjects with abdominal obesity, the hs-CRP and IL-6 serum levels were higher than in normal subjects. The most appropriate prognostic indexes and associations were for hs-CRP, IL-6, and Hcy with abdominal obesity, waist circumference, WHtR, and wrist circumference, respectively. Previous studies have demonstrated a direct relationship between obesity and serum levels of inflammatory factors. According to the results of TLGS, serum levels of biochemical risk factors such as hs-CRP, IL-6, and Hcy could be beneficial in early diagnosis and effective treatment of cardiovascular, obesity and other metabolic diseases.

Context: We summarized findings from Tehran lipid and glucose study (TLGS) about different aspects of type 2 diabetes (T2D) over the span of nearly 2 decades. Evidence Acquisition: A review was undertaken to retrieve papers related to all aspects of T2D from the earliest date available up to January 30, 2018. An annual crude incidence rate of 10 per 1000 person-years of follow-up was found for T2D in adult participants. Overall incidence rate of pre-diabetes/T2D was 36.3 per 1000 person-years or about 1% each year among youth. Diabetes was associated with increased risk of CVD [hazard ratio (HR): 1.86, 95% confidence interval (95% CI): 1.57 - 2.27] and mortality [HR: 2.56; 95% CI: 2.08 - 3.16] in the total population. Compared with non-diabetic men and women, their diabetic counterparts survived 1.4 and 0.7 years shorter, respectively, during 15 years of follow-up. Wrist circumference, hyperinsulinaemia, 25-hydroxy vitamin D and increase in alanin aminotranferase provided incremental prognostic information beyond the traditional risk factors for incident T2D in adults. Using decision tree algorithms, a number of high risk groups were found for incident T2D. A probability of 84% was found for incidence of T2D among a group of men with fasting plasma glucose (FPG) > 5.3 mmol/L and waist to height ratio (WHtR) > 0.56, and women with FPG > 5.2 mmol/L and WHtR > 0.56. Original TLGS studies have contributed greatly to clarify important evidence regarding the epidemiology and risk factors for T2D among Iranian population.

Context: The prevalence of overweight and obesity are increasing worldwide and have frequently been associated with health risks. This review highlighted several studies regarding obesity, outlining contributions of over a span of almost two decades in the Tehran Lipid and Glucose Study (TLGS). Evidence Acquisition: A systematic review was undertaken to retrieve articles related to all aspects of obesity from the earliest available date up to January 30, 2017. Prevalence of excess weight, including overweight and obesity were 20.8 and 63.6% among those aged below and above 20 years, respectively. TLGS found a high incidence of obesity with higher incidence in women among Tehranian adults; the cumulative incidence of obesity was 31.3, 38.1 and 23.4% for the whole population, women, and men, respectively. In children and adolescents, younger non-obese 7 - 9 years old, compared to 10 - 11 year olds are at greater risk of obesity. Prevalences of abdominal obesity in men and women were 52.8% and 44.4% respectively. Similar to generalized obesity, a high incidence of abdominal obesity was observed; the total cumulative incidence of abdominal obesity was 76.0% (83.6% for men and 70.9% for women). Metabolically healthy obese (MHO) and metabolically healthy abdominal obese (MHAO) are two important obesity phenotypes. People with these phenotypes have different risks for cardiovascular disease (CVD), type 2 diabetes (T2DM), and mortality. In the TLGS participants, MHO was found in 2% and 7.7% of the whole and obese population, respectively, whereas MHAO phenotype was reported in 12.4% and 23.5% of the whole and abdominal obese population. In these unstable conditions, during the long term follow up the metabolic risks developed in nearly half of the individuals. During a 12-year follow-up, incident CVD did not increase in the MHO phenotype compared to metabolically healthy normal weight (MHNW) individuals, but the risk of CVD events had increased in all metabolically unhealthy phenotypes. However in another report, over a 10-year follow-up, MHAO phenotype had an increased risk for CVD in comparison to the reference group, metabolically healthy non-abdominal obese (MHNAO) individuals. The TLGS studies bridged the significant gap in knowledge regarding prevalence, incidence, trends, morbidities and mortalities for obesity among Iranian population.

