Comprehensive evaluation of body composition in a wide age range of Iranian adults using bioelectrical impedance analysis: Tehran Lipid and Glucose Study.

OBJECTIVE: To evaluate sex- and age-stratified body composition (BC) parameters in subjects with wide age range of 20-79 years. DESIGN: Cross-sectional. SETTING: Participants of Tehran Lipid and Glucose Study (TLGS). PARTICIPANTS: Two thousand nine hundred seventy participants met our inclusion criteria. They were divided into five age groups, and BC parameters were analysed based on sex and age using a bioelectrical impedance analyser (BIA). RESULT: The mean age of the participants was 42·1 ± 12·5 years, and 54 % of them were males. The mean BMI was 26·7 ± 3·7 kg/m2. Obesity indices were significantly higher in females (P < 0·001); however, skeletal muscle mass (SMM) and fat-free mass (FFM) were significantly higher in males (P < 0·001). Both SMM and FFM decreased significantly after the age of 50 years. Obesity indices significantly increased from the age group of 20-29 to 30-39 years in males and the age groups of 30-39 to 40-49 years and 40-49 to 50-59 years in females. The fat mass ratio (fat mass/SMM) showed two peaks in both sexes (after the ages of 30 and 50 years in males and 40 and 50 years in females). A strong correlation was found between BMI and percentage of body fat (r = 0·823 in females v. r = 0·768 in males). CONCLUSION: This is the first community-based study in the MENA region identifying sex- and age-stratified BC values using BIA. Our findings can be used as a reference for comparison in appropriate settings.

Body Composition Assessment by Bioelectrical Impedance Analysis in Prediction of Cardio-Metabolic Risk Factors: Tehran Lipid and Glucose Study (TLGS).

Background: We aimed at evaluating the best body mass index (BMI) and percent body fat (PBF) cutoffs related to cardio-metabolic risk factors and comparing the discriminative power of PBF and BMI for predicting these risk factors. Methods: In this cross-sectional study in phase V (2012-2015), 1271 participants (age ≥ 20 yr; 54.3% women) were enrolled. Bioelectrical impedance analysis (BIA) was used to estimate PBF. Joint Interim Statement criteria were used for defining metabolic syndrome (MetS). We compared PBF with BMI through logistic regression and area under the curve of the receiver operating characteristic (ROC) curve. Percent body fat cutoff points were > 25 in men and >35 in women. Results: Percent body fat and BMI cutoff points for predicting MetS were 25.6% and 27.2 kg/m2 in men and 36.2% and 27.5 kg/m2 in women, respectively. There were no significant differences between BMI and PBF area under the ROC curves for predicting MetS and its components, except for abdominal obesity in men and low high-density lipoprotein (HDL) in women in favor of BMI. Logistic regression analysis indicated that BMI in women was better for predicting MetS and its components, except for abdominal obesity. Moreover, BMI was equal or superior to PBF in men, except for low HDL and high triglyceride levels. Conclusion: Comparison of PBF with BMI showed that the use of PBF is not significantly better than BMI in predicting cardio-metabolic risks in the general population.

Antineoplastic Activity of an Old Natural Antidiabetic Biguanide on the Human Thyroid Carcinoma Cell Line.

BACKGROUND: In the last decades, metformin (Met), an herbal anti-diabetic medicine, has been proposed as an anti-cancer agent. OBJECTIVE: Thyroid cancers are the most common malignancy of the endocrine system. Therefore, the current study was performed to assess the effects of Met on cell proliferation and activation of the Phosphoinositide 3- Kinase (PI3K)/Protein kinase B (AKT)/Forkhead Box O1 (FOXO1) signaling pathway in the Medullary Thyroid Carcinoma (MTC) cells. The effects of Met on the expression of REarranged during Transfection (RET) proto-oncogene were also investigated. METHODS: MTC cell line (TT) was treated with 0, 2.5, 5, 10, 20, 30, 40, 50, and 60 mM concentrations of Met for 24, 48, and 72h. The viability and apoptosis of the treated cells were measured by the 3-(4,5-Dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Annexin V- Propidium Iodide (PI) assays. The expression level of PI3K, AKT, FOXO1, and RET genes was investigated by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), and phosphorylation of their proteins was determined by the Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Results showed that Met significantly decreased the viability of the MTC cells. Met also reduced the expression level of PI3K, AKT, and FOXO1 genes (P<0.05), whereas it elevated the expression level of RET proto-oncogene (P<0.05). CONCLUSION: It seems that the Met has a cytostatic effect on the TT cells. Our results showed that anti-tumoral effects of Met may be cell type-specific, and according to the induction of RET (as a proto-oncogene) and inhibition of FOXO1 (as a tumor suppressor gene), Met could not be an appropriate agent in the treatment of MTC. The antineoplastic activity of Met has been confirmed against several malignancies in "in vitro" and "in vivo" studies. However, its molecular mechanisms in the treatment of different carcinomas particularly in thyroid cancers are not clearly understood and more studies are required to confirm its exact effect on the MTC.

