Healthy Obese Individuals Research Articles

A study of cardiovascular risk among depressed obese patients

Background: Both depression and obesity are widespread problems with major public health implications. Depression and obesity are both associated with an increased risk of cardiovascular disease (CVD) and with marked impairments in the quality of life. Aim and Objective: The aim of the study is to assess the CVD risk and cardiovascular risk factors among depressed obese individuals. Materials and Methods: Fifty patients of depression whose body mass index (BMI) >30 kg/m2 and diagnosed with ICD-10 criteria of depression were selected as study group and 30 healthy obese of BMI >30 kg/m2 without depression were selected as the control group for the study. The participants were divided into two groups: obese patients with depression and healthy obese individuals without depression. Fasting venous blood sample was collected under aseptic condition to estimate fasting blood sugar, total cholesterol, and high - density lipoprotein cholesterol. Using standard mercury manometer at least two readings at 5 - min intervals, were taken to measure the blood pressure (BP) in the supine position. Both the groups were subjected to specially designed pro forma which included personal and sociodemographic details and Framingham risk assessment tool for assessing cardiovascular risk. The cardiovascular risk was assessed and compared using Framingham risk score assessment tool. Results and Conclusion: Mean age of depressed obese was 46.44 ± 10.44 years and healthy obese had 47.33 ± 10.53. Mean BMI of study group was 32.82 ± 2.53 and healthy obese had 31.76 ± 1.66. BMI was significantly associated with depression. Presence of depression in obese patients increases the chances of CVD risk. Presence of smoking, hypertension, and high cholesterol in patients with depression, increase the risk of CVD, which can be modified by healthy diet, regular exercise, and BP management with periodic blood investigation and regular medication.

Unlocking the secret of the obesity paradox in renal tumours.

The obesity paradox refers to the correlation between obesity and improved oncological outcomes in patients with advanced cancer, despite the fact that metabolically healthy obese individuals have an increased risk of developing cancer in the first place. In The Lancet Oncology, Alejandro Sanchez and colleagues 1 Sanchez A Furberg H Kuo F et al. Transcriptomic signatures related to the obesity paradox in patients with clear cell renal cell carcinoma: a cohort study. Lancet Oncol. 2019; (published online Dec 20)https://doi.org/10.1016/S1470-2045(19)30797-1 Summary Full Text Full Text PDF PubMed Scopus (81) Google Scholar investigated the transcriptomic profile of tumours within the context of the obesity paradox in patients with clear cell renal cell carcinoma (RCC). They investigated the angiogenic and immunological transcriptomic profiles of tumours and perinephric adipose tissue in patients with a normal weight (ie, with a body-mass index [BMI] 18·5–24·9 kg/m2, as per WHO's BMI categories) and in obese patients (BMI ≥30 kg/m2) in five cohorts of patients with clear cell RCC. Transcriptomic signatures related to the obesity paradox in patients with clear cell renal cell carcinoma: a cohort studyWe found aspects of the tumour microenvironment that vary by BMI in the tumour and peritumoral adipose tissue, which might contribute to the apparent survival advantage in obese patients with clear cell RCC compared with patients at a normal weight. The complex interplay between the clear cell RCC tumour and peritumoral adipose tissue microenvironment might have clinical relevance and warrants further investigation. Full-Text PDF

The Relation of Omentin-1 Levels and Some Trace Elements as a Potential Markers for Diagnosis of Prediabetic Obese Patients

Abstract The obesity is one of the most common physiological disorders, also it is linked with a variety of circumstances like hypertension, dyslipidemia, T2DM, non-alcoholic fatty liver disease, and cardiovascular diseases. The aim of this study was to check the changes and compare serum omentin-1, lipid profile (TC, TG, VLDL-C, LDL-C, and HDL-C), trace elements (Mg, Zn, Cu, Fe) and insulin resistance between the prediabetic obese patients, healthy obese, and control subjects and assess the correlation between omentin-1, lipid profile, trace elements (Mg, Zn, Cu, Fe) levels and insulin resistance in prediabetic obese patients. Correlation analysis between omentin-1 levels with the biochemical parameters in the prediabetic obese patients with WC, body mass index, FBG, Insulin, HOMA-IR, HbA1c, TG, TC, LDL-C, VLDL-C, and copper was found to be negative; while significant positive correlation of omentin-1 with HDL-C, Mg, Zn, and Fe was noticed. Omentin-1 serum concentration level decrease and insulin resistance increased in prediabetic obese patients compared to healthy obese and control individuals. Omentin-1 inversely associated with obesity and insulin resistance, therefore can be used as a biomarker for obesity related metabolic disorders.

