Publications by authors named "Azadeh Aminianfar"

13 Publications

  • Page 1 of 1

Relationship between dietary diversity score and general health in female students.

Minerva Pediatr (Torino) 2021 Feb;73(1):50-58

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Background: Adolescence is a critical period with respect to mental and psychological issues. The role of nutrients is well known in health condition in adolescents, but little emphasis is placed on total diet quality. Dietary diversity score (DDS) is often used to assess diet quality. The objective of this study was to investigate the relationship between DDS and general health in girl students.

Methods: The present research is a cross-sectional study which used descriptive-analytical approach. A total of 384 high-school female students selected using proportional stratified sampling. Physical activity level, diet and general health information collected using International Physical Activity Questionnaire (IPAQ), Dietary Diversity Questionnaire (FAO-2013) and 28-item self-reported general health questionnaire (GHQ-28), respectively. In addition, weight, height and waist circumference (WC) measured. Data analyzed using Chi-Square test, one-way ANOVA and Multinomial Logistic Regression.

Results: Mean DDS was 4.43±1.09. After adjustment for confounders of age, body mass index, physical activity, socioeconomic status and nutritional supplement intake, students with higher DDS were less prone to general health disorders (P≤0.05).

Conclusions: These finding implicate higher DDS in adolescents may associate with better general health.
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http://dx.doi.org/10.23736/S2724-5276.16.04419-4DOI Listing
February 2021

The Association between Dietary Inflammatory Potential and Gastric Cancer: A Case Control Study.

Nutr Cancer 2021 Feb 9:1-10. Epub 2021 Feb 9.

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Objective: No report is available about diet-disease associations in the understudied region of Afghanistan. Although the inflammatory potential of diet has been linked with several cancers, information about gastric cancer is scarce. The present study aimed to investigate the relationship between the inflammatory potential of the diet and odds of gastric cancer in Afghanistan.

Methods: In this hospital-based case-control study, we enrolled 90 newly-diagnosed cases of gastric cancer and 180 age (±5) and sex-matched controls. All cases were pathologically confirmed gastric cancer patients, with no history of any type of other pathologically confirmed cancers. Controls were healthy individuals and relatives of patients in the hospital. Dietary assessment was done by a pre-tested food frequency questionnaire. DII was calculated based on energy-adjusted amounts of several foods and nutrients with inflammatory or anti-inflammatory potential, as introduced by earlier studies.

Results: Mean age of study participants was 54 years, of them 73% were males. After adjustment for age and sex, individuals in the highest tertile of the inflammatory potential of the diet were 2.47 times (95% CI: 1.31-4.66) more likely to have gastric cancer compared with those in the lowest tertile. Further adjustment for other potential confounders did not substantially affect the association; such that participants with the greatest inflammatory potential of the diet had approximately 3.59 times (95% CI: 1.16-11.02) increased odds of gastric cancer than those with the lowest adherence. Additional adjustment for BMI strengthened the association (OR: 3.75; 95% CI: 1.14-12.30).

Conclusion: We found a significant positive association between inflammatory potential of the diet and risk of gastric cancer. Further studies with prospective nature are required to confirm this association.
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http://dx.doi.org/10.1080/01635581.2021.1883682DOI Listing
February 2021

The effect of ketogenic diet on body composition and anthropometric measures: A systematic review and meta-analysis of randomized controlled trials.

Crit Rev Food Sci Nutr 2021 Jan 14:1-14. Epub 2021 Jan 14.

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran.

