Bilateral inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome: A reappraisal.

Cushing's syndrome (CS) is a rare disorder, once exogenous causes have been excluded. However, when diagnosed, the majority of cases are adrenocorticotropic hormone (ACTH)-dependent, of which a substantial minority are due to a source outside of the pituitary, ectopic ACTH syndrome (EAS). Differentiating among pituitary-dependent CS, Cushing's disease (CD) and an ectopic source can be problematic. Because non-invasive tests in the evaluation of CS patients often lack adequate sensitivity and specificity, bilateral inferior petrosal sinus sampling (BIPSS), a minimally invasive procedure performed during the investigation of ACTH-dependent CS, can be extremely helpful. BIPSS is considered to be the gold standard for differentiating CD from the EAS. Furthermore, although such differentiation may indeed be challenging, BIPSS is itself a complex investigation, especially in recent times due to the widespread withdrawal of corticotrophin-releasing hormone and its replacement by desmopressin. We review current published data on this investigation and, in the light of this and our own experience, discuss its appropriate use in diagnostic algorithms.

Causal effect of serum 25 hydroxyvitamin D concentration on cardioembolic stroke: Evidence from two-sample Mendelian randomization.

BACKGROUND AND AIMS: The putative association between serum 25-hydroxyvitamin D concentration [25(OH)D] and the risk of cardioembolic stroke (CES) has been examined in observational studies, which indicate controversial findings. We performed Mendelian randomization (MR) analysis to determine the causal relationship of serum 25(OH)D with the risk of CES. METHODS AND RESULTS: The summary statistics dataset on the genetic variants related to 25(OH)D was used from the published GWAS of European descent participants in the UK Biobank, including 417,580 subjects, yielding 143 independent loci in 112 1-Mb regions. GWAS summary data of CES was obtained from GIGASTROKE Consortium, which included European individuals (10,804 cases, 1,234,808 controls). Our results unveiled a causal relationship between 25(OH)D and CES using IVW [OR = 0.82, 95% CI: 0.67-0.98, p = 0.037]. Horizontal pleiotropy was not seen [MR-Egger intercept = 0.001; p = 0.792], suggesting an absence of horizontal pleiotropy. Cochrane's Q [Q = 78.71, p-value = 0.924], Rucker's Q [Q = 78.64, p-value = 0.913], and I2 = 0.0% (95% CI: 0.0%, 24.6%) statistic suggested no heterogeneity. This result remained consistent using different MR methods and sensitivity analyses, including Maximum likelihood [OR = 0.82, 95%CI: 0.67-0.98, p-value = 0.036], Constrained maximum likelihood [OR = 0.76, 95%CI: 0.64-0.90, p-value = 0.002], Debiased inverse-variance weighted [OR = 0.82, 95%CI: 0.68-0.99, p-value = 0.002], MR-PRESSO [OR = 0.82, 95%CI 0.77-0.87, p-value = 0.022], RAPS [OR = 0.82, 95%CI 0.67-0.98, p-value = 0.038], MR-Lasso [OR = 0.82, 95%CI 0.68-0.99, p-value = 0.037]. CONCLUSION: Our MR analysis provides suggestive evidence that increased 25(OH)D levels may play a protective role in the development of cardioembolic stroke. Determining the role of 25(OH)D in stroke subtypes has important clinical and public health implications.

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.

Severity of adipose tissue dysfunction is associated with progression of pre-diabetes to type 2 diabetes: the Tehran Lipid and Glucose Study.