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

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. 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. 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). 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.

Genetic scores for BMI related to metabolically unhealthy obesity in an older Chinese population.

In this study, a genetic risk score (GRS) for the body mass index (BMI) tested and built using a large sample of Chinese individuals aged at least 50years in southern China. We collected information regarding the participants' weights at 20years of age and middle age and tested the BMI-GRS effect modes. This study involved a prospective study design. The genetic data of the participants in from the Guangzhou Biobank Cohort Study and selected BMI-related single-nucleotide polymorphisms (SNPs) were used to establish the GRS. We included 13597 participants with 12 SNPs. After adjusting for covariates, the high-GRS group was 36% (95% CI: 25%-48%) and 34% (95% CI: 23%-47%) more likely of being overweight at baseline and follow-up, respectively, and 56% (95% CI: 34%-82%) and 49% (95% CI: 29%-72%) more likely of being obese at baseline and follow-up, respectively, compared with the low-GRS group (P-value for all trends <.05). The RRs for the incidences of metabolically healthy and unhealthy obese (MHO and MUO, respectively) individuals in the high-GRS group were 0.94 (95% CI: 0.65-1.35) and 1.28 (95% CI: 1.00-1.63), respectively. High-GRS participants were more likely to be overweight/obese at baseline and follow-up, and this relationship exhibited a dose-response relationship. The GRS was also associated with MUO.

Obesity: A preventable, treatable, but relapsing disease.

In 2013, the American Medical Association recognized obesity as a disease, of growing scientific, social, and political interest. In 2016 in the United States, prevalence rates of preobesity and obesity exceeded 60%. In Italy, these rates exceeded 40%. Total costs related to excess weight reached 9.3% of the U.S. gross domestic product, whereas in Italy the total annual cost of diabetes alone was estimated at 20.3 billion euros/y. The expansion of adipose tissue and visceral fat causes compression, joint stress, metabolic disorders, organ dysfunction, and increased mortality. The increase in peripheral and central fat mass is a chronic and potentially reversible process with appropriate diagnosis and treatment. Conversely, fattening can turn into a chronic relapsing form, complicated by comorbidities and cardiovascular events. The increased risk for mortality and morbidity also can affect metabolically healthy obese individuals, if the condition is underestimated, with disease progression. Due to its inaccuracy, body mass index must be replaced with body composition for the diagnosis of obesity. The chances of obesity reversibility are closely linked to improving the diagnosis and to timely nutritional interventions. Generalization and stigma hinder the treatment of obese individuals. The recognition of obesity as a disease and institutional interest can shift the focus onto obesity and not on the obese, with improvements in adherence to prevention plans. Anthropogenic factors and gut microbiota can influence human behavior and food choice, such as food addiction. Obesity has all the criteria to be recognized as a disease. Proper clinical management will lead to cost and complications savings, such as in diabetes. The aim of this review was to discuss in detail the criteria for defining primary obesity as a disease in a step-by-step manner.

Metabolic phenotypes of obese, overweight, and normal weight individuals and risk of chronic kidney disease: a systematic review and meta-analysis.

Chronic kidney disease (CKD) risk is inconsistent in the normal-weight, overweight, and obese individuals due to the heterogeneity of metabolic status. This meta-analysis aimed to examine the combined effects of body mass index (BMI) and metabolic status on CKD risk. The MEDLINE, EMBASE, and Web of Knowledge databases were systematically searched up to March 2019 to identify all eligible studies investigating the CKD risk (defined as GFR < 60 mL/min per 1.73 m2 and/or microalbuminuria or proteinuria) associated with the body size phenotypes which are known as metabolically unhealthy normal-weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight, metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO). The classification of subjects in included studies as metabolically unhealthy was based on the presence of three components of metabolic syndrome. BMI categorization was based on the criteria of included studies. The risk estimates and 95% confidence intervals (CIs) were extracted and pooled using random effects analysis. A total of 9 prospective cohort studies with 128773 participants and 4797 incident cases were included in the meta-analysis. Compared with healthy normal-weight individuals as reference, MUNW and MHO subjects showed an increased risk for CKD events with a pooled RR of 1.58 (95% CI = 1.28-1.96) in MUNW and 1.55 (95% CI = 1.34-1.79) in MHO persons. Also, MHOW was at increased risk for CKD (RR = 1.34, 95% CI = 1.20-1.51). MUHO individuals were at the highest risk for the development of CKD (RR = 2.13, 95% CI = 1.66-2.72). Individuals with metabolic abnormality, although at normal-weight, have an increased risk for CKD. Healthy overweight and obese individuals had higher risk; refuting the notion that metabolically healthy overweight and obese phenotypes are benign conditions.