Effects of bariatric surgery in different obesity phenotypes: Tehran Obesity Treatment Study (TOTS).

BACKGROUND: Not all morbid obese patients suffer from metabolic co-morbidities; thus, a sub-group of metabolically healthy morbid obese (MHMO) individuals are identified. However, the role of bariatric surgery is not well understood in this subgroup. METHODS: A total of 2244 morbid obese individuals aged 18-65 years undergoing bariatric surgery were selected. Patients were considered MHMO according to the joint interim statement (JIS) definition, as having two or less abnormalities in these five parameters: waist circumference (WC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), systolic or diastolic blood pressure (SBP or DBP), and fasting plasma glucose (FPG). Otherwise, they were considered metabolically unhealthy morbid obese (MUMO). Follow-up data were collected at 6, 12, and 24 months post-surgery. RESULTS: Prior to surgery, 36.2% of participants were MHMO and had significantly lower BMI, WC, TG, FPG, SBP, and DBP and higher HDL-C compared to MUMO. Both MHMO and MUMO participants showed a significant decrease in BMI, WC, TG, SBP, DBP, and FPG and increase in HDL-C and the percentage of excess weight loss (%EWL). Two-year post-operative changes (from baseline) of BMI, WC, and %EWL were greater in MHMO subjects and changes of TG, HDL-C, DBP, SBP, and FPG were greater in MUMO subjects. Further multivariate regression analysis for delta (∆) change in these characteristics revealed that only the delta (∆) changes of WC and %EWL were statistically different between the two phenotypes and were greater in MHMO subjects, 2 years after the surgery (- 3.077 cm decrease in WC and + 3.612% higher %EWL compared to MUMO subjects). CONCLUSION: Bariatric surgery is an effective method for reduction of metabolic abnormalities and weight loss in both MUMO and MHMO phenotypes. Benefits of this intervention are comparable between patients with these two obesity phenotypes.

Effects of metformin on the PI3K/AKT/FOXO1 pathway in anaplastic thyroid Cancer cell lines.

BACKGROUND: The PI3K/AKT/FOXO signaling pathway plays an important role in the survival, proliferation and apoptosis of tumor cells. The aim of the present study was to explore whether metformin could affect insulin-promoting cell growth by regulation of this pathway. MATERIAL AND METHODS: Anaplastic thyroid cancer cells were treated with 0-60 mM metformin for 24, 48 and 72 h. Cell viability, morphology, apoptosis and migration were investigated by MTT assay, microscopy observation, AnexinV-PI and the wound healing assay, respectively. Expression levels of PI3K, AKT and FOXO1 were detected by RT-qPCR, and proteins phosphorylated levels were determined by ELISA. RESULTS: Metformin decreased cell viability and migration in a significant time-and dose-dependent manner, and induced apoptosis and morphological changes in the cells. RT-qPCR results showed that expression levels of PI3K, AKT and FOXO1 was inhibited by metformin (P < 0.05). However, there was no significant change in the expression level of AKT following metformin treatment for C643 cell line (P > 0.05). ELISA results showed that metformin treatment had no significant effects on the phosphorylated levels of PI3K, AKT and FOXO1 (P > 0.05). CONCLUSUION: The downregulation of FOXO1 was intensified by metformin, but no increase in cell viability was observed following FOXO1 downregulation by metformin. However, the exact molecular mechanism of metformin on inhibition of the PI3K/AKT pathway and subsequent decrease in cell viability remains unclear and further studies are required for its clarification.

Mortality prediction of a body shape index versus traditional anthropometric measures in an Iranian population: Tehran Lipid and Glucose Study.

OBJECTIVES: A body shape index (ABSI) based on waist circumference (WC) adjusted for height and weight has been shown to be a risk factor for premature mortality. The aim of this study was to demonstrate that ABSI predicts mortality hazard better than other anthropometric measures in an Iranian population. METHODS: The study population included 9242 Iranian participants in Tehran, aged ≥30 y, followed for a median 10 y. The risk for mortality was estimated by incorporating ABSI, body mass index (BMI), WC, waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR), one at a time, into multivariate models as well as in terms of the effect size, calibration, discrimination, and added predictive ability. RESULTS: We documented 487 deaths with the annual incidence rate of mortality per 1000 persons being 3.9 for women and 8.2 for men. ABSI was associated with all-cause mortality in a curvilinear fashion. ABSI was more strongly associated with all-cause mortality than were BMI, WC, and WHtR. Among women, however, WHpR was observed to be a stronger predictor of all-cause mortality than ABSI. Among both men and women, ABSI improved the risk classification based on other anthropometric measures, the only exception being WHpR. None of the anthropometric measures studied could add any value to the predictive ability of the Framingham's general cardiovascular disease algorithm. CONCLUSION: ABSI was the strongest predictor of all-cause mortality among the anthropometric measurements, except WHpR in women. When ABSI was added to the Framingham general cardiovascular disease algorithm, it failed to improve the predictive ability.