BACKGROUND: The association of prediabetes (Pre-DM) regression and progression with visceral adiposity index (VAI) and adipose tissue dysfunction (ATD) remains to be investigated. METHODS: The present cohort study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS) on 1458 Pre-DM cases (aged ≥ 21 years) who were followed for nine years. VAI was estimated based on waist circumference, body mass index, triglycerides, and high-density lipoprotein cholesterol. ATD status (i.e., absent, mild-moderate, and severe) was defined based on the age-stratified cutoff values of VAI. Multinomial logistic regression models with adjustment of potential confounders were used to estimate the chance of Pre-DM regression to normoglycemia or progression to T2D across ATD status. RESULTS: During the study follow-up, 39.0% of the participants developed T2D, and 37.7% returned to normoglycemia. Compared to mild-moderate ATD, Pre-DM subjects with severe ATD had a higher risk of developing T2D by 45% (OR = 1.45, 95% CI = 11.08-1.93). Severe ATD was also associated with a decreased chance of returning to normoglycemia by 26% (OR = 0.74, 95% CI = 0.55-0.99). Participants with severe ATD had significantly higher fasting (overall mean = 111, 95% CI = 109-112 vs. 106, 95% CI = 105-108 mg/dL) and 2h-serum glucose (overall mean = 165, 95% CI = 161-168 vs. 153, 95% CI = 149-156 mg/dL) concentrations over time. CONCLUSION: Severe ATD was associated with an elevated risk of developing T2D and longitudinal poor-glycemic controls in Pre-DM subjects. ATD may be a simple and useful index for detecting subjects at a higher risk of Pre-DM progression to T2D, allowing for timely intervention strategies.

Dietary determinants of healthy/unhealthy metabolic phenotype in individuals with normal weight or overweight/obesity: a systematic review.

Objectives: Nutritional factors are amongst the major determinants in the onset and development of obesity and metabolic complications. Nevertheless, the dietary determinants of metabolic health are not completely elucidated. The aim of this systematic review is to investigate nutritional and dietary factors that may contribute to metabolic heterogeneity in individuals with obesity or normal weight. Methods: A literature search was performed in PubMed, Scopus, EMBASE, and google scholar databases until August 2021, to locate studies that examined metabolic health and its association with intakes of specific foods or food groups, nutrient intakes or status, as well as adherence to certain dietary patterns. Two researchers had independently screened titles and abstracts, examined full-text studies, conducted data extraction, and evaluated their quality using the Newcastle-Ottawa Scale. Results: Twenty-seven studies, with a total of 39518 subjects, were included. Of these studies, 11 articles evaluated the association between different dietary patterns and metabolic phenotypes, while 15 had investigated the association of single food/nutrients intakes or nutrient status with metabolic phenotype, and one paper evaluated the association of dietary inflammatory index with metabolic health. The findings of these studies propose that healthy dietary patterns such as the Mediterranean pattern, Dietary Approaches to Stop Hypertension, and population-derived patterns (such as the "Healthy" and "Fruit and vegetable" patterns) were associated with higher odds of the metabolically healthy phenotype. Higher intakes of fruits, vegetables, dairy products, coffee/tea, vitamin D, magnesium, and flavonoids, were suggested to lower the risk of developing metabolically unhealthy phenotype, while, higher consumption of saturated fat, carbohydrate and sugar-sweetened beverages, fast foods, organ meats, and a pro-inflammatory diet increased the risk. Conclusion: Results from published studies, which were mostly cross-sectional, suggest that higher adherence to unhealthier dietary patterns, characterized by the consumption of refined and processed foods, was associated with a lower likelihood of having a healthy metabolic phenotype, while the opposite was observed for healthier dietary patterns. Findings may be used in developing nutritional strategies aimed at improving metabolic health in the population.

Cumulative burden and trajectories of body mass index and blood pressure from childhood and carotid intima-media thickness in young adulthood.