This study aimed to summarize earlier randomized controlled trials on the effects of ketogenic diet (KD) on body composition and anthropometric measures. Four databases were searched from inception to May 2020 using relevant keywords. All clinical trials investigating the effects of KD on body weight (BW), body mass index (BMI), waist circumference (WC), fat mass (FM), fat-free mass (FFM), lean body mass (LBM), visceral adipose tissue (VAT) and percentage body fat (PBF) in adults were included. Overall, 18 trials were included in the review. Pooled effect sizes revealed a significant effect of KD on BW (weighted mean differences [WMD]: -2.87 kg, 95% confidence interval [CI]: -3.84 to -1.89), BMI (WMD: -1.44 kg/ 95% CI: -2.07, -0.81), FM (WMD: -1.40 kg, 95% CI: -2.50, -0.30), FFM (WMD: -0.81 kg, 95% CI: -1.32, -0.30), LBM (WMD: -0.63 kg, 95% CI: -1.21, -0.06), WC (WMD: -3.23 cm, 95% CI: -4.38, -2.09), VAT (WMD: -28.91 g, 95% CI: -50.57, -7.24) and PBF (WMD: -2.81 kg, 95% CI: -3.82, -1.80), respectively. Taken together, the data suggest that KD has beneficial effects on BW, BMI, FM, FFM, LBM, WC, VAT, and PBF. However, the effectiveness of the long term effect of this dietary pattern is unclear.
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http://dx.doi.org/10.1080/10408398.2020.1867957DOI Listing
January 2021

Dietary intake of total, animal and plant proteins and the risk of coronary heart disease and hypertension: a systematic review and dose-response meta-analysis of prospective cohort studies.

Crit Rev Food Sci Nutr 2020 Nov 2:1-14. Epub 2020 Nov 2.

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Background & Objectives: Previous findings assessing the association between long-term protein intake and cardiovascular diseases (CVDs) are inconsistent. This study aimed to summarize previous investigations on the association between total, animal and plant proteins intake and the risk of coronary heart disease (CHD) and hypertension (HTN) in adults.

Methods: Related papers were found by searching through PubMed/Medline, Scopus, and Google Scholar up to April 2020. Prospective cohort studies examined the association between consumption of the dietary protein from different sources and the risk of CHD and HTN in general population, were included. The random-effects model was used to pool the reported relative risks (RR). Dose-response associations were modeled by restricted cubic splines.

Results: Thirteen prospective studies, in total, including 547,303 participants- 11,590 cases with total CHD and 5,620 with HTN- were included. Dietary intake of total protein was not significantly associated with the risk of total CHD (RR: 0.97; 95%CI: 0.90-1.05) and HTN (RR: 1.01; 95% CI: 0.90-1.14). Moreover, consumption of both dietary plant and animal protein was not related to the risk of total CHD and HTN. Dose-response analysis indicated that the risk of CHD and HTN did not change significantly with increasing dietary total protein intake from 10% to 25% of total calorie intake.

Conclusions: Dietary protein intake from different sources had no significant association with risk of CHD and HTN. Further high-quality research is needed to examine the potential mechanistic links between dietary protein intake and health outcomes.
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http://dx.doi.org/10.1080/10408398.2020.1841730DOI Listing
November 2020

The association between dietary glycemic index and load and risk of gestational diabetes mellitus: A prospective study.

Diabetes Res Clin Pract 2020 Dec 25;170:108469. Epub 2020 Sep 25.

Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular -Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran; Department of Community Nutrition, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

Aims: This study aimed to investigate the association between dietary GI and GL and risk of GDM in a group of pregnant women in Iran.

Methods: A number of 812 pregnant women were recruited in their first trimester in a prospective study. A validated 117-item semi-quantitative food frequency questionnaire was used to assess usual dietary intakes of participants at study baseline. Dietary GI and GL were calculated based on earlier publications. GDM was diagnosed based on the results of a fasting plasma glucose concentration and a 50-g, 1-h oral glucose tolerance test at 24-28 weeks of gestation. Cox proportional hazards model was used to compute relative risks (RRs) and 95% confidence intervals (CI) for GDM.

