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1.  Trends in Cardiovascular Disease Risk Factors in People with and without Diabetes Mellitus: A Middle Eastern Cohort Study 
PLoS ONE  2014;9(12):e112639.
Aims/Hypothesis
To investigate secular trends in cardiovascular disease (CVD) risk factors during a decade of follow-up in a Middle Eastern cohort, and to compare observed trends between diabetic and non-diabetic populations.
Methods
In a population of 6181 participants (2622 males and 3559 females), diabetes status and CVD risk factors were evaluated in 4 study phases from 1999–2011. 1045 subjects had type 2 diabetes mellitus at baseline and 5136 participants were diabetes-free. To examine the trends of CVD risk factors, generalized estimation equation models were constructed. The interaction between the diabetes status and each phase of the study was checked in a separate model.
Results
During the follow-up period diabetic females significantly gained better control of their blood pressure, serum low density lipoprotein cholesterol and general and central obesity measures compared to non-diabetic counterparts, although 60% of them had high BP and 64% had high serum LDL-C levels till the end of the study. Diabetic males however, experienced significantly better control on their serum LDL-C and general and central obesity measures compared to their non-diabetic controls; but 24% of them were still smoker, 63% had high BP and 60% had high serum LDL-C levels at the end of the follow-up (all Ps interaction <0.05). Use of lipid-lowering and antihypertensive medications increased consistently in both diabetic and non-diabetic populations.
Conclusions/Interpretation
Although CVD risk factors have been controlled to some extent among diabetic population in Iran, still high numbers of people with diabetes have uncontrolled CVD risk factors that prompt more attention.
doi:10.1371/journal.pone.0112639
PMCID: PMC4251920  PMID: 25461381
2.  Lipid Accumulation Product Is Associated with Insulin Resistance, Lipid Peroxidation, and Systemic Inflammation in Type 2 Diabetic Patients 
Endocrinology and Metabolism  2014;29(4):443-449.
Background
Lipid accumulation product (LAP) is a novel biomarker of central lipid accumulation related to risk of diabetes and cardiovascular disease. In this study, we assessed the association of LAP with glucose homeostasis, lipid and lipid peroxidation, and subclinical systemic inflammation in diabetic patients.
Methods
Thirty-nine male and 47 female type 2 diabetic patients were assessed for anthropometrics and biochemical measurements. LAP was calculated as [waist circumference (cm)-65]×[triglycerides (mmol/L)] in men, and [waist circumference (cm)-58]×[triglycerides (mmol/L)] in women. Associations of LAP with fasting glucose, insulin, insulin resistance index, lipid and lipoprotein levels, malondialdehyde, and high-sensitive C-reactive protein (hs-CRP) were assessed.
Results
Mean age and LAP index were 53.6±9.6 and 51.9±31.2 years, respectively. After adjustments for age, sex and body mass index status, a significant positive correlation was observed between LAP index and fasting glucose (r=0.39, P<0.001), and homeostasis model assessment of insulin resistance (r=0.31, P<0.05). After additional adjustment for fasting glucose levels, antidiabetic and antilipidemic drugs, the LAP index was also correlated to total cholesterol (r=0.45, P<0.001), high density lipoprotein cholesterol (HDL-C) levels (r=-0.29, P<0.05), triglycerides to HDL-C ratio (r=0.89, P<0.001), malondialdehyde (r=0.65, P<0.001), and hs-CRP levels (r=0.27, P<0.05).
Conclusion
Higher central lipid accumulation in diabetic patients was related to higher insulin resistance, oxidative stress and systemic inflammation.
doi:10.3803/EnM.2014.29.4.443
PMCID: PMC4285040  PMID: 25325262
Diabetes mellitus, type 2; Lipid accumulation product; Subclinical inflammation; Oxidative stress
3.  Epigenetic modifications in human thyroid cancer 
Biomedical Reports  2014;3(1):3-8.
Thyroid carcinoma is the most common endocrine malignancy of the endocrine organs, and its incidence rate has steadily increased over the last decade. Over 95% of thyroid carcinoma is derived from follicular cells that have a spectrum of differentiation to the most invasive malignancy. The molecular pathogenesis of thyroid cancer remains to be clarified, although activating the RET, RAS and BRAF oncogenes have been well characterized. Increasing evidence from previous studies demonstrates that acquired epigenetic abnormalities participating with genetic alteration results in altered patterns of gene expression/function. Aberrant DNA methylation has been established in the CpG regions and microRNAs (miRNAs) expression profile recognized in cancer development. In the present review, a literature review was performed using MEDLINE and PubMed with the terms ‘epigenetic patterns in thyroid cancer [or papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid cancer (MTC), anaplastic thyroid cancer (ATC)]’, ‘DNA methylation in thyroid cancer (or PTC, FTC, MTC, ATC)’, ‘miRNA expression in thyroid cancer (or PTC, FTC, MTC, ATC)’, ‘epigenetic patterns in cancer’ and the current understanding of epigenetic patterns in thyroid cancer was discussed.
doi:10.3892/br.2014.375
PMCID: PMC4251143  PMID: 25469237
epigenetic; DNA methylation; microRNA; thyroid cancer
4.  Is persistence of metabolic syndrome associated with poor health-related quality of life in non-diabetic Iranian adults? Tehran Lipid and Glucose Study 
Aims/Introduction
Previous research showed the association between health-related quality of life and metabolic syndrome (MetS). The present study aimed to examine the impact of persistence of MetS on health-related quality of life in non-diabetic Iranian adults.