There are significant gaps in understanding of the association between levels and rate of change of body mass index (BMI) and blood pressure (BP) at different ages during childhood and carotid intima-media thickness (CIMT) in adulthood. We investigated the association between trajectories of BMI and BP from childhood to adulthood and adult CIMT among Iranian participants in the Tehran Lipid and Glucose Study (TLGS) cohort. A total of 1334 participants (692 men), from the TLGS cohort (1999-2018) with repeated measurements of BMI and BP (2-6 times) from childhood (3-18 years) to young adulthood (20-40 years) were selected. Trajectory parameters included levels and linear slopes of BMI and BP growth curve models, and cumulative burden defined as the area under those curves (AUC). After adjusting for confounders, AUC of BMI and diastolic blood pressure (DBP) were significantly associated with high CIMT in adulthood, with the standardized odds ratios (OR) and 95% confidence interval (95% CI) of 1.35 (1.12-1.62) and 1.27 (1.01-1.60), respectively. Associations between level-independent slopes of BMI and adult CIMT were significantly positive (ORs: 1.27 to 1.26) during childhood ages (3-18 years). Further, levels of BMI (ORs: 1.23 to 1.29) and DBP (ORs: 1.25 to 1.33) during the ages of 13-18 and 11-17 years, respectively, were significantly associated with CIMT in adulthood (all P < 0.05). The cumulative burden of BMI and DBP was associated with CIMT in adulthood. Adolescence is a crucial period for high CIMT, which has implications for early prevention of atherosclerosis.

Comparing Effects of Bariatric Surgery on Body Composition Changes in Metabolically Healthy and Metabolically Unhealthy Severely Obese Patients: Tehran Obesity Treatment Study (TOTS).

BACKGROUND: Among two popular obesity phenotypes, metabolically healthy severely obese (MHSO) and metabolically unhealthy severely obese (MUSO), it is important to clarify whether or not those with MHSO phenotype would benefit from bariatric surgery in terms of an improvement in body composition parameters. METHODS: A prospective cohort was conducted on a total of 4028 participants (1404 MHSO and 2624 MUSO) who underwent bariatric surgery; MHSO was defined as having abnormalities in none or one of these four parameters: systolic blood pressure and/or diastolic blood pressure, triglycerides, fasting plasma glucose, and high-density lipoprotein. Otherwise, the definition of MUSO was met. Body composition analysis was performed at the baseline and 6-, 12-, 24-, and 36-month post-surgery using bioelectrical impedance analyzer. RESULTS: Both phenotypes showed a significant decrease in fat mass (FM) and fat-free mass (FFM) and a significant increase in EWL% and TWL% (Ptrend < 0.05). FFM, FM%, and excess weight loss (EWL%) were significantly different between the two phenotypes (Pbetween < 0.05) during the follow-up. Multivariate linear regression demonstrated that compared to MUSO patients, MHSO individuals experienced a greater increase in total weight loss (TWL%) and EWL% at 12- and 24-month and in EWL% at 36-month post-surgery and also a lower decrease in the FFML/WL% after 12 months. CONCLUSION: Despite a lower decrease of FFML/WL% and a greater increase in TWL and EWL in MHSO phenotype at some time points, there were no clinically significant differences between the study groups in terms of body composition changes throughout the follow-up period.

A Comparative Analysis of Safety and Efficacy of Bariatric Surgery During the COVID-19 Pandemic and Pre-Pandemic Period: Insights from the Tehran Obesity Treatment Study.

BACKGROUND: The COVID-19 pandemic has raised global health concerns and posed challenges for postoperative follow-up care for patients undergoing bariatric surgery due to social distancing rules. METHODS: This was a cohort study on patients with morbid obesity who underwent bariatric surgery and had been enrolled in Tehran Obesity Treatment Study. Patients who had surgery between March 2020 and March 2021 were classified as those undergoing the procedure amid the COVID-19 pandemic, while those who had surgery between March 2017 and March 2018 were categorized as the pre-pandemic group. RESULTS: The study included 982 patients in the pre-COVID-19 pandemic group and 602 patients in the COVID-19 pandemic group, with mean ages of 39.61 and 39.51 years, respectively. After adjusting for preoperative body mass index (BMI) and surgery type, the patients who underwent surgery during the COVID-19 pandemic demonstrated comparable results to the pre-COVID-19 group in terms of total weight loss %, excess weight loss %, BMI reduction, and fat mass reduction during the 12-month postoperative period. Additionally, the rate of complications with a grade≥III based on the Clavien-Dindo classification was significantly lower in patients who underwent surgery during the COVID-19 pandemic. Notably, there were no deaths reported in either group. CONCLUSION: Despite social isolation and unfavorable lifestyle modifications, bariatric surgery-induced weight loss after one year was the same in patients undergoing the procedure either before or after the implementation of social distancing measures. More research is needed to analyze the influence of the COVID-19 pandemic on the long-term outcomes of bariatric surgery.