Results: Mean ± SD of age and BMI of study participants was 29.4 ± 4.84 y and 25.14 ± 4.08 kg/m, respectively at study baseline. Mean ± SD of dietary GI was 58 ± 7 and that of dietary GL was 176 ± 42. Overall, 28.4% (n = 231) of study population developed GDM at weeks 24-28 of pregnancy. After adjustment for potential confounding variables, we found that women in the highest tertile of dietary GL were 43% more likely to develop GDM than those in the lowest tertile (95% CI: 1.01, 2.00; P-trend = 0.03). However, no significant association was seen between dietary GI (RR for the highest tertile compared to the lowest: 0.85; 95% CI: 0.61, 1.20; P-trend = 0.37), and risk of GDM.

Conclusions: We found that women with the highest dietary GL were at a greater risk of developing GDM during pregnancy. No significant association was seen between dietary GI and risk of GDM.
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http://dx.doi.org/10.1016/j.diabres.2020.108469DOI Listing
December 2020

Higher Dietary Inflammatory Index Scores are Associated with Increased Odds of Benign Breast Diseases in a Case-Control Study.

J Inflamm Res 2020 5;13:61-69. Epub 2020 Feb 5.

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: Dietary inflammatory index (DII) is a new tool for assessing the inflammatory potential of diet. Since there is no study that has investigated the association of DII and benign breast diseases (BBD), the aim of our study was to compare DII scores in patients with and without BBD.

Methods: One hundred and eleven (111) subjects with BBD and 104 healthy women attending the Iranian Center for Breast Cancer affiliated with the Academic Center for Education, Culture and Research were enrolled in a case-control study. Dietary data collected using a 168‑item validated food frequency questionnaire (FFQ). Energy-adjusted DII was calculated based on FFQ. Socio demographic data were collected by interview. In addition, physical activity was measured by the International Physical Activity Questionnaire (IPAQ). Weight, height and waist circumference were also measured.

Results: After adjustment for multiple confounding variables, participants at the highest tertile of DII had increased OR for BBD (OR=1.7, 95% CI=0.75-3.95) (P-trend =0.04).

Conclusion: The increased chance of BBD was suggested with a higher consumption of diets with inflammatory potential. However, this result should be interpreted with caution as OR was not statistically significant. Interventional studies are warranted to elucidate the role of inflammatory diets in the development of BBD.
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http://dx.doi.org/10.2147/JIR.S232157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008174PMC
February 2020

Association between adherence to MIND diet and general and abdominal obesity: a cross-sectional study.

Nutr J 2020 02 17;19(1):15. Epub 2020 Feb 17.

Integrative Functional Gastroenterology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Recently, a new eating pattern called as "Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND)" has been coined. Emerging studies are examining this dietary pattern with chronic conditions. We aimed to investigate the association between the MIND diet score and general and central obesity among adults.

Methods: This cross-sectional study was conducted in a framework of the Study on the Epidemiology of Psychological Alimentary Health and Nutrition (SEPAHAN). Dietary information was collected using a validated self-administered 106-item Willett-format dish-based semi-quantitative food frequency questionnaire (DS-FFQ) in 6724 adults. Adherence to the MIND diet was examined based on components suggested in this eating pattern. Anthropometrics data were collected using a validated self-reported questionnaire. General obesity was defined as body mass index ≥30 kg/m, and abdominal obesity as waist circumference > 102 cm for men and > 88 cm for women.

Results: Mean age, BMI and WC in the study population was 36.8 ± 8.08 y, 24.9 ± 3.8 kg/m and 83.7 ± 16.02 cm, respectively. Overall, 9.5% of subjects were generally obese and 24.4 were abdominally obese. Examining the whole study population, we found no significant association between the MIND diet score and odds of general obesity, either before (ORs for comparing T3 vs. T1: 1.03; 95% CI: 0.83, 1.27; P-trend = 0.74) or after controlling for potential confounders (ORs for T3 vs. T1: 0.91; 95% CI: 0.67, 1.25; P-trend = 0.58). This was also the case for men and women when analyzed separately. We also failed to find any significant association between the MIND diet score and odds of abdominal obesity after controlling for potential confounders in the whole study population (ORs for T3 vs. T1: 1.00, 95% CI: 0.79, 1.27; P-trend = 0.87). However, women with the greatest adherence to the MIND diet were 19% less likely to be abdominally obese than those with the lowest adherence in crude model (OR = 0.81; 95% CIs: 0.67, 0.98; P-trend = 0.03). This association disappeared after controlling for potential confounders (OR = 0.87; 95% CIs: 0.66, 1.14; P-trend = 0.55).