Materials and Methods
This was a cross-sectional study. A representative sample of 643 non-diabetic individuals (67% female), aged ≥20 years, who participated in the Tehran Lipid and Glucose Study in 2005–2007 were recruited for the study, and categorized into four groups, those without, with transient, with intermittent and with persistent MetS. Health-related quality of life was assessed using the Iranian version of the Short Form Health Survey. MetS was diagnosed using the Joint Interim Statement criteria.
Results
Women with transient, intermittent and persistent MetS scored lower on the Physical Component Summary than those without the syndrome (51.03 ± 1.41, 48.16 ± 1.46 and 46.58 ± 1.29 vs 52.18 ± 1.20) after adjusting for potential confounders (P = 0.04). In women, there was also a significant decreasing trend in the scores of bodily pain (P for trend = 0.006) and general health (P for trend = 0.005) across the study groups. Compared with women without MetS, the odds ratio of reporting poor health-related quality of life for women with intermittent MetS was 2.75 (95% confidence interval 1.19–6.37, P = 0.01). Among men, however, no significant difference was observed in any of the health-related quality of life domains.
Conclusions
Compared with women without, with transient and with persistent MetS, those with intermittent MetS reported poorer physical health-related quality of life.
doi:10.1111/jdi.12222
PMCID: PMC4234232  PMID: 25422769
Metabolic syndrome; Persistency; Quality of life
5.  The prevalence of metabolic disorders in various phenotypes of polycystic ovary syndrome: a community based study in Southwest of Iran 
Background
Polycystic ovary syndrome (PCOS) is a common endocrinopathy, associated with metabolic abnormalities. Metabolic features of various phenotypes of this syndrome are still debatable. The aim of present study hence was to evaluate the metabolic and hormonal features of PCOS phenotypes in comparison to a group of healthy control.
Methods
A total of 646 reproductive-aged women were randomly selected using the stratified, multistage probability cluster sampling method. The subjects were divided into five phenotypes: A (oligo/anovulation + hyperandrogenism + polycystic ovaries), B (oligo/anovulation + hyperandrogenism), C (hyperandrogenism + polycystic ovaries) and D (oligo/anovulation + polycystic ovaries). Hormonal and metabolic profiles and the prevalence of metabolic syndrome among these groups were compared using ANCOVA adjusted for age and body mass index.
Results
Among women with PCOS (n = 85), those of groups A and C had higher serum levels of insulin and homeostatic model assessment for insulin%20resistance (HOMA-IR), compared to PCOS women of group D. Serum concentrations of cholesterol, low density lipoprotein, triglycerides and glucose in group A were higher than in other phenotypes, whereas the metabolic syndrome was more prevalent among group B.
Conclusions
Women who had all three components of the syndrome showed the highest level of metabolic disturbances indicating that metabolic screening of the severest phenotype of PCOS may be necessary.
Electronic supplementary material
The online version of this article (doi:10.1186/1477-7827-12-89) contains supplementary material, which is available to authorized users.
doi:10.1186/1477-7827-12-89
PMCID: PMC4180586  PMID: 25224635
PCOS; Metabolic disorders; Metabolic syndrome; Phenotype
6.  Main Facilitators of Smoking Among Young Males in Tehran: Tehran Lipid and Glucose Study 
Background:
Smoking is the most preventable risk factor for non-communicable diseases and its alarming trend.
Objectives:
The aim of this study was to explore and determine facilitating factors for smoking in young males, who participated in the Tehran Lipid and Glucose Study (TLGS), from their own perspective.
Patients and Methods:
This qualitative study was conducted within the framework of the TLGS. Participants were young males with 15 to 25 years of age and various levels of education. The inductive content analysis approach was used to analyze data on the participants’ perceptions with regard to smoking facilitators. Data collection was conducted through discussions by six semi-structured focus groups consisted of five to seven people. All the interviews were transcribed after being recorded and analyzed through constant comparative analysis.
Results:
Two main categories derived from the analysis of the data: I) personal needs and features; and II) environmental facilitators. The former concept included three subcategories: 1) fulfilling essential needs; 2) search for identity; and 3) lack of life skills. Environmental facilitators were also divided into two subcategories: 1) social patterns; and 2) ease of access.
Conclusions:
Tendency towards smoking is influenced by different factors. Clarifying these influential factors for smoking from the perspective of young males can be important in designing effective preventive programs.
doi:10.5812/ircmj.15429
PMCID: PMC4270672  PMID: 25593726
Qualitative Research; Smoking; Youth; Glucose
7.  The Incidence of Coronary Heart Disease and the Population Attributable Fraction of Its Risk Factors in Tehran: A 10-Year Population-Based Cohort Study 
PLoS ONE  2014;9(8):e105804.