Association between BMI trajectories from childhood to early adulthood and the carotid intima-media thickness in early adulthood: Tehran lipid and glucose study.

BACKGROUND AND AIMS: Childhood and adolescence overweight/obesity is an important predictor of obesity and increased long-term cardiometabolic abnormalities in adulthood. In this study, we aimed to investigate the association of body mass index (BMI) and waist circumference (WC) trajectories among children and adolescents with adulthood carotid intima-media thickness (cIMT) as a determinant of subclinical atherosclerosis. METHODS: In this prospective cohort study, 1265 participants aged 3 to 18 were followed up for 18 years. By using Latent Class Growth Analysis, three groups of BMI and WC trajectory were defined; low stable, moderate-increasing, and high-increasing. Linear and logistic regression analysis were used to investigate the association of each lifetime BMI and WC trajectory group with cIMT. RESULTS: Although the high-increasing BMI trajectory group was significantly associated with higher cIMT (ß=0.0464, P < 0.001), moderate-increase was not (ß=0.0096, P = 0.102); in reference to the low-stable BMI trajectory group. Among WC trajectory groups, both moderate- (ß=0.0177, P = 0.006) and high-increasing (ß=0.0533, P < 0.001), in reference to the low-stable group, were significantly associated with higher cIMT. The results did not change after adjustment for baseline BMI. The ORs of high-increasing BMI, moderate-increasing WC, and high-increasing WC trajectories were 3.24, 1.92, and 3.29, respectively for high cIMT. CONCLUSION: Our study resulted that a high-increasing trajectory of childhood BMI and moderate- and high-increasing trajectories of childhood WC are associated with higher cIMT and higher risk of high-cIMT. Regular monitoring and screening of BMI and WC trajectory from childhood may improve identifying individuals with high risks of cardiovascular disease, more accurately.

BMI category-specific waist circumference thresholds based on cardiovascular disease outcomes and all-cause mortality: Tehran lipid and glucose study (TLGS).

BACKGROUND: Waist circumference (WC), a representative of abdominal visceral fat, is strongly associated with cardiovascular disease (CVD) and its outcomes. We aimed to define body mass index (BMI)-specific WC thresholds as predictors of CVD and all-cause mortality. METHODS: In this prospective cohort study in the context of the Tehran Lipid and Glucose Study (TLGS), a total of 3344 men and 4068 women were followed up for 18 years. Based on BMI, the participants were categorized into three groups: BMI < 25, 25 < BMI < 30, and BMI > 30. In each BMI category, sex-specific WC thresholds were estimated by the maximum value of Youden's index to predict based on incident CVD events and all-cause mortality prediction. RESULTS: Overall 667 and 463 CVD events (the incidence rate of 3.1 to 4.5 in men and 1.1 to 2.6 in women per 1,000 person-years within BMI categories) and 438 and 302 mortalities (the incidence rate of 2.1 to 2.7 in men and 1.2 to 1.4 in women per 1,000 person-years within BMI categories) were recorded in men and women, respectively. WC thresholds in the BMI categories of < 25, 25-30, and BMI > 30 kg/m2 with regard to CVD events were 82, 95, and 103 cm in men and 82, 89, and 100 cm in women, and regarding all-cause mortality, the respective values were 88, 95, and 103 cm in men and 83, 90, and 99 cm among women. CONCLUSION: BMI-specific WC thresholds observed here can help to better identify individuals at high risk of developing CVDs.

The mediating role of bariatric surgery in the metabolic relationship between parathyroid hormone and 25-hydroxyvitamin D.