Conclusion: No significant association was observed between adherence to the MIND diet and odds of general and central obesity.
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http://dx.doi.org/10.1186/s12937-020-00531-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026971PMC
February 2020

Dietary Phytochemical Index and Benign Breast Diseases: A Case-Control Study.

Nutr Cancer 2020 2;72(6):1067-1073. Epub 2019 Sep 2.

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

: Dietary phytochemical index (DPI) is an inexpensive method for estimating the amounts of phytochemicals in foods. No study has investigated the association of DPI and benign breast diseases (BBD). Our study aimed to compare DPI in patients with BBD and the control group. This is a case-control study of 115 subjects with BBD and 116 healthy women attending the Iranian Center for Breast Cancer affiliated with Academic Center for Education, Culture and Research. Energy-adjusted DPI was calculated based on data collected from 168-item validated food frequency questionnaire. Sociodemographic data, physical activity, and anthropometric measures such as body weight, height, and waist circumference were determined. After adjustment for age, estrogen therapy, family history of breast disease, intake of dietary supplement, menopause status, waist circumference and physical activity, the odds ratio (OR) of BBD across the energy-adjusted DPI quartiles decreased significantly (OR = 0.3, 95%CI = 0.12-0.93) (‑trend = 0.02). We found that higher DPI score is related to lower BBD OR. This simple method may be used for the improvement of dietary intake to prevent BBD.
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http://dx.doi.org/10.1080/01635581.2019.1658795DOI Listing
September 2019

The association between the dietary inflammatory index and glioma: A case-control study.

Clin Nutr 2020 02 14;39(2):433-439. Epub 2019 Feb 14.

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran; Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular - Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Community Nutrition, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

Background & Aims: Dietary inflammatory potential has been associated with several cancers. However, the relationship between the dietary inflammatory index (DII®) and glioma is not clear. The aim of this study was to examine DII in relation to glioma.

Methods: In a hospital-based case-control study, we selected 128 newly-diagnosed cases of glioma and 256 controls. Cases were medically confirmed glioma patients, with no history of other cancers. A validated food frequency questionnaire was used to assess diet. DII scores were calculated based on the quantity of dietary components with inflammatory or anti-inflammatory potential. We used conditional logistic regression models to examine the association between the DII and glioma.

Result: Study participants were on average 43 years old and predominantly male (58%). After controlling for age, sex and energy intake, individuals in the highest quartile of DII had 87% (95% CI: 1.00-3.47) increased risk of glioma compared to those in the lowest quartile. Additional adjustment for environmental confounders strengthened the relationship; participants with the greatest DII scores had approximately 2.1 times (95% CI: 1.06, 3.83) increased odds of glioma than those with the lowest intake scores. The association was not substantially altered by further adjustment for BMI (2.76; 1.15-6.60).

Conclusion: In conclusion, diets with high anti-inflammatory and low inflammatory nutrient contents are recommended to prevent glioma.
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http://dx.doi.org/10.1016/j.clnu.2019.02.013DOI Listing
February 2020

Egg Consumption and Risk of Upper Aero-Digestive Tract Cancers: A Systematic Review and Meta-Analysis of Observational Studies.

Adv Nutr 2019 07;10(4):660-672

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute.