Relationship between polymorphism of insulin receptor gene, and adiponectin gene with PCOS.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex disease having both genetic and environmental components and candidate genes on obesity and insulin metabolism have been hypothesized to be involved in its etiology. OBJECTIVE: We examined the possible association of adiponectin and insulin receptor gene polymorphisms with PCOS. MATERIALS AND METHODS: A total of 186 women with PCOS using NIH criteria and 156 healthy women were recruited. Their samples were genotyped for the polymorphism in exon 17 and 8 of the insulin receptor gene or exon and intron 2 of the adiponectin gene. RESULTS: The distributions of genotypes and alleles of both polymorphisms were not different in women with PCOS and controls. There was no significant differences on the anthropometric and hormonal profiles of various adiponectin and insulin receptor genes polymorphisms among both groups. CONCLUSION: Adiponectin and insulin receptor gene polymorphisms are not associated with PCOS in a sample of Iranian population.

Systolic and diastolic blood pressure, mean arterial pressure and pulse pressure for prediction of cardiovascular events and mortality in a Middle Eastern population.

We compared systolic (SBP) and diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP) as independent predictors of cardiovascular disease (CVD), total and CVD mortality among an Iranian population. The study conducted among 5991 subjects aged ≥ 30 years without baseline CVD and antihypertensive medication. The mean of two measurements of SBP and DBP, in sitting position, was considered the subject's blood pressure. During a median follow-up of 8.7 years, 346 CVD and 157 deaths, 63 attributed to CVD, occurred. Hazard ratios (HRs) of each outcome were calculated for a one standard deviation (SD) increase in each blood pressure (BP) measures. In multivariate models, all BP measures were associated with increased risk of CVD regardless of age. In those aged < 60 years, SBP, DBP, PP and MAP were associated with total mortality (p < 0.05), but in subjects aged ≥ 60 years, only SBP and PP increased risk of total mortality significantly. In multivariate analyses, a 1SD increase in SBP, PP and MAP were associated with 35%, 31% and 28% increased risk of CVD mortality (p < 0.05). In terms of fitness and discrimination of models, DBP, PP and MAP were not superior to SBP. In conclusion, our findings provided further evidence from a Middle Eastern population, in support of SBP predictability for CVD events and CVD and all-cause mortality compared with other BP measures.

Lipid ratios and appropriate cut off values for prediction of diabetes: a cohort of Iranian men and women.

BACKGROUND: Dyslipidemia is a risk factor for incident type 2 diabetes; however, no study has specifically assessed the lipid ratios (i.e. total cholesterol (TC)/high density lipoprotein cholesterol (HDL-C) and triglyceride (TG)/HDL-C) as predictors of diabetes. We aimed to compare the independent association between the different lipid measures with incident diabetes over a median follow up of 6.4 years in Iranian men and women. METHOD: The study population consisted of 5201 non diabetic (men = 2173, women = 3028) subjects, aged > or =20 years. The risk factor adjusted odds ratios (ORs) for diabetes were calculated for every 1 standard deviation (SD) change in TC, log-transformed TG, HDL-C, non-HDL-C, TC/HDL-C and log-transformed TG/HDL-C using multivariate logistic regression analysis. Receiver operator characteristic (ROC) curve analysis was used to define the points of the maximum sum of sensitivity and specificity (MAXss) of each lipid measure as a predictor of diabetes. RESULT: We found 366 (146 men and 220 women) new diabetes cases during follow-up. The risk-factor-adjusted ORs for a 1 SD increase in TG, TC/HDL-C and TG/HDL-C were 1.23, 1.27 and 1.25 in men; the corresponding risks in females were 1.36, 1.14, 1.39 respectively (all p < 0.05, except TC/HDL-C in females which was marginally significant, p = 0.07). A 1 SD increase of HDL-C only in women decreased the risk of diabetes by 25% [0.75(0.64-0.89)]. In both genders, there was no difference in the discriminatory power of different lipid measures to predict incident diabetes in the risk factor adjusted models (ROC approximately 82%). TG cutoff values of 1.98 and 1.66 mmol/l; TG/HDL-C cutoff values of 4.7 and 3.7, in men and women, respectively, TC/HDL-C cutoff value of 5.3 in both genders and HDL-C cutoff value of 1.18 mmol/l in women yielded the MAXss for defining the incidence of diabetes. CONCLUSION: TC/HDL-C and TG/HDL-C showed similar performance for diabetes prediction in men population however; among women TG/HDL-C highlighted higher risk than did TC/HDL-C, although there was no difference in discriminatory power. Importantly, HDL-C had a protective effect for incident diabetes only among women.