ASSOCIATION OF METABOLIC HEALTH WITH VASCULAR AGE IN OBESE PATIENTS

Objective:Obesity is a significant risk factor for cardiovascular diseases. It is known there is a subgroup among obese people who have normal insulin sensitivity, lipid profile and blood pressure – these subjects are generally considered metabolically healthy obese (MHO) individuals. Vascular age i

Circulating 25-Hydroxyvitamin D Concentrations in Overweight and Obese Adults Are Explained by Sun Exposure, Skin Reflectance, and Body Composition

ABSTRACTBackgroundObese individuals are known to be at higher risk for vitamin D deficiency than normal-weight individuals. Cutaneous synthesis is a major source of vitamin D; however, objective measurements of sun exposure are lacking in this population.ObjectiveTo assess the validity of a regression model using sun exposure in lean individuals to estimate serum 25-hydroxyvitamin D [25(OH)D] in overweight and obese individuals, and to develop a prediction equation for serum 25(OH)D in overweight and obese adults.MethodsThis study was a secondary analysis of a 15-wk controlled feeding study investigating the effects of dairy consumption on body composition. Information regarding sun exposure, including day, hour, time outside, and clothing, were self-assessed in sun exposure diaries. Personal sun exposure energy (joules) was assessed by downloading time-specific ultraviolet B energy data from climate stations. Skin reflectance was measured using a Minolta 2500d spectrophotometer. Dietary intake of vitamin D was known. Serum 25(OH)D concentration was measured by radioimmunoassay. Body composition was determined from whole-body dual energy x-ray absorptiometry and computed tomography scans.ResultsSun exposure was positively related to serum 25(OH)D (r = 0.26; P ≤ 0.05) and inversely related to total fat mass, android fat, and BMI (r = −0.25, −0.30, and −0.32, respectively). The modified Hall model significantly overestimated serum 25(OH)D in overweight and obese adults by 27.33–80.98 nmol/L, depending on the sun exposure calculation. A new regression model was developed for overweight and obese persons that explained 29.1% of the variance in postintervention 25(OH)D concentrations and included sun exposure, skin reflectance, total fat mass, total lean mass, and intra-abdominal adipose tissue as predictors.ConclusionMajor determinants of serum 25(OH)D concentration in healthy overweight and obese individuals include sun exposure, skin reflectance, and adiposity. Addition of adiposity terms to the prior model significantly improved predictive ability in overweight and obese men and women. (clinicaltrials.gov: NCT00858312)

276-OR: Rethinking Metabolically Healthy Obesity: What Is the Underlying Risk?

Introduction: Type 2 diabetes (T2D) is a multifactorial disease with both heritable and environmental origins. Overweight and obesity are the primary risk factors, present in 90% of persons with T2D. However, little is known of the intrinsic risk carried by individuals with moderate to severe obesity. The purpose of this study was to identify and analyze risk factors in obese individuals with and without clinical metabolic risk factors. We hypothesized that the insulin sensitivity of metabolically healthy obese individuals would be similar to their BMI matched counterparts. Methods: Eighty-seven sedentary adults underwent an inpatient stay consisting of anthropometric measurements, blood chemistries, body composition (DXA), aerobic capacity (VO2MAX), and insulin sensitivity testing (glucose clamp). Subjects were first stratified by BMI (&amp;lt;25 and &amp;gt;30). Those with a BMI &amp;gt;30 were further stratified based upon a composite metabolic health score consisting of: BMI, VO2MAX, HOMA-IR, triglycerides, and cholesterol levels. Group differences were assessed using a one-way ANOVA with multiple comparisons. Results: Individuals with obesity had elevated HDL, LDL, blood pressure, waist-to-hip ratio and body fat (ALL P&amp;lt;0.05) compared to lean controls, with no differences between metabolically healthy and unhealthy individuals. Metabolically unhealthy individuals had elevated fasting insulin (P&amp;lt;0.05) and glucose (P&amp;lt;0.05) levels compared to both lean controls and metabolically healthy obese individuals. However, both the metabolically healthy and unhealthy obese individuals had reduced insulin sensitivity (lean to obese P&amp;lt;0.01, interaction P=0.40) compared to lean controls. Conclusions: Metabolically healthy obese individuals retain the risk associated with T2D, most notable being reduced insulin sensitivity. Furthermore, we posit that safe and effective treatments for T2D, such as insulin sensitizing therapy or bariatric surgery, may be warranted in metabolically healthy obese individuals alike. Disclosure C.L. Axelrod: None. A. Hari: None. J.T. Mey: None. R.A. Beyl: None. J.P. Kirwan: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; Louisiana Clinical &amp; Translational Science Center