Vitamin D metabolism is altered in obese individuals. Our findings indicated that in patients with severe obesity, a relatively low 25(OH)D concentration was required to suppress PTH. The PTH inflection point increased following surgery-induced weight loss, highlighting 25(OH)D different regulation mechanisms in patients with obesity. INTRODUCTION: An optimal and sufficient concentration of 25-hydroxyvitamin D (25(OH)D) has been suggested as the level required to maximally suppress intact parathyroid hormone (iPTH). We evaluated the role of surgery-induced weight loss in determining the threshold(s) of 25(OH)D required to suppress iPTH. METHODS: This study was conducted in the framework of the Tehran Obesity Treatment Study (TOTS). We prospectively analyzed 687 patients with severe obesity who participated in the TOTS and underwent bariatric surgery from March 2013 to March 2019. The patients were followed for 1 year after surgery. Anthropometric parameters and serum levels of iPTH, 25OHD, phosphorous, and calcium were measured. Nonlinear and piecewise linear regression was used to evaluate the relationship between 25(OH)D and iPTH and to determine the 25(OH)D-suppression point at which iPTH was maximally suppressed. RESULTS: Body mass index was 44.6 kg/m2 at the baseline and decreased to 29.7 kg/m2 1 year after surgery (P < 0.05). Before the surgery, iPTH and 25(OH)D showed an exponential relationship; iPTH began to decrease rapidly at 25(OH)D concentration of 12 ng/mL, reaching maximal suppression at 30 ng/mL. However, the relationship between 25(OH)D and iPTH was non-exponential 1 year after surgery. The piecewise linear regression model revealed the 25(OH)D concentration of 21 ng/mL as the inflection point following surgery-induced weight loss. CONCLUSION: In patients with severe obesity, PTH was suppressed at a relatively lower concentration of 25(OH)D; this threshold increased following surgery-induced weight loss. These findings suggest a role for bariatric surgery in regulating 25(OH)D metabolism in patients with obesity.

Mental health and quality of life in different obesity phenotypes: a systematic review.

OBJECTIVES: It has been suggested that obesity phenotypes are related to mental health problems and health-related quality of life (HRQoL). However, there is no certain consensus. This systematic review aimed to evaluate the association between different obesity phenotypes with common psychiatric symptoms and HRQoL. METHODS: Electronic databases i.e. PubMed, Scopus, EMBASE, and google scholar were searched until September 2021, to identify studies that investigated associations between the obesity phenotypes with psychiatric symptoms and/or mental and physical HRQoL. Two researchers independently checked titles and abstracts, evaluated full-text studies, extracted data, and appraised their quality using the Newcastle-Ottawa Scale. RESULTS: Eighteen studies, with a total of 3,929,203 participants, were included. Of the studies included in this systematic review, 10 articles evaluated the association between obesity phenotypes and psychiatric symptoms, while six papers investigated the association between HRQoL and obesity phenotypes, and two studies assessed both. As a whole, the findings of these studies suggest that obese individuals with a favorable metabolic profile have a slightly higher risk of mental health problems and poor quality of life, however, the risk becomes larger when obesity is combined with an adverse metabolic profile. So, metabolically healthy obesity may not be a completely benign condition in relation to mental disorders and poor quality of life. CONCLUSION: According to published research, obesity is likely to increase the risk of mental health problems and poor quality of life when metabolic disturbances are present.

Transition from metabolically healthy to unhealthy overweight/obesity and risk of cardiovascular disease incidence: A systematic review and meta-analysis.

AIMS: Discrepant results have been demonstrated regarding the cardiovascular (CV) risk of populations with metabolically healthy overweight/obesity (MHO) who were transitioned into metabolically unhealthy states. So, the objective of this systematic review and meta-analysis was to estimate the risk of cardiovascular diseases (CVD) incidence in individuals with transitional MHO phenotype. DATA SYNTHESIS: A literature review was done in PubMed, Scopus, EMBASE, and google scholar databases. Pooled HRs for all fatal and nonfatal CV events were computed using random-effect models for transitional MHOs in general as well as for each sex subgroup separately. This systematic review and meta-analysis included a total of 7 prospective observational studies with a total of 7,720,165 participants, published between 2018 and 2020. The mean follow-up duration of participants was 11.7 (5.5) years. Overall, the transitional MHO individuals had a significant risk of CVD incidence [HR = 1.42, 95% CI (1.24-1.60)]. In addition, in both male and female subgroups, unstable MHO phenotype demonstrated a significant CVD risk and HRs for incident CVD in males and females were 1.51 (1.07-1.96) and 1.71 (1.08-2.34), respectively. CONCLUSION: Transition from MHO to unhealthy state throughout follow-up elevated the risk of CVD in both male and female groups. This can explain the association between MHO and incidence of CV events especially with longer follow up period. REGISTRATION CODE IN PROSPERO: CRD42021270225.