Context: Dyslipidemia, including elevated serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG), and low high density lipoprotein cholesterol (HDL-C) is a major modifiable risk factor for non-communicable diseases (NCDs). This review summarizes many of the key findings on lipid measures in the Tehran lipid and glucose study (TLGS), a large scale community-based study with an approximately two decade follow-up. Evidence Acquisition: A systematic literature search was conducted using PubMed, Scopus, Web of Science databases, and the library of the Research Institute for Endocrine Sciences, using the following keywords: Lipid measures, lipid ratios, lipid profile, dyslipidemia, and “Tehran lipid and glucose study”. Articles were categorized based on fields of prevalence, trends, and impact of lipid profile on incident NCDs and mortality. Between 1999 - 2001, the prevalence of high risk lipids ranged from 14% (low HDL-C) to 17% (high LDL-C) among adolescents, although among adults the lowest and highest prevalence were observed for low HDL-C (19%) and high TG (28%). Despite favorable trends for lipid parameters among adolescents, adults, and the elderly population, a considerable number of diabetic individuals, failed to achieve the optimum level of serum lipids. During follow-up, consumption of lipid-lowering drugs increased from 1.5 to 9.0% and 3.7 to 11.4% among adult men and women, respectively. The association between different lipid parameters and related ratios for incident type 2 diabetes (T2D), hypertension, metabolic syndrome and cardiovascular diseases differed between genders. Interestingly, each 1-unit increase in TC/HDL-C increased risk of hypertension among women (odds ratio (OR): 1.19, 95% confidence interval (CI): 1.00 - 1.27) and T2D among men (OR: 1.27, 95% CI: 1.06 - 1.51). Moreover, TC, LDL-C, non-HDL-C, Ln-TG, TC/HDL-C, and Ln-TG/HDL were inversely associated with non-cardiovascular mortality. Despite high prevalence of high risk lipid profiles among the TLGS population at baseline, favorable trends were observed in levels of all lipid components, which might be attributable to increased consumption of lipid-lowering medications and improvement in the general knowledge of Iranians regarding limited consumption of hydrogenated oil. Considering the impact of lipid profiles on incident NCDs, more attention should be paid to at-risk groups for screening and treatment purposes.

Context: Hypertension (HTN) is a well-known modifiable risk factor for cardiovascular disease (CVD), chronic kidney disease and mortality. Positive effects of blood pressure (BP) lowering for prevention of CVD and death have been documented in several meta-analyses of randomized controlled trials. Evidence Acquisition: This review focuses on the key findings derived from the Tehran lipid and glucose study (TLGS) papers on different aspects of BP and HTN. A prevalence of 23% for HTN has been reported in the TLGS population, aged ≥ 20 years. Over a decade long follow-up, the crude incidence rate (95% CI) of new-onset HTN defined as systolic BP (SBP) ≥ 140 mmHg and/or diastolic BP (DBP) ≥ 90 mmHg, and not using antihypertensive medication was 33.63 (32.0 - 35.3) per 1000 person-years. Age, baseline SBP and body mass index were significant risk factors for development of isolated systolic HTN; regarding isolated diastolic HTN, baseline DBP and waist circumference were recognized as important risk factors whereas age, female gender and marriage were shown to be protective factors. SBP decreased significantly in both diabetic and non-diabetic participants; DBP showed a non-significant decrease in diabetic men and a statistically significant decrease in non-diabetic men. Among women, both those with and without diabetes (DM) generally experienced statistically significant decreases in DBP. Cox proportional hazard models showed that neither SBP nor DBP were associated with incident DM in the total population and in either gender, separately. All BP components were associated with CVD and all-cause mortality in the middle-aged population. Contribution of HTN to cerebrovascular events was also documented in the TLGS participants, aged ≥ 50 years. Several important findings regarding BP/HTN have been derived from the TLGS. According to data regarding the prevalence and incidence of preHTN and HTN and their contribution to cardiovascular morbidity and mortality in the TLGS population as a representative sample of Tehranian population, it is recommended that interventions be prioritized for lifestyle modifications for the prevention and appropriate management of preHTN/HTN.