Limited data are available that summarize the relation between egg intake and the risk of upper aero-digestive tract (UADT) cancers. This systematic review and meta-analysis was conducted to investigate the association between egg intake and the risk of UADT cancers. Medline/PubMed, ISI web of knowledge, EMBASE, Scopus, and Google Scholar were searched using relevant keywords. Observational studies conducted on humans investigating the association between egg consumption and the risk of UADT cancers were included. Overall, 38 studies with a total of 164,241 subjects (27, 025 cases) were included. Based on 40 effect sizes from 32 case-control studies, we found a 42% increased risk of UADT cancers among those with the highest egg consumption (ranging from ≥1 meal/d to ≥1 time/mo among studies) compared to those with the lowest intake (ranging from 0-20 g/d to never consumed among studies) (overall OR: 1.42; 95% CI: 1.19, 1.68; P < 0.001). However, this association was only evident in hospital-based case-control (HCC) studies (OR = 1.50; 95% CI: 1.34, 1.68; P < 0.001 for 'oropharyngeal and laryngeal cancer' and OR: 1.27; 95% CI: 1.08, 1.50; P = 0.004 for esophageal cancer) and not in population-based case-control (PCC) studies (OR = 1.25; 95% CI: 0.59, 2.67; P = 0.56 for 'oropharyngeal and laryngeal cancer' and OR: 1.29; 95% CI: 0.92, 1.81; P = 0.13 for esophageal cancer). In addition, the association was not significant in prospective cohort studies (overall OR: 0.86; 95% CI: 0.71, 1.04; P = 0.11). Considering individual cancers, a positive association was observed between the highest egg consumption, compared with the lowest, and risk of oropharyngeal (OR: 1.88; 95% CI: 1.61, 2.20; P < 0.001), laryngeal (OR: 1.83; 95% CI: 1.45, 2.32; P < 0.001), oral & pharyngeal & laryngeal (OR: 1.37; 95% CI: 1.12, 1.67; P < 0.001), and esophageal cancers (OR: 1.28; 95% CI: 1.10,1.48; P = 0.001). We also found an inverse association between egg intake and the risk of oral cancer (OR: 0.78; 95% CI: 0.62, 0.99; P = 0.04). In conclusion, high egg consumption (ranging from ≥1 meal/d to ≥1 time/mo among studies) was associated with increased risk of UADT cancers only in HCC studies but not in PCC or prospective cohort studies. PROSPERO registration number: CRD42018102619.
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http://dx.doi.org/10.1093/advances/nmz010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628841PMC
July 2019

Egg Consumption in Relation to Glioma: A Case-Control Study.

Nutr Cancer 2019 29;71(1):41-49. Epub 2018 Dec 29.

b Department of Community Nutrition, School of Nutritional Sciences and Dietetics , Tehran University of Medical Sciences , Tehran , Iran.

Background And Aims: Data on the link between egg consumption and brain tumors are limited. The objective of this study was to investigate the association between egg consumption and odds of glioma in Iranian adults.

Methods: In this hospital-based case-control study, 128 newly-diagnosed cases of glioma and 256 age- and sex-matched controls were enrolled from hospitals. Patients with pathologically confirmed glioma (without any other cancers) were considered eligible. We collected data on dietary intakes, including egg consumption, using a 126-item validated FFQ. Egg consumption was computed from all foods containing this food as their ingredients. Participants were categorized into tertiles of egg consumption. Conditional logistic regression was used to examine the association between egg consumption and glioma.

Results: After adjustment for age, sex and energy intake, individuals in the middle tertile of egg consumption were 58% (OR 0.42; 95% CI 0.24, 0.73) less likely to have glioma compared with those in the lowest tertile. Further adjustment for other potential confounders strengthened the association; such that participants with the greatest consumption of egg intake were 62% (0.38; 0.18, 0.76) less likely to have glioma compared with those with the lowest consumption. Additional controlling for dietary intakes did not change the association significantly (0.39; 0.18, 0.85).