Anemia After Sleeve Gastrectomy and One-Anastomosis Gastric Bypass: An Investigation Based on the Tehran Obesity Treatment Study (TOTS).

BACKGROUND: Bariatric surgery has been associated with iron, folate, and vitamin B12 deficiencies, which can lead to anemia. This study compares the incidence of anemia between sleeve gastrectomy (SG) and one-anastomosis gastric bypass (OAGB). METHODS: Patients from a prospectively collected database of patients with morbid obesity undergoing a primary bariatric procedure from April 2013 to September 2018 were included. Statistical analysis was performed using the general estimation equation. Patients were followed for 6, 12, 24, and 36 months post-surgery. RESULTS: The present study included 2618 patients, of whom 72.3% underwent SG and 27.6% underwent OAGB. The majority of the study population were women (75.7%), and the mean age of the participants was 39.5 ± 11.7 years. At the end of the follow-up, the excess weight loss percentage was 66.15 in the SG group and 75.41 in the OAGB group (P < 0.05). The incidence of anemia at 12-, 24-, and 36-month was 16.2, 19.7, and 24.3% in the SG group and 28.4, 37.6, and 56.5% in the OAGB group, showing significantly higher incidence in the OAGB than the SG group ([Formula: see text] < 0.001). However, there was no significant difference between the SG and OAGB groups regarding the incidence of iron and vitamin B12 deficiency. CONCLUSIONS: The patients undergoing bariatric surgery, especially OAGB, should be closely monitored post-surgery regarding the incidence of anemia, and supplementation in developing countries could be continued even after the first year.

Association of childhood obesity phenotypes with early adulthood Carotid Intima-Media Thickness (CIMT): Tehran lipid and glucose study.

BACKGROUND AND AIMS: Over the past few years, obesity and metabolic syndrome prevalence among children and adolescence have an increasing trend. This study aims to investigate the association of obesity phenotypes during childhood and adolescence with early adulthood carotid intima-media thickness (CIMT). METHODS AND RESULTS: Participants were divided into four obesity phenotypes: Metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Participants were followed for 18 years. Multivariate-adjusted Risk Ratios (RRs) were calculated for high CIMT (≥95% percentile) incidence. In this cohort study 1220 children and adolescents with the average age of 10.9 ± 4.0 years were included. CIMT values had a significantly increasing trend from MHNW to MUO group (p for trend<0.001). Individuals with normal weight status, even with an unhealthy metabolic profile did not have higher risk of high CIMT. Similarly, Children with obesity but healthy metabolic status was not at higher risk. On the other hand, MUO phenotype during childhood was associated with increased risk of high CIMT in early adulthood (RR = 2.13, 95%CI (1.02-4.48)). This association became insignificant for all obesity phenotypes after adjusting for adulthood BMI. CONCLUSION: Adulthood CIMT has an increasing trend based on childhood and adolescence obesity phenotypes from MHNW to MUO. Children with MUO phenotype was the only ones that had an increased risk of high CIMT incidence in early adulthood.

Association of cumulative excess weight and waist circumference exposure with transition from metabolically healthy obesity to metabolically unhealthy.