Background
Data on incidence of coronary heart disease (CHD) is scarce in the Middle East and little is known about the contribution of known risk factors in this area.
Methods
The incidence of CHD and the effect of modifiable risk factors were explored in 2889 men and 3803 women aged 30–74 years in the population based cohort of the Tehran Lipid and Glucose Study, during 1999–2010. Average population attributable fraction (aPAF) was calculated for any risk factor using direct method based on regression model.
Results
The crude incidence rate in men was about twice that in women (11.9 vs. 6.5 per 1000 person-years). The aPAF of hypertension, diabetes, high total cholesterol and low-HDL cholesterol was 9.4%, 6.7%, 7.3% and 6.1% in men and 17%, 16.6%, 12% and 4.6% in women respectively. This index was 7.0% for smoking in men. High risk age contributed to 42% and 22% of risk in men and women respectively.
Conclusions
The incidence in this population of Iran was comparable to those in the US in the seventies. Well known modifiable risk factors explained about 40% and 50% of CHD burden in men and women respectively. Aging, as a reflection of unmeasured or unknown risk factors, bears the most burden of CHD, especially in men; indicating more age-related health care is required.
doi:10.1371/journal.pone.0105804
PMCID: PMC4146560  PMID: 25162590
8.  No Obesity Paradox—BMI Incapable of Adequately Capturing the Relation of Obesity with All-Cause Mortality: An Inception Diabetes Cohort Study 
Background. To reconcile “the obesity paradox,” we tested if (1) the contribution of anthropometric measures to mortality was nonlinear and (2) the confounding of hip circumference contributed to the obesity paradox recently observed among diabetic patients. Methods. We analyzed data of diabetic patients attending a community-based prospective, “Tehran lipid and glucose study.” In the mortality analysis, anthropometric measures—body mass index (BMI), waist, and hip circumference—were assessed using Cox models incorporating cubic spline functions. Results. During 12 990 person-years follow-up, BMI levels below 27 and those above 40 kg·m−2 were associated with increased mortality. When we added waist circumference to the BMI in the multivariate-adjusted model, the steepness of BMI-mortality association curve slope for values below 27 kg·m−2 increased, whereas the steepness of BMI-mortality association curve slope for values above this threshold decreased. Further adjusting the model for hip circumference, the steepness of the slopes of the association curve moved towards null on both extremes and no associations between BMI and all-cause mortality remained. Conclusion. BMI harbors intermixed positive and negative confounding effects on mortality of waist and hip circumference. Failing to control for the confounding effect of hip circumference may stymie unbiased hazard estimation and render conclusions paradoxical.
doi:10.1155/2014/282089
PMCID: PMC4142289  PMID: 25180034
9.  The association between inflammatory markers and obesity-related factors in Tehranian adults: Tehran lipid and glucose study 
Objective(s):
Obesity considered being a low-grade inflammatory disease. The objective of this study was to examine the association between inflammatory markers (IM) including C-reactive protein (hs-CRP), Interleukin-6 (IL-6), and homocystein (Hcy) and obesity-related factors (e.g. BMI, waist, hip) in adult participants of Tehran lipid and glucose study (TLGS).
Materials and Methods:
In this cross-sectional study, 352 individuals (132 men and 220 women), age ≥19 years, were randomly recruited from participants of TLGS population. The serum levels of hs-CRP, IL-6, Hcy were determined using the enzyme linked immunosorbent assay (ELISA) method. Variables were compared by sample t-test. Bivariate linear correlation was estimated using Pearson's correlation coefficient. Linear regression analysis was applied to investigate the association between IMs and anthropometric and biochemical variables.
Results:
The mean age of participants was 46.1±16.1 years. abdominal obesity was present in 199(56.5%) individuals. levels of hs-CRP and IL-6 increased in the abdominally obese group (1507±3.3 vs. 577.8±4.3 ng/ml P<0.001) (3.6±3.3 vs. 1.9±3.8 pg/ml P< 0.001), and in the same group, the best predictors for hs-CRP, IL-6 and Hcy were waist (WC), waist to height ratio (WHtR) and wrist respectively; hip and WHtR were the best predictors for Hcy and hs-CRP in the normal group. A linear augmentation in hs-CRP and IL-6 levels was observed in association with obesity categorizes.
Conclusion:
This study provides evidence that abdominally obese individuals had higher levels of IMs. Wrist, waist and WHtR were the best predictors for Hcy, hs-CRP and IL-6 respectively in this group.
PMCID: PMC4240791  PMID: 25422750
Hcy; hs-CRP; IL-6; Inflammatory markers; Obesity; TLGS
10.  Sex Specific Incidence Rates of Type 2 Diabetes and Its Risk Factors over 9 Years of Follow-Up: Tehran Lipid and Glucose Study 
PLoS ONE  2014;9(7):e102563.
Objective
To investigate the population-based incidence of type 2 diabetes and its potential risk factors in a sex-split cohort of Iranian population.
Materials and Methods
A total of 8400 non-diabetic participants, aged ≥20 years (3620 men and 4780 women) entered the study. Crude and age standardized incidence rates per 1000 person-years were calculated for whole population and each sex separately. Cox proportional hazard models were used to evaluate hazard ratios (HR) and 95% confidence intervals for all potential risk factors in both uni-variable and multivariable models.