Increased serum resistin levels in metabolically unhealthy compared to metabolically healthy obese individuals; correlation with circulating white blood cell subpopulations

Increased serum resistin levels in metabolically unhealthy compared to metabolically healthy obese individuals; correlation with circulating white blood cell subpopulations

Тhe prevalence of metabolically healthy obesity: data from the epidemiological survey in of Novosibirsk

Background: Obesity is associated with numerous metabolic complications, such as type 2 diabetes mellitus (DM2), dyslipidemia, arterial hypertension (AH), cardiovascular diseases and some forms of cancer. Nevertheless, the literature describes a group of obese individuals who are more resistant to the development of metabolic disorders. At present, this phenomenon is known as "Metabolically healthy obesity", "metabolically healthy obesity" (MZO). Despite the presence of excess weight or obesity, a favorable metabolic profile can be observed in this cohort of patients, characterized by preserved insulin sensitivity, absence of arterial hypertension, normal lipid, hormonal profile, absence of inflammation and unchanged hepatic transaminases.&#x0D; Aims: To study the prevalence of metabolically healthy obesity (MHO) and its characteristics in men and women at the age of 4569 years in Novosibirsk.&#x0D; Materials and methods: To study covered 3197 persons from the base of the international project HAPPIE. They had a body mass index (BMI 30 kg/m). Metabolically healthy obesity was determined as obesity (BMI 30 kg/m, with 2 and fewer components of metabolic syndrome (MS) by criteria NCEP ATP III, 2001. Statistical analisys SPSS-13.&#x0D; Results: The prevalence of metabolic healthy obesity (MHO) was 42% (38% for men and 43% for women). The examined people with MHO have reliably more favorable average level of TG, HDL-cholesterol, indicators of blood glucose, systolic arterial pressure and diastolic arterial pressure and less waist circumference. In the groups withMHO and MS abdominal obesity is common in men at 95 and 71%, in women at 99 and 90%; hyperTG in men at 74 and 9%, in women at 72 and 5,5%; lower level HDL-cholesterol in 16 and 1% for men, and in 44,5% and 3% for women; AP in 96 and 77% and 94 and 71% in men and women respectively, the frequency fasting of hyperglycaemia 77 and 21% in men and 60 and 5% in women was markedly different. According to the data obtained by us, the frequency in the sample is high and amounted to 42%. In the subgroup the most commonly found is the MHO phenotype 53%, than in the men -38%, р 0,001&#x0D; Conclusions: According to our data, the frequency of metabolic healthy obesity in the sample is high and amounted to 42%. In the female subgroup, a metabolically healthy phenotype is more common 43% than in the male 38%, p 0.001. Metabolically healthy obese individuals are characterized by a significantly lower incidence of fasting hyperglycaemia and dyslipidemia.