Context: In recent decades, investigations have been focused on the definition, incidence and predictors of metabolic syndrome (MetS) in Iranians. This study aimed to review systematically investigations on MetS, conducted among the Tehran lipid and glucose study (TLGS) participants. Evidence Acquisition: Literature on MetS documented by TLGS studies published from 2000 to 2017 were searched using Pubmed and Scopus database in English language with a combination of following keywords: Metabolic syndrome, TLGS. The harmonized definition of MetS was confirmed, based on the estimated cut point of waist circumference (WC) ≥ 95 cm for both genders in Iran. The incidence rate was 550.9/10000 person/years, lower among women (433.5/10000) than men (749.2/10000). The prevalence of abdominal obesity, high triglycerides (TG), low high density lipoprotein cholesterol (HDL-C), high blood pressure (BP), and high fasting blood glucose (FBG) was 30, 46, 69, 34, and 12%, respectively. The prevalence of MetS in adolescents was 10.1% with no significant difference between boys and girls (10.3% in boys and 9.9% in girls). A strong association of WC (OR: 2.32, CI: 2.06 - 2.59) and TGs (OR: 1.95, CI: 1.65 - 2.11) with development of MetS was found. In adolescent boys, WC had the highest OR for MetS risk. WHO-defined MetS was a significant predictor of total and cardiovascular mortality both in men (HR: 1.66, CI: 1.23 - 2.24; HR:1.93, CI: 1.26 - 2.94) and women (HR: 2.01, CI: 1.39 - 2.88; HR:2.71, CI: 1.44 - 5.09). Our results indicate high incidence of MetS in Tehranian adults and adolescents; high WC also appears to be a strong predictor of MetS. All definitions of MetS predicted cardiovascular disease.

Context: Chronic kidney disease (CKD), is correlated with a substantial upsurge in mortality and morbidity worldwide. In this review, we aimed to review the 20-year-findings on CKD of the Tehran lipid and glucose study (TLGS). Evidence Acquisition: We conducted a systematic review of all studies on CKD that had been performed in the context of TLGS. Age adjusted prevalence of CKD, according to estimated glomerular filtration rate (eGFR) assessed with the two abbreviated equations of the modification of diet in renal disease (MDRD) and the CKD epidemiology collaboration (CKD-EPI) were 11.3% (95% confidence interval (CI): 10.7, 12.0) and 8.5% (95% CI: 7.9, 9.1), respectively. Using MDRD equation, over a mean follow up of 9.9 years, the incidence density rates of CKD were 285.3 person years in women and 132.6 per 10000 person-years in men. Studies on the TLGS population documented that abdominal adiposity defined as waist circumference (WC) categories (P for trend < 0.02) and waist gain in men (hazard ratio (HR) = 1.7, CI: 1.3, 2.2) significantly affected CKD development. Also, CKD had a significant effect on coronary heart disease (CHD) only in participants with low body mass index (HR = 2.06; CI: 1.28, 3.31 and HR = 2.56; CI: 1.04, 6.31 in men and women, respectively). Moreover, CKD was among the strongest independent predictors of stroke (HR = 2.01, CI: 1.22, 3.33). Also, compared to diabetic patients, an abnormal ECG was more prevalent in moderate CKD (P = 0.02). Increased waist circumference and waist gain (only in men) were associated with developing CKD in the TLGS population. CKD was an independent predictor of CHD (in lean individuals) and stroke.

Context: Tehran Lipid and Glucose Study (TLGS), a longitudinal family based cohort study, is the oldest and largest longitudinal family based study in Iran, aimed at investigating effects of environmental, social and biological factors on the health of Tehranians over time. Considering the importance of genetic studies in this aspect, here we present a summary of the important genetic findings, and the potentiality of their contributions to future related projects. Evidence Acquisition: For all related studies during the past 20 years the search sources were all prominent search engines such as PubMed, Scopus, and Google Scholar with the most proper Medical Subject Headings (MeSH). This review summarizes associations of 6 binary phenotypes and 17 quantitative traits with genetic markers in 26 genes. Of the 47 genetic markers, studied most were related to cardio metabolic risk factors. Results of heritability and linkage analysis were also collected and the highest heritability was found to be related to HDL-C (0.5). Considering the opportunity provided by large-scale cohort studies to investigate molecular effects of genetic variants on causality and different omics’ data, genetic studies conducted on TLGS population have had a remarkable success in identifying genetic variants that facilitating a unique genetic database on Iranian populations. The results of genome wide association studies in this population are currently facilitating investigations to define the Iranian genetic differences with other population.