Results
During a median follow-up of 9.5 years, 736 new cases of diabetes were identified, including 433 women and 303 men. The annual crude and age-standardized incidence rates (95% CI) of diabetes in the total population were 10.6 (9.92–11.4) and 9.94 (7.39–13.6) per 1000 person-years of follow-up and the corresponding sex specific rates were 10.2 (9.13–11.4) and 9.36 (5.84–14.92) in men and 11.0 (9.99–12.0) and 10.1 (7.24–13.9) in women, respectively. In the multivariable model, the risk for incident diabetes was significantly associated with fasting and 2 hour post challenge plasma glucose as well as family history of diabetes in both men and women. However, among women, only the contribution of wrist circumference to incident diabetes achieved statistical significance [HR: 1.16 (1.03–1.31)] with waist/height ratio being marginally significant [HR: 1.02 (0.99–1.04)]; while among men, only body mass index was a significant predictor [HR: 1.12 (1.02–1.22)]. Additionally, low education level conferred a higher risk for incident diabetes only among men [HR: 1.80 (1.23–2.36); P for interaction with sex = 0.003].
Conclusion
Overall, sex did not significantly modify the impact of risk factors associated with diabetes among Iranian adults; however, among modifiable risk factors, the independent role of lower education and general adiposity in men and central adiposity in women might require different preventive strategies.
doi:10.1371/journal.pone.0102563
PMCID: PMC4100911  PMID: 25029368
11.  Alterations in Food Group Intakes and Subsequent Weight Changes in Adults: Tehran Lipid and Glucose Study 
Background:
The extent of weight change is varied for specific foods. This highlights the effect of dietary quality and food choices on weight control.
Objectives:
The aim of this study was to examine the association between alterations in food group intake and weight change over a 3 years follow-up period.
Materials and Methods:
This longitudinal study was conducted on 851 adults in the framework of Tehran Lipid and Glucose Study. Intakes of various foods were measured at baseline and after 3 years using a validated semi-quantitative food frequency questionnaire. Dietary data was grouped into 13 food groups. Alterations in food group intakes were categorized in tertiles; middle tertile of intake changes was considered as the reference category and the first and last tertiles of changes as increased and decreased intakes, respectively. Weight change per year of follow-up was the outcome of interest. Weight gain was defined as ≥ 0.5 kg/y, weight loss as ≤ -0.5 kg/y and stable weight as > -0.5 to < 0.5 kg/y. Multinomial logistic regression was used with stable weight as the reference group.
Results:
In men, weight loss was significantly predicted only by decreased intake of added sugars (OR: 2.21, 95% CI: 1.06-4.63). In women, weight gain was significantly predicted by decreased intake of whole grains (OR: 1.92, 95% CI: 1.11-3.31) and weight loss was predicted by decreased intake of vegetables (OR: 0.44, 95% CI: 0.21-0.91).
Conclusions:
Alterations in consumption of whole grains, vegetables, and added sugars are associated with body weight change, suggesting that it could be helpful in weight control.
doi:10.5812/ijem.17236
PMCID: PMC4166206  PMID: 25237324
Body Weight Changes; Longitudinal Studies; Lipids; Glucose
12.  Dietary phytochemical index and subsequent changes of lipid profile: A 3-year follow-up in Tehran Lipid and Glucose Study in Iran 
ARYA Atherosclerosis  2014;10(4):203-210.
BACKGROUND
High intakes of phytochemical-rich foods have beneficial effects on lipid profiles and cardiovascular disease (CVD). In this study, we assessed the association between the dietary phytochemical index (PI) and changes in lipid profile after 3-year follow-up among Iranian adults.
METHODS
This longitudinal study was conducted in 1983 subjects, aged 19-70 years, selected among participants of the Tehran Lipid and Glucose Study in Iran. Dietary data were collected by using a validated semi-quantitative food frequency questionnaire with 168 food items at baseline. PI was calculated based on daily energy derived from [(phytochemical-rich foods kcal/total daily energy intake kcal) × 100]. Lipid profile was measured at baseline and after 3 years and changes in serum lipid profiles were assessed during 3-year follow-up.
RESULTS
The mean age of participants was 40.4 ± 13.0 years; participants in the highest PI quartile category were more likely to be older. After 3 years of follow-up, total cholesterol was significantly lower in the highest quartile compared with lower quartile of PI in men (181 ± 3 vs. 189 ± 3, P for trend < 0.05). There were significant inverse association between dietary PI and 3 years changes of total cholesterol [β = −5.6, 95% confidence interval (CI) = −9.3, −1.8], triglycerides (β = −13.7, 95% CI = −24.6, −2.8), and non-high-density lipoprotein cholesterol (HDL-C) (β = −6.2, 95% CI = −10.8, −1.5), in highest quartile of PI in men. Lipid profiles showed no significant changes over the study period in women.
CONCLUSION
Higher dietary PI is associated with 3 years improvement of total cholesterol, triglycerides, and non-HDL-C. Higher consumption of phytochemical-rich foods is recommended to prevent CVD.