Obesity and risk of hearing loss: A prospective cohort study

The existing yet limited prospective studies reported conflicting results about obesity and hearing loss. We investigated the prospective association between obesity and hearing loss in a large-scale Japanese working population, as well as the association between metabolic phenotype and hearing loss. The study included 48,549 employees aged 20-64 years and free of hearing loss at baseline. Pure-tone audiometric testing was performed annually to identify hearing loss at 1 and 4kHz. Cox proportional hazards regression was used to investigate the risk of hearing loss associated with body mass index (BMI) and metabolic phenotype (based on a BMI of ≥25.0/<25.0kg/m2 and presence/absence of ≥2 components of metabolic syndrome, except waist circumference). Baseline and updated information were obtained from annual health checkups. With a median follow-up of 7 years, 1595 and 3625 individuals developed unilateral hearing loss at 1 and 4kHz, respectively. The adjusted hazard ratios (HR) for hearing loss at 1kHz were 1.21 (1.08, 1.36) and 1.66 (1.33, 2.08) for those with BMI 25.0-29.9kg/m2 and BMI ≥30.0kg/m2, respectively, compared to individuals with BMI <25.0kg/m2. For hearing loss at 4kHz, the corresponding HRs were 1.14 (1.05, 1.23) and 1.29 (1.09, 1.52). Compared with metabolically healthy non-obese individuals, the adjusted HRs for hearing loss at 1kHz were 1.19 (1.03, 1.39), 1.27 (1.01, 1.61), and 1.48 (1.25, 1.76) for unhealthy non-obese, healthy obese, and unhealthy obese individuals, respectively. For hearing loss at 4kHz, the corresponding HRs were 1.13 (1.04, 1.25), 1.21 (1.04, 1.41), and 1.26 (1.12, 1.41). Overweight and obesity are associated with an increased risk of hearing loss, and metabolically unhealthy obesity may confer additional risk.

Abstract P069: Longitudinal Associations Between Metabolic Status, Insulin Clearance, and Insulin Sensitivity: The Prospective Metabolism and Islet Cell Evaluation (PROMISE) Cohort

Metabolically healthy obese individuals (MHO) are those with obesity but normal metabolic profiles. The relationship of MHO to type 2 diabetes mellitus (T2DM) risk is unclear. Limited data are available on metabolic status and declining insulin clearance (IC) and insulin sensitivity (IS), which are well-documented features in the pathogenesis of T2DM. Objective: To assess longitudinal changes in IC and IS among metabolically healthy and unhealthy obese and non-obese participants. Hypothesis: Longitudinal declines in IC and IS will be greater among participants classified as metabolically unhealthy and/or obese compared to metabolically healthy non-obese (MHN). Methods: Adults ≥30 years old at-risk for T2DM in PROMISE had three assessments over 6 years (n=558). Obesity was classified as BMI ≥30 kg/m 2 . Baseline metabolic parameters, including blood pressure, TAG, HDL, fasting glucose, waist circumference, and medication use, were used to determine metabolic status. Metabolically healthy status was defined as the presence of &lt;3 metabolic abnormalities. Values from oral glucose tolerance tests at each visit were used to calculate Matsuda insulin sensitivity index (ISI), and the ratios of fasting C-peptide-to-insulin (IC FASTING ) and areas-under-the-curve of C-peptide-to-insulin (IC AUC ). Generalized estimating equations (GEE) evaluated the association of baseline metabolic status with longitudinal changes in IC and IS, adjusting for covariates. Results: The multivariate GEE model showed that MHO and MUO had greater declines in IC and IS over time compared to MHN ( Figure , both p&lt;0.01). Metabolically unhealthy non-obese (MUN) had a longitudinal decline in IC FASTING but not IC AUC compared to MHN, and a more modest relative decline in IS. Conclusions: Compared to MHN, presence of a metabolically unhealthy and/or obese phenotype negatively impacted IC and IS over time. The more pronounced declines in IC in MUO and MHO may reflect a compensatory response to the poorer IS in these groups.

Abstract P335: Greater Frequency of Olive Oil Consumption is Associated with Lower Platelet Activation in Obesity

Healthy lifestyle behaviors, including maintenance of normal weight, are associated with lower risk of atherothrombotic events. In the general population, consumption of olive oil and a Mediterranean diet are associated with reduced risk of cardiovascular disease (CVD). However, less is known about how this affects individuals with obesity. We investigated whether olive oil intake is associated with reduced platelet activation in a cohort of obese, non-smoking, non-diabetic subjects without known CVD. As part of a larger prospective study of platelet function in obesity, we assessed platelet activation (surface P-selectin and PAC1 MFI) with and without agonist (0.025U thrombin, 0.1uM ADP, 0.4uM epinephrine) exposure via flow cytometry. Food frequency surveys were used to estimate diet composition. Subjects were stratified by food intake frequency and platelet activation was compared using ANOVA, with post-hoc independent samples t-testing. Among 63 subjects, the mean age was 32.2 ± 8.0 years and BMI 44.1 ± 8.5 kg/m 2 . Olive oil intake frequency was stratified into 3 groups: ≤ 1 time/wk, n=21; 1 - 3 times/wk, n=18; ≥ 4 times/wk, n=24. The groups did not differ by age, weight, BMI, waist and hip circumferences, platelet count or mean platelet volume. Subjects with more frequent olive oil intake showed lower platelet activation to agonists than those consuming olive oil ≤ 1 time/wk (Figure). Non-agonized platelet activity did not differ significantly by olive oil intake frequency. Notably, we did not observe associations between platelet activity and consumption of red meat, eggs, butter, or margarine. In metabolically healthy obese individuals, more frequent olive oil intake is associated with suppressed platelet activation. We hypothesize that phenolic compounds in olive oil may alter platelet membrane phospholipid content, making platelets less susceptible to activation. For obese individuals, olive oil intake may lower risk of cardiovascular events.