BACKGROUND AND AIMS: The association between obesity severity and duration with the transition from metabolically healthy obese/overweight (MHO) phenotype to metabolically unhealthy obese (MUO) phenotype is not well understood. METHODS AND RESULTS: This study includes the Tehran Lipid and Glucose Study participants who were initially classed as MHO. Cumulative excess weight (CEW) and cumulative excess waist circumference (CEWC) scores, which represent the accumulation of body mass index and waist circumference deviations from expected values over time (kg/m2 ∗ y and cm ∗ y, respectively), were calculated until the transition from MHO to MUO or the end of follow-up. The sex-stratified association of CEW and CWEC with the transition from MHO to MUO was investigated by time-dependent Cox models, adjusting for confounders. Out of 2525 participants, 1732 (68.5%) were women. During 15 years of follow-up, 1886 (74.6%) participants transitioned from MHO to MUO. A significant association was found between CEW and CEWC quartiles with the development of MUO among women participants (fully adjusted hazard ratios in the fourth quartile of CEW and CEWC [95% (CI)]:1.65 [1.37-1.98] and [95% CI]: 1.83 [1.53-2.19]). There was no significant association between CEW and CEWC with the MHO transition to MUO among men participants. CONCLUSION: Over 15 years of follow-up in TLGS, general and central obesity accumulation was associated with the increased transition from MHO to MUO among women participants. More research with a larger sample size is needed to confirm and explain why the results are different for men and women.

The association of the age, period, and birth cohort with 15-year changes in body mass index and waist circumference in adults: Tehran lipid and glucose study (TLGS).

OBJECTIVE: To examine the association of age, period, and birth cohort with body mass index (BMI) and waist circumference (WC) changes among the participants of the Tehran Lipid and Glucose Study from 1999 to 2015. METHODS: This prospective cohort study included 4895 participants aged ≥20 years (41.3% men), who were divided into twelve gender stratified groups, having a ten-year age difference between them. Analyses were conducted to explicitly assess the association of age vs. period on BMI and WC changes. In addition, we evaluated BMI and WC changes among different birth cohorts. RESULTS: Upon 15 years of follow-up, the mean BMI of men and women increased from 26.0 ± 3.9 to 27.5 ± 4.3 kg/m2 and from 27.5 ± 4.8 to 29.9 ± 5.4 kg/m2 (P trend < 0.001), and this trend was accompanied by an increase in WC from 88.8 ± 10.9 to 97.8 ± 10.4 cm and from 87.3 ± 12.4 to 95.8 ± 12.1 cm, respectively (P trend < 0.001). Men and women in all age cohorts tended to have a rise in their BMI and WC with aging throughout the follow-up period. For men, this trend was more prominent in younger birth cohorts at phase III for BMI and at phases III and V for WC (indicating a significant negative association with birth cohort). For women, this trend was more prominent in older birth cohorts at both phases III and V for BMI and WC (indicating a significant positive association with the birth cohort). CONCLUSION: The rise in BMI and WC was strongly associated with age in both sexes. The men born in the recent birth cohorts and the women born in earlier birth cohorts had the most alarming BMI and WC trends. More efforts must be spent on obesity prevention policies, especially for younger men.

The effect of bariatric surgery in comparison with the control group on the prevention of comorbidities in people with severe obesity: a prospective cohort study.

BACKGROUND: Obesity is a global health priority, particularly in developing countries. The preventive effect of bariatric surgery against obesity-related diseases in the developing countries of the Middle East and North Africa region, where type 2 diabetes mellitus (T2DM), hypertension (HTN), and dyslipidemia prevail, has not been examined. METHOD: Severely obese participants who underwent bariatric surgery were compared with their counterparts who underwent no intervention. These patients had been followed up in two prospective cohort studies for three years. We here determined the incidence of new-onset T2DM, HTN, and dyslipidemia and reported absolute and relative risks for the incidence of these comorbidities in the two groups. RESULTS: In this study, 612 participants in the bariatric surgery group were compared with 593 participants in the control group. During the follow-up period, T2DM developed in eight (2.9%) people in the surgery group and 66 (15.0%) people in the control group (P < 0.001). New-onset HTN and dyslipidemia showed significantly lower frequencies in the surgery group compared to the control group (4 (1.8%) vs. 70 (20.4%) and 33 (14.3%) vs. 93 (31.5%), respectively). Regarding a less favorable metabolic profile in the surgery group at the baseline, the relative risk reductions associated with bariatric surgery were 94, 93, and 55% for the development of T2DM, HTN, and dyslipidemia, respectively. CONCLUSION: The risk reduction of obesity-related comorbidities after bariatric surgery should be considered in the decision-making process for public health in the region, which bariatric surgery could result in the prevention of comorbidities.