PMCID: PMC4173317  PMID: 25258636
Phytochemical; Triglyceride; Cholesterol; Fruit and vegetables; Whole Grains
13.  Functional foods-based diet as a novel dietary approach for management of type 2 diabetes and its complications: A review 
World Journal of Diabetes  2014;5(3):267-281.
Type 2 diabetes is a complicated metabolic disorder with both short- and long-term undesirable complications. In recent years, there has been growing evidence that functional foods and their bioactive compounds, due to their biological properties, may be used as complementary treatment for type 2 diabetes mellitus. In this review, we have highlighted various functional foods as missing part of medical nutrition therapy in diabetic patients. Several in vitro, animal models and some human studies, have demonstrated that functional foods and nutraceuticals may improve postprandial hyperglycemia and adipose tissue metabolism modulate carbohydrate and lipid metabolism. Functional foods may also improve dyslipidemia and insulin resistance, and attenuate oxidative stress and inflammatory processes and subsequently could prevent the development of long-term diabetes complications including cardiovascular disease, neuropathy, nephropathy and retinopathy. In conclusion available data indicate that a functional foods-based diet may be a novel and comprehensive dietary approach for management of type 2 diabetes.
doi:10.4239/wjd.v5.i3.267
PMCID: PMC4058731  PMID: 24936248
Type 2 diabetes; Insulin resistance; Functional foods; Whole grain; Legumes; Nuts; Fruits; Herbs or spices; Vegetables; Prebiotics; Probiotics
14.  A comparative study of broccoli sprouts powder and standard triple therapy on cardiovascular risk factors following H.pylori eradication: a randomized clinical trial in patients with type 2 diabetes 
Background
In this clinical trial we compared the effects of broccoli sprouts powder, as an alternative and complementary treatment, to those of standard triple therapy, as a common medical treatment, on cardiovascular risk factors following the H.pylori eradication in patients with type 2 diabetes.
Methods
Eighty-six type 2 diabetic patients with positive H.pylori stool antigen test (HpSAg) were randomized to receive one of the three following regimens: STT) Standard triple therapy (omeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, twice a day for 14 days), BSP) 6 g/d broccoli sprouts powder for 28 days, and combination of these as STT + BSP. After 4 weeks of treatment, H.pylori eradication rates were assessed by HpSAg. Anthropometric measures, blood pressure, serum lipids and lipoproteins as well as serum high sensitive- C reactive protein were also assessed at baseline and at the second examination.
Results
Seventy-seven participants completed the study [STT (n = 28), BSP (n = 25), STT + BSP (n = 24)]. The H.pylori eradication rates were 89.3%, 56.0% and 91.7% in STT, BSP and STT + BSP groups, respectively. After the treatment, both systolic and diastolic blood pressure significantly decreased in STT + BSP group (P < 0.05). Serum triglycerides and TG/HDL-C ratio increased in STT patients group (<0.05). Serum hs-CRP levels significantly decreased in the patients who were treated with BSP per se (3.0 ± 2.5 at baseline vs. 2.3 ± 2.1 after the treatment, P < 0.05).
Conclusion
Compared to standard triple therapy, BSP regimen in addition to considerable effects on H.pylori eradication had also favorable properties on cardiovascular risk factors following the H.pylori eradication.
doi:10.1186/2251-6581-13-64
PMCID: PMC4060758  PMID: 24940565
Helicobacter pylori; Standard triple therapy; Broccoli sprouts powder; High-sensitive C reactive protein; Cardiovascular risk factor
16.  The Time of Prenatal Androgen Exposure Affects Development of Polycystic Ovary Syndrome-Like Phenotype in Adulthood in Female Rats 
Background:
Polycystic ovary syndrome (PCOS) is one of the most common reproductive disorders in women. Previous studies have shown that prenatal exposure of female fetuses to androgen can be considered an important factor in the development of PCOS.
Objectives:
In the present study we aimed to examine the effects of prenatal exposure of female rat fetuses to previously documented doses of testosterone on different embryonic days on the development of PCOS phenotype in adulthood.
Materials and Methods:
Pregnant rats were divided into four groups, experimental and control groups. Three mg of free testosterone was administered subcutaneously to experimental group 1 on gestational days 16-19, daily and 20 mg on day 20, to experimental group 2, and the controls received solvent at the same times. Female offspring of these mothers aged between 90-100 days were examined for development and function of the reproductive system. Independent-sample student t test was used to compare the results between the experimental groups and controls.
Results:
Anogenital distance (P < 0.001) and clitoris length were significantly increased in the offspring of both experimental groups (P < 0.001 and P < 0.05 respectively). Nipples were not formed in the offspring of experimental group 1, whereas in experimental group 2 the number of nipples was unchanged. Vaginal length was significantly decreased in the offspring of experimental group 1 (P < 0.001), whereas in experimental group 2, no significant difference was observed. In the offspring of experimental group 1, hormonal profiles did not differ, but in experimental group 2, levels of testosterone (P < 0.05) and LH (P < 0.01) were significantly increased, but estrogen (P < 0.05) and anti-Mullerian hormone levels (P < 0.001) were significantly decreased. A significant increase in the number of preantral and antral follicles was observed in the ovaries of offspring of experimental group 1 (P < 0.05); whereas there was no such a difference in experimental group 2.