Hepatic transcriptome signatures in patients with varying degrees of nonalcoholic fatty liver disease compared with healthy normal-weight individuals.

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of conditions ranging from simple steatosis (NAFL), over nonalcoholic steatohepatitis (NASH) with or without fibrosis, to cirrhosis with end-stage disease. The hepatic molecular events underlying the development of NAFLD and transition to NASH are poorly understood. The present study aimed to determine hepatic transcriptome dynamics in patients with NAFL or NASH compared with healthy normal-weight and obese individuals. RNA sequencing and quantitative histomorphometry of liver fat, inflammation and fibrosis were performed on liver biopsies obtained from healthy normal-weight ( n = 14) and obese ( n = 12) individuals, NAFL ( n = 15) and NASH ( n = 16) patients. Normal-weight and obese subjects showed normal liver histology and comparable gene expression profiles. Liver transcriptome signatures were largely overlapping in NAFL and NASH patients, however, clearly separated from healthy normal-weight and obese controls. Most marked pathway perturbations identified in both NAFL and NASH were associated with markers of lipid metabolism, immunomodulation, extracellular matrix remodeling, and cell cycle control. Interestingly, NASH patients with positive Sonic hedgehog hepatocyte staining showed distinct transcriptome and histomorphometric changes compared with NAFL. In conclusion, application of immunohistochemical markers of hepatocyte injury may serve as a more objective tool for distinguishing NASH from NAFL, facilitating improved resolution of hepatic molecular changes associated with progression of NAFLD. NEW & NOTEWORTHY Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. NAFLD is associated with the metabolic syndrome and can progress to the more serious form, nonalcoholic steatohepatitis (NASH), and ultimately lead to irreversible liver damage. Using gold standard molecular and histological techniques, this study demonstrates that the currently used diagnostic tools are problematic for differentiating mild NAFLD from NASH and emphasizes the marked need for developing improved histological markers of NAFLD progression.

Impact of Self-Rated Health on Progression to a Metabolically Unhealthy Phenotype in Metabolically Healthy Obese and Non-Obese Individuals.

We examined the association between self-rated health (SRH), a subjective measure of an individual’s health status, and the incidence of metabolic abnormalities, as well as the effect of obesity on this association in metabolically healthy individuals. The cohort study included 85,377 metabolically healthy men and women who were followed annually or biennially for a median of 3.0 years (interquartile range, 1.9–4.1 years). A parametric proportional hazard model was used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between SRH and the incidence of metabolic abnormalities. During 258,689.03 person-years, 40,858 participants developed metabolic abnormalities. Poorer SRH was significantly associated with increased risk of developing any metabolic abnormality including hypertriglyceridemia, high homeostasis model assessment of insulin resistance (HOMA-IR), and fatty liver in a dose-dependent manner (p for trend <0.05). The association between SRH and progression to metabolically unhealthy status was much stronger in individuals with obesity than those without, especially in relation to any metabolic abnormality, fatty liver, and high C-reactive protein (all p for interaction by obesity <0.05). The multivariable-adjusted HR (95% CI) for any metabolic abnormality comparing the “poor or very poor” vs. the “very good” self-rated health category was 0.97 (0.90–1.05) among non-obese subjects, whereas the corresponding HR (95% CI) among obese subjects was 1.25 (1.02–1.52). Low SRH, as assessed by a single question, was independently associated with increased risk of progression to metabolically unhealthy status in metabolically healthy individuals, especially metabolically healthy individuals with obesity. SRH may help identify individuals at high risk for progression to metabolically unhealthy status.

Risk of type 2 diabetes in metabolically healthy people in different categories of body mass index: an updated network meta-analysis of prospective cohort studies.