Context: Beyond the objective outcomes of metabolic syndrome (MetS), the association between this syndrome and its patient-centered outcomes need to be investigated in Middle-Eastern countries. This report aims to summarize the Tehran lipid and glucose study (TLGS) findings regarding the association between MetS and health-related quality of life (HRQoL) and its influential factors through the past decade. Evidence Acquisition: The current review has been conducted on the TLGS published data regarding different aspects of the association between MetS and HRQoL in adult participants through the last decade. To assess HRQoL, the Iranian version of short form health survey (SF-36) was used. To define MetS the most commonly used insulin resistance (IR)-and waist circumference (WC) - based MetS definitions have been applied in the publications reviewed. As a whole, MetS was a determinant of poor physical HRQoL only in women (OR: 1.78; 95% CI: 1.21 - 2.61), particularly in those with more component of MetS (P < 0.001). Results further showed that only reproductive aged women with MetS were more likely to report poor PCS compared to those without MetS even after adjusting for age (OR: 1.7, 95% CI: 1.0 - 3.0; P < 0.05). Different structures of MetS and physical HRQoL constructs in men and women as well as age and smoking with significant gender-specific effects on mental HRQoL were factors responsible for the gender specific pattern observed. Considering the duration of MetS, only women with intermittent MetS indicated higher risk for reporting poor PCS (OR: 2.75, 95% CI: 1.19 - 6.37; P < 0.001) compared to those without MetS. The observed sex-specific pattern used to detect poor HRQoL in those with MetS was confirmed by all WC-based definitions except for the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) definition. However, none of IR-based definitions could detect poor physical and mental HRQoL in either gender. In summary, in the TLGS population, the association between MetS and HRQoL followed a sex specific pattern, mainly significant only in women and in the physical aspect.

Context: We describe here the contributions of the Tehran lipid and glucose study (TLGS) to understanding different aspects of the nitrate (NO3)-nitrite (NO2)-nitric oxide (NO) pathway in health and disease. Evidence Acquisition: All English-language documents from the TLGS, focused on NO pathway were searched using the PubMed, Scopus, and Embase databases. Reference values of serum concentrations of NO metabolites (nitrate+nitrite or NOx) were 11.5 - 76.4, 10.1 - 65.6, and 10.3 - 66.8 μmol/L in men, women, and the total population, respectively. Circulating NOx was affected by age, smoking habits, menopause status, thyroid hormones, and various pathologic conditions. Elevated serum NOx was related to increased incidence of metabolic syndrome (odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.19 - 2.59), hypertriglyceridemic-waist phenotype (OR = 1.39, 95% CI = 1.05 - 1.93), chronic kidney disease (OR = 1.86, 95% CI = 1.10 - 3.14) in women, and cardiovascular disease (hazard ratio (HR) = 1.35, 95% CI = 1.01 - 1.80] in the total population. In participants with low vitamin C intake, higher intakes of NO2 (≥ 8.77 mg/d) were accompanied with increased risk of diabetes (HR = 2.43, 95% CI = 1.45 - 4.05). A decreased risk of hypertension (OR = 0.58, 95% CI = 0.33 - 0.98) and chronic kidney disease (OR = 0.50, 95% CI = 0.24 - 0.89) was observed in response to higher intakes of NO2. Circulating NOx is associated with and could predict the risk of metabolic disorders in a general population. Moreover, dietary NO3/NO2 exposure from usual diets seems to contribute to development of noncommunicable diseases.

Context: The Tehran lipid and glucose study (TLGS) is one of the oldest population-based longitudinal cohort studies, providing knowledge about the incidence and risk factors of some non-communicable diseases (NCDs) in West Asia which hitherto was relatively scarce. We reviewed the methods and results related to the outcome measurements of this study. Evidence Acquisition: We reviewed all the TLGS papers which reported the incidence of NCDs. The TLGS was initiated in 1999 - 2001 on a population in district no. 13 of Tehran with the same age distribution of the overall Tehran population and with a middle socioeconomic status. Totally, 15005 individuals, aged ≥ 3 years, participated in the first examination; reexaminations were conducted in a triennial manner and 3550 individuals were added in the second examination. All participants were also followed up annually and asked about any medical event leading to hospitalization or death. A part of participants was assigned to an educational program for lifestyle modification. High incidence of cardiovascular disease (CVD), premature CVD, diabetes and hypertension (around 19, 6, 10 and 31 in men and 11, 5, 11 and 29 in women per 1000 person-year, respectively) besides the high incidence of pre-diabetes and pre-hypertension (around 46 and 76 in men and 37 and 49 in women per 1000 person-year, respectively) showed a worrying situation. Fortunately, the results of the community interventions were promising with around 20% reduction in the risk of metabolic syndrome up to six years. These precise detections of different outcomes in the TLGS provided valuable evidences for prediction and prevention of NCDs in Iran with some novelties in the middle-income countries in the world. The Tehran thyroid study (TTS) and the Tehran cardiometabolic genetic study (TCGS), conducted in the framework of the TLGS, are among few studies aiming to determine the natural course of thyroid function and to identify patterns of genetic polymorphisms related to cardiometabolic outcomes, respectively.