Conclusions:
The time of prenatal exposure to androgens may have a significant role in the development of PCOS. Increased prenatal androgen levels are associated with hormonal changes and morphological disorders of the reproductive system. Therefore, avoiding exposure to androgen excess during critical periods of fetal development may prevent or reduce adulthood PCOS manifestations caused by prenatal excess androgen.
doi:10.5812/ijem.16502
PMCID: PMC4030220  PMID: 24910644
Androgens; Exposure Time; Fetus; Polycystic Ovary Syndrome; Rats
17.  Identification and Determination of Synthetic Pharmaceuticals as Adulterants in Eight Common Herbal Weight Loss Supplements 
Background:
Adulterated herbal weight loss products with containing undeclared synthetic drugs are common and responsible for many serious health damages.
Objectives:
The purpose of the study was to determine five synthetic adulterants in eight common herbal weight loss supplements, which are currently sold in Iran markets, to verify their presence in supplements, without mentioning on the labels.
Materials and Methods:
Eight common herbal weight loss samples were obtained from the Iran pharmaceutical market after advertising in the Persian language on satellite channels and internet. Five pharmacological classes of drugs used for weight loss, namely sibutramine, phenolphthalein, phenytoin, bumetanide and rimonabant, were investigated and quantified by GC-MS for the first three and LC-MS for the last two medications.
Results:
The most undeclared ingredients, which were illegally added include sibutramine, phenolphthalein, bumetanide, and phenytoin in the original super slim, herbaceous essence, super slim green lean, and fat loss, supplements, respectively. Rimonabant was not found. Caffeine, pseudoephedrine, theobromine and amfepramone were also found in the supplements using GC-MS assay.
Conclusions:
Adulterated synthetic substances were detected in the herbal weight loss products. Health care professionals should make people aware of the risks of taking herbal weight-loss supplements.
doi:10.5812/ircmj.15344
PMCID: PMC4005444  PMID: 24829782
United States Food and Drug Administration; Herbal Medicine; Weight Loss; Gas Chromatography-Mass Spectrometry
18.  Secular trends in serum lipid levels of a Middle Eastern adult population; 10 years follow up in Tehran lipid and glucose study 
Background
To examine trends in the population levels of serum lipids among a Middle-Eastern adult population with high prevalence of dyslipidemia.
Methods
A population-based cohort of adult Iranian participants, aged ≥20 years underwent four consecutive examinations between 1999–2001 and 2008–2011. Trends in age and multivariate-adjusted mean lipid levels were calculated using generalized estimating equations.
Results
At each of the 4 assessments, there were significant decreases in levels of total cholesterol (TC) (multivariate-adjusted means, 5.21 vs. 4.88 mmol/L in men; 5.42 vs. 5.07 mmol/L in women), triglycerides (TGs) (2.11 vs. 1.94 mmol/L in men; 1.88 vs. 1.74 mmol/L in women), and an increase in HDL-C level in both genders (0.95 vs. 1.058 mmol/L in men; 1.103 vs. 1.246 mmol/L in women) in multivariate analyses (all Ps <0.001); however, body mass index (BMI) significantly increased simultaneously (25.92 vs. 27.45 kg/m2 in men; 27.76 vs. 30.02 kg/m2 in women) (P < 0.001). There were significant (P < 0.001) increases in fasting plasma glucose (FPG) levels only among men (5.35 vs. 5.73 mmol/L). Results did not change after excluding participants that had cardiovascular disease or used lipid lowering drugs during follow-up. There were significant decreases in the prevalence of hypercholesterolemia, low HDL-C, hypertriglyceridemia (all Ps <0.001) during follow-up. Furthermore, the consumption of lipid lowering drugs significantly increased (P <0.001).
Conclusion
During a 10 years follow-up, favorable trends were observed in the population levels of TC, triglycerides, HDL-C, which could not be fully accounted for by the increase observed in the consumption of lipid lowering drugs. These favorable trends were counterbalanced by the progressive increase in general obesity and FPG level.
doi:10.1186/1476-511X-13-20
PMCID: PMC3912503  PMID: 24456699
Secular trends; Serum lipids measures; Middle Eastern adult population; Cohort; Dislipidemia
19.  Leemoo, a Dietary Assessment and Nutritional Planning Software, Using Fuzzy Logic 
Background:
Leemoo is a user-friendly software designed for nutritional planning and dietary assessment applications by cooperation of Research Institute for Endocrine Sciences of Shahid Beheshti University of Medical Sciences, which uses fuzzy logic for the first time. It provides a range of recommended servings for food groups, which are easier for people to follow.
Objectives:
The aim of this research was to describe the applications of this newly introduced software.
Methods and Materials:
Leemoo contains the following databases: food, nutrients, MyPyramid equivalents and physical activity. These databases facilitate diet analysis and planning. The food composition database includes 2920 Iranian food items, with the nutrient composition for up to 64 nutrients.