Conclusion: We found an inverse association between egg consumption at the amount of almost 2 eggs/week and odds of glioma. Further studies are required to examine this association.
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http://dx.doi.org/10.1080/01635581.2018.1540712DOI Listing
May 2020

Dairy intake and acne development: A meta-analysis of observational studies.

Clin Nutr 2019 06 8;38(3):1067-1075. Epub 2018 May 8.

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Background & Aims: In the past, some observational studies have been carried out on the relationship between milk and dairy intake and risk of acne occurrence; however, their results were conflicting. This study is a meta-analysis and dose-response analysis designed to evaluate the relationship between milk and dairy products and acne development.

Materials & Methods: Data of the study were searched and collected from Pubmed/Medline, Scopus, Web of Science, and Embase databases. Study design, sex, age, exposure (i.e. dairy, milk, yogurt, cheese), dietary assessment method, acne ascertainment, total sample size, number of total subjects and cases in each category of exposure intake, OR, RR and PR with 95% CI in each category of exposure intake and adjusted variables were extracted.

Results: Highest compared with lowest category of dairy (OR: 2.61, 95% CI: 1.20 to 5.67), total milk (OR: 1.48, 95% CI: 1.31 to 1.66), low-fat milk (OR: 1.25, 95% CI: 1.10 to 1.43) and skim milk (OR: 1.82, 95% CI: 1.34 to 2.47) intake significantly was associated with the presence of acne. Results of dose-response analysis revealed a significant linear relationship between dairy, whole milk and skim milk and risk of acne and nonlinear association between dairy, milk, low-fat milk and skim milk intake and acne.

Conclusion: In this meta-analysis we found a positive relationship between dairy, total milk, whole milk, low-fat and skim milk consumption and acne occurrence. In contrary, no significant association between yogurt/cheese and acne development was observed.
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http://dx.doi.org/10.1016/j.clnu.2018.04.015DOI Listing
June 2019

Glomerular Hyperfiltration as Predictor of Cardiometabolic Risk Factors among Children and Adolescents: The Childhood and Adolescence Surveillance and Prevention of Adult-V Study.

Int J Prev Med 2018 19;9:33. Epub 2018 Mar 19.

Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: The prevalence of glomerular hyperfiltration and chronic kidney disease is increasing worldwide in parallel with obesity hypertension epidemic. The effect of increases in glomerular filtrations (GFR) in children with metabolic syndrome has not been studied. The purpose of the present study is to investigate the relationship between GFR and cardiometabolic risk factors in a large sample of pediatric population.

Methods: In this nationwide survey, 3800 participants were selected by cluster random sampling from 30 provinces in Iran. Anthropometric measures, biochemical, and clinical parameters were measured. We also measured estimated GFR (eGFR) using the recently modified Schwartz equations and other known cardiometabolic risk factors such as elevated total cholesterol, high low-density lipoprotein cholesterol (LDL-C), and obesity.

Results: The response rate was 91.5% ( = 3843). The mean and standard deviation (SD) (Mean ± SD) of eGFR for girls, boys, and total population were 96.71 ± 19.46, 96.49 ± 21.69, and 96.59 ± 20 ml/min/1.73 m, respectively. Overall, 38.7% of the participants did not have any cardiometabolic risk factor. In multivariate models, the risk of elevated systolic blood pressure (BP) (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 1.08-2.02), elevated diastolic BP (OR: 1.48; 95% CI: 1.08-2.02), elevated LDL-C (OR: 1.35; 95% CI: 1.07-1.70), and obesity (OR: 1.70; 95%CI: 1.24-2.33) were significantly higher in participants with higher eGFR level than those with the lower level but not with low level of high-density lipoprotein cholesterol (OR: 0.72; 95% CI: 0.60-0.88).

Conclusions: This study demonstrates an association between glomerular hyperfiltration and obesity-related hypertension in a large sample of the Iranian pediatric population, independently of other classical risk factors.
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http://dx.doi.org/10.4103/ijpvm.IJPVM_38_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869957PMC
March 2018