Association of obesity phenotypes in adolescents and incidence of early adulthood type 2 diabetes mellitus: Tehran lipid and glucose study.

OBJECTIVE: Obesity and metabolic syndrome, which has an increasing prevalence among adolescence, are associated with metabolic abnormalities. This study investigates the role of adolescent obesity phenotypes in predicting the incidence of early adulthood type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Participants were divided into four obesity phenotypes: Metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). Multivariate-adjusted hazard ratios (HRs) were calculated for T2DM incidence. RESULTS: In this cohort study, 2306 Tehranian adolescents with an average age of 15.1 ± 2.4 years were included. The median (IQ 25-75) follow-up was 15.5 (12.8-17.1) years and the median (IQ 25-75) age of participants at the end of follow-up was 30 (26-32) years old. The incidence rate of T2DM during the early adulthood was [1.37 (95% CI: 0.89-2.10)] and [3.18 (95% CI: 2.44-4.16)] per 1000 person per year in boys and girls, respectively. MHO phenotype was not associated with an increased risk of T2DM for both sexes. Adjusted HRs for MUO were [4.30 95% CI (1.48-12.43)] and [3.39 95% CI (1.78-6.45)] in boys and girls, respectively. MUNW phenotype was associated with an increased risk of T2DM only in boys. After adjustment for adulthood BMI, all the phenotypes for both sexes lost their significance, except for boys with MUNW phenotype [HR = 3.46 95% CI (1.15-10.45)]. CONCLUSIONS: Unhealthy obesity phenotypes; in contrast with MHO; had an increased risk of T2DM incidence, apart from girls with MUNW. After adjusting the adulthood BMI, all phenotypes turn insignificant, except for boys with MUNW.

Daily vitamin D3 in overweight and obese children and adolescents: a randomized controlled trial.

PURPOSE: To assess the efficacy of different doses of vitamin D3 on serum 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone(iPTH), calcium, phosphorus, and alkaline phosphatase concentrations in overweight and obese school-children. METHODS: A total of 378 children and adolescents, 6-13 years of age, with age- and sex-specific body mass index(BMI) Z-score ≥ 1(according to the World Health Organization criteria) were allocated to receive 600, 1000, and 2000 IU vitamin D3/days. 25(OH)D, iPTH, calcium, phosphorus, and alkaline phosphatase concentrations were measured at baseline, 6, and 12 months. In this intention-to-treat analysis, we fitted a linear mixed effect model involving a random effect of participants within treatment groups and fixed effects of dose, time, and their interactions. RESULTS: Mean(SD) of age and BMI Z-score were 9.3 (1.7) years and 2.55 (0.73), respectively. The median (IQR) for 25(OH)D was 11.5 (8.9), 11.7 (10.5), 12.2 (10.2) ng/mL (28.75, 29.25, and 30.50 nmol/L) at baseline and 23.1 (8.0), 25.6 (8.3), 28.6 (10.4) ng/mL (57.75, 64.00, and 71.50 nmol/L) at the end of 12 months in 600, 1000, and 2000 IU, respectively (p values for dose, time, and the interaction being < 0.0001, < 0.0001,and 0.082, respectively). Prevalence of vitamin D deficiency (< 20 ng/mL) was 80.2, 77.5, and 75.5% in 600, 1000, and 2000 IU groups at baseline, respectively, which decreased to 34, 18.4, and 7.5%, respectively, at 12 months. Patterns of iPTH, calcium, phosphorus, and alkaline phosphatase response over time did not differ significantly among groups (p values = 0.452, 0.670, 0.377, 0.895, respectively). CONCLUSIONS: Increases in 25(OH)D concentration were found with supplementation of 1000 and 2000 IU, compared with 600 IU/days, whereas there was no evidence of iPTH suppression or change in serum calcium, phosphorus, and alkaline phosphatase among children with excess weight.