Results:
All databases are flexible for updating. The program can calculate the amounts of nutrients and food group intakes and compare these with Dietary Reference Intakes and MyPyramid recommendations. This software has the ability of nutritional planning and estimates normal intake ranges of seven food groups based on person need.
Conclusions:
This software was envisaged for use by health professionals, researchers and ordinary people and can be recommended for educational purpose and nutrition research in Iran. Future studies must be conducted to evaluate the effects of this software on users’ dietary habits and nutrition knowledge.
doi:10.5812/ijem.10169
PMCID: PMC3968974  PMID: 24719623
Nutrition Software; Leemoo; Fuzzy Logic; Food Groups
20.  Incidence of Metabolic Syndrome over 9 Years Follow-Up; the Importance of Sex Differences in the Role of Insulin Resistance and Other Risk Factors 
PLoS ONE  2013;8(9):e76304.
To determine, the predictors of incident metabolic syndrome (MetS) in a community-based cohort of West Asians, during a mean follow-up of 9.3 years, a sample of 2858 non-MetS Iranian adults aged ≥ 20 years were examined at baseline and followed at three year intervals during three consecutive phases. The MetS was defined using the joint interim statement. Cox proportional hazard regression was used to determine the independent variables associated with incident MetS. Overall, 1117 new cases MetS were identified resulting in an incidence rate of 550.9/10000 person years (95% CI: 519.5-584.2). The corresponding incidence rates among women and men were 433.5/10000 person years (95% CI: 398.8-471.2) and 749.2/10000 person years (95% CI: 689.9-813.5), respectively. Baseline-adjusted predictors of developing MetS included all of the MetS components, being overweight or obese in both gender, and family history of diabetes and age only in women. There were significant effect modifications of gender on age (P<0.001), high blood pressure (0.026), high waist circumference (P<0001) and obesity categories (all P ≤ 0.01) in multivariate analysis. After considering HOMA–IR in the model, among women, all of the MetS predictors as well as those with HOMA-IR ≥ 2.23 showed a significant risk for incident MetS [HR: 1.63 (1.16-2.28)]; however, among men all the MetS components (WC was marginally significant) as well as the fourth quartile of HOMA-IR [HR: 1.50 (1.03-2.17)] and being overweight showed a significant risk. Finally, in the pooled analysis, we showed that female gender had lower risk for incident MetS than male [HR: 0.58 (0.47-0.70)]. In the Iranian population, high incidence of MetS, especially among men, was shown. Our findings confirmed that sex- specific risk predictors should be considered in primary prevention for incident MetS.
doi:10.1371/journal.pone.0076304
PMCID: PMC3785433  PMID: 24086723
21.  Association between Physical Activity and Metabolic Risk Factors in Adolescents: Tehran Lipid and Glucose Study 
Background:
Physical activity (PA) is associated with the metabolic syndrome (MetS) and its components. This study aimed to examine the association between PA and MetS and its components among normal weight and overweight/obese adolescent in Tehran Lipid and Glucose Study (TLGS).
Methods:
This cross-sectional study includes 777 adolescents, aged 12-18 years, who were selected by multi-stage random cluster sampling from among TLGS participants. Subjects were classified as normal weight and overweight/obese based on the age- and sex-specific standardized percentile curves of BMI for Iranian population. Levels of PA were assessed using a standardized and modifiable activity questionnaire (MAQ), and categorized into tertiles. MetS was defined according to the Cook's criteria.
Results:
Prevalence of the MetS was higher in overweight/obese than normal group (35% vs. 3%; P: 0.02). Normal groups were more physically active (50% vs. 44%); however, difference was not significant. There was a significant association between the light PA and risk of lower level of HDL-C before and after adjustment, in normal weight group (OR: 1.61, CI 95%: 1.11, 2.35; OR: 1.65, CI 95%: 1.12, 2.44, respectively). The overweight/obese group with light and moderate PA had a higher risk of having abdominal obesity than those with vigorous PA, only after adjustment for determined covariates (OR: 1.11, CI 95%: 1.07, 1.21; OR: 1.06, CI 95%: 1.01, 1.08, respectively); the association between MetS and PA was not significant.
Conclusions:
The results of this study confirm the association between PA and some individual components of MetS such as waist and HDL-C.
PMCID: PMC3793481  PMID: 24130941
Adolescent; metabolic syndrome; obesity; physical activity; TLGS
22.  Prenatal Testosterone Exposure Worsen the Reproductive Performance of Male Rat at Adulthood 
PLoS ONE  2013;8(8):e71705.