Context: This review summarizes key findings of the Tehran thyroid study (TTS), a large scale community-based study with approximately a two decade follow-up, about the incidence, prevalence, and natural course of thyroid disorders as well as associations between thyroid diseases and metabolic syndrome (MetS), dysglycemia, and cardiovascular disease (CVD). Evidence Acquisition: PubMed, Scopus, and Web of Science databases, and the library of Research Institute for Endocrine Sciences were used to search for TTS articles. Articles were subdivided based on the fields of prevalence, incidence and natural course, and associations of thyroid function with the incident hypertension (HTN), MetS and CVDs. The 2.5th and 97.5th percentiles of serum thyrotropin (TSH) were 0.32 and 5.06 mU/L, respectively. Estimated reference intervals (2.5th and 97.5th percentiles) for thyroid peroxidase antibody (TPOAb) levels were 1.5 - 32.8 and 2.1 - 35 IU/mL in men and women, respectively. Euthyroid persistency was 93.24% during 6 years. There was a negative association between free thyroxine (FT4) levels and insulin resistance. Decreasing FT4 values over time would predict MetS in euthyroid and subclinical hypothyroid subjects (TSH < 10 mU/L). The incidence of thyroid disorders in patients with diabetes, pre-diabetes and healthy controls was 14, 18, and 21 per 1000 person-years, respectively, indicating significantly lower incidence in individuals with diabetes compared to healthy controls. Serum FT4 within the reference range was positively associated with all blood pressure (BP) measures in the total population and in men; however, serum TSH was positively associated with only systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure of men. No associations were found between various states of thyroid function and prevalence and incidence of CVD. A well designed cohort study aimed to investigate the gap in knowledge regarding thyroid disorders can generate many hypotheses to be examined in randomized controlled trials.

Context: Reproductive domains of the Tehran lipid and glucose study (TLGS) are unique in that they provide reliable information on reproduction of an urban population of West Asia. The aim of this review is to present the most important reproductive findings of TLGS. Evidence Acquisition: This review is summarizing all articles published in the context of reproductive aspects of TLGS results over the 20-year follow-up. A comprehensive databases search was conducted in PubMed (including Medline), Web of Science and Scopus for retrieving articles on the reproductive histories in context of the TLGS. The mean (SD) age at menarche and menopause was 13 (1.2) and 49.6 (4.5) years respectively. While pills were the most commonly used modern methods at the initiation of TLGS, the prevalence of condoms rose sharply and significantly over the follow up duration. Among women with history of gestational diabetes, the risk of diabetes and dyslipidemia progression were 2.44 and 1.2 fold higher than others. Prevalences of PCOS and idiopathic hirsutism among reproductive age participants of TLGS were 8.5% (95% CI: 6.8% - 10.2%) and 13.0% (95% CI: 10.9% - 15.1%), respectively. Trend of cardio-metabolic risk factors among women with PCOS showed that there were no statistically significant differences between mean changes of each cardio metabolic variables between PCOS and healthy women; PCOS status also significantly associated with increased hazard of diabetes and prediabetes among women aged younger than 40 years (HR: 4.9; 95% CI: 2.5 - 9.3, P value < 0.001)) and (HR: 1.7; 95% CI: 1.1 - 2.6), P value < 0.005), respectively. The population based nature of TLGS provides a unique opportunity for valid assessment of reproductive issues, the results of which could provide new information for modification of existing guidelines.

Tehran Lipid and Glucose Study (TLGS), an epidemiological study of non-communicable disease with 20 years follow up in a developing country in nutrition transition is a unique study in 15000 family based individuals, 3 - 75 years of age in a part of large city of Tehran. The success rate of recruitment for 20 years, intervention for lifestyle change, and thyroid, reproduction and cardiometabolic genetic studies derived from TLGS have paved suitable path towards precision medicine. In this review, baseline findings and changes of risk factors for the development of NCD including body weight, nutrition, physical activity, blood pressure, tobacco smoking, serum glucose and serum lipids as well as metabolic syndrome, chronic kidney disease, quality of life and biochemical findings in TLGS cohort have been summarized. The results of community based intervention for lifestyle change caused decreases in the prevalence of metabolic syndrome and the incidence of diabetes. It is concluded that TLGS has served as a model for other cohort studies in Iran and the region; it has helped to mobilize scientists in developing countries; it has established locally needed definitions of NCD variables; has served as a model for cohort studies in developing countries in nutrition transition with all socioeconomic constraints and has helped manpower education and development of local CVD risk scores for implementation of NCD management.