The reproductive system is extremely susceptible to environmental insults, for example exogenous steroids during gestational development and differentiation. Experimental induction of androgen excess during prenatal life in female animal models reprograms their reproductive physiology, however the fetal programming of the male reproductive system by androgen excess has not been well studied. We aimed to determine the effect of prenatal exposure of two different doses of testosterone on different gestational days, on the male reproductive system using a rat model. Sixteen pregnant rats were randomly divided into two experimental groups and two control groups. Experimental group І were subcutaneously injected with 3 mg free testosterone on gestational days 16-19 and its controls received solvent for that time; experimental group П were subcutaneously injected with 20 mg free testosterone on day 20 of gestational period and its controls received solvent at the same time. The reproductive system morphology and function of 32 male offspring of these study groups were compared at days 6-30-60 of age and after puberty. The anogenital distance of the male offspring of both experimental groups had no significant differences on the different days of measurement, compared with controls. In the offspring of experimental group І, the testes weight, number of Sertoli, Spermatocyte and Spermatid cells, sperm count and motility and the serum concentration of testosterone after puberty were significantly decreased; except for reduction of sperm motility (p< 0.01), the other effects were not observed in the offspring of experimental group ІІ. In summary, our data show that prenatal exposure of male rat fetuses to excess testosterone disrupted reproductive function, an effect highly dependent on the time, duration and level of exposure. It seems that the reproductive system in individuals exposed to high levels of androgens during fetal life should be evaluated at puberty and likely to be treated.
doi:10.1371/journal.pone.0071705
PMCID: PMC3744450  PMID: 23967236
23.  Dietary polyphenols as potential nutraceuticals in management of diabetes: a review 
In recent years, there is growing evidence that plant-foods polyphenols, due to their biological properties, may be unique nutraceuticals and supplementary treatments for various aspects of type 2 diabetes mellitus. In this article we have reviewed the potential efficacies of polyphenols, including phenolic acids, flavonoids, stilbenes, lignans and polymeric lignans, on metabolic disorders and complications induced by diabetes. Based on several in vitro, animal models and some human studies, dietary plant polyphenols and polyphenol-rich products modulate carbohydrate and lipid metabolism, attenuate hyperglycemia, dyslipidemia and insulin resistance, improve adipose tissue metabolism, and alleviate oxidative stress and stress-sensitive signaling pathways and inflammatory processes. Polyphenolic compounds can also prevent the development of long-term diabetes complications including cardiovascular disease, neuropathy, nephropathy and retinopathy. Further investigations as human clinical studies are needed to obtain the optimum dose and duration of supplementation with polyphenolic compounds in diabetic patients.
doi:10.1186/2251-6581-12-43
PMCID: PMC3751738  PMID: 23938049
Polyphenols; Phenolic acids; Flavonoids; Stilbenes; Lignans; Type 2 diabetes; Diabetes complications
24.  Trimester-Specific Reference Ranges for Thyroid Hormones in Iranian Pregnant Women 
Journal of Thyroid Research  2013;2013:651517.
Background. Due to many physiological changes during pregnancy, interpretation of thyroid function tests needs trimester-specific reference intervals for a specific population. There is no normative data documented for thyroid hormones on healthy pregnant women in Iran. The present survey was conducted to determine trimester-specific reference ranges for serum TSH, thyroxine (TT4), and triiodothyronine (TT3). Methods. The serum of 215 cases was analyzed for measurement of thyroid function tests by immunoassay method of which 152 iodine-sufficient pregnant women without thyroid autoantibodies and history of thyroid disorder or goiter were selected for final analysis. Reference intervals were defined as 5th and 95th percentiles. Results. Reference intervals in the first, second, and third trimesters were as follows: TSH (0.2–3.9, 0.5–4.1, and 0.6–4.1 mIU/l), TT4 (8.2–18.5, 10.1–20.6, and 9–19.4 μg/dl), and TT3 (137.8–278.3, 154.8–327.6, and 137–323.6 ng/dl), respectively. No correlation was found between TSH and TT4 or TT3. Significant correlation was found between TT4 and TT3 in all trimesters (r = 0.35, P < 0.001). Conclusion. The reference intervals of thyroid function tests in pregnant women differ among trimesters. Applying trimester-specific reference ranges of thyroid hormones is warranted in order to avoid misclassification of thyroid dysfunction during pregnancy.
doi:10.1155/2013/651517
PMCID: PMC3690831  PMID: 23841018
25.  The Effect of Community-Based Education for Lifestyle Intervention on The Prevalence of Metabolic Syndrome and Its Components: Tehran Lipid and Glucose Study 
Background:
It has been shown that life style modification may decrease the prevalence of metabolic syndrome, but this intervention has not been reported in community setting.
Objectives
Effect of lifestyle modification on prevalence of metabolic syndrome and its components were assessed in an urban population.
Materials and Methods:
In 6870 participants of Tehran Lipid and Glucose Study aged 20-74 years, the prevalence of metabolic syndrome and its components were measured before and after a 3.6 years interval. Lifestyle intervention was employed at a community level including 2961 individuals and also 3909 subjects which were recruited as controls. Logistic regression analysis was adjusted for age, sex and medications.
Results
After 3.6 years, the rise in the prevalence of metabolic syndrome was less prominent in intervention than control group (P < 0.002 for increase of metabolic syndrome prevalence between groups), with an OR of 0.84 (confidence interval 0.75-0.95). After intervention the prevalence of abdominal obesity, elevated fasting glucose levels, elevated triglyceride and low HDL cholesterol were more prominent in control group, as compared to intervention group.
Conclusions:
Community based lifestyle modifications in Tehranian adults delayed rise in the prevalence of metabolic syndrome and some of its components.
doi:10.5812/ijem.5443
PMCID: PMC3860109  PMID: 24348586
Metabolic Syndrome; Lifestyle; Community-Based; Prevalence

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