Introduction: Risk of diabetes mellitus type 2 (T2DM) is variable between individuals due to different metabolic phenotypes. In present network meta-analysis, we aimed to evaluate the risk of T2DM related with current definitions of metabolic health in different body mass index (BMI) categories. Methods: Relevant articles were collected by systematically searching PubMed and Scopus databases up to 20 March 2018 and for analyses we used a random-effects model. Nineteen prospective cohort studies were included in the analyses and metabolically healthy normal weight (MHNW) was considered as the reference group in direct comparison for calculating indirect comparisons in difference type of BMI categories. Results: Total of 199403 participants and 10388 cases from 19 cohort studies, were included in our network meta-analysis. Metabolically unhealthy obesity (MUHO) group poses highest risk for T2DM development with 10 times higher risk when is compared with MHNW (10.46 95% CI; 8.30, 13.18) and after that Metabolically unhealthy overweight (MUOW) individuals were at highest risk of T2DM with 7 times higher risk comparing with MHNW (7.25, 95% CI; 5.49, 9.57). Metabolically healthy overweight and obese (MHOW/MHO) individuals have (1.77, 95% CI; 1.33, 2.35) and (3.00, 95% CI; 2.33, 3.85) risk ratio for T2DM development in comparison with MHNW respectively. Conclusion: In conclusion we found that being classified as overweight and obese increased the risk of T2DM in comparison with normal weight. In addition, metabolically unhealthy (MUH) individuals are at higher risk of T2DM in all categories of BMI compared with metabolically healthy individuals.

Effect of obesity on cardiac function in healthy individuals without any other cardiac comorbidities - A study based on echocardiography

Background: Obesity constitutes a major health issue in the modern world because of its association with morbidity, mortality, and cardiovascular diseases (CVD). The excess in body fat determines a rise in each preload and afterload leading to a hyperdynamic circulation, chronic volume overload and increase in peripheral resistance. Impairment of cardiac function has been reported to correlate with body mass index (BMI) and duration of obesity, with most studies reporting abnormal diastolic function. Aims and Objectives: The aim of the study was to assess the effect of obesity on the left and right ventricular (RV) function by conventional two-dimensional (2D) echocardiography in non-hypertensive, nondiabetic healthy obese individuals. Materials and Methods: A total of 60 healthy subjects aged between 18 and 30 years, without any comorbid conditions for CVD such as hypertension, diabetes mellitus, and chest pain were enrolled in the study. Demographic data including height, weight, and blood pressure were collected from all the subjects through a detailed medical history and physical examination. 2D echocardiography was performed using Philips iE33 (Andover, MA, USA) echo machine by a trained sonographer who is blinded to the study. Results: Obesity has an impact on left ventricular (LV) function as there is a significant increase in Tei index for LV (P < 0.001) and LVEDV (P = 0.046). Obesity has no effect on RV function as there is no change in tricuspid annular plane systolic excursion (P = 0.628) and Tei index for RV (P = 0.682). Obesity has no effect on LV ejection fraction (P = 1.00). LV mass left atrial (LA) diameter, septal wall diameter (IVSd), and posterior wall diameter are significantly increased with an increased BMI. Conclusion: The present study concluded that obese individuals with BMI ≥27.5 kg/m2 have increased LV wall thickness and LV mass, significantly higher risk of LV diastolic dysfunction. Although LA enlargement is associated with diastolic dysfunction which is an evidence of subclinical LV systolic dysfunction, we found no change in LVEF in all the groups which indicates that obesity does not have any effect on LV systolic function.

Body Mass Index as a Determinant of Systemic Exposure to Gallotannin Metabolites during 6-Week Consumption of Mango (Mangifera indica L.) and Modulation of Intestinal Microbiota in Lean and Obese Individuals.

This human clinical pilot trial investigated pharmacokinetics of gallotannin-metabolites and modulation of intestinal microbiota in healthy lean and obese individuals after 6 weeks of daily mango consumption. Participants are divided into three groups: Lean Mango (LM: n = 12; BMI = 22.9 kg m-2 ), Obese Mango (OM: n = 9; BMI = 34.6 kg m-2 ), and Lean Control (LC: n = 11; BMI = 22.1 kg m-2 ). LM and OM consumed 400 g of mango per day for 6 weeks. LC consumed mango only on Days 0 and 42. After 6 weeks, LM experienced increased systemic exposure (AUC0-8h ) to gallotannin-metabolites, 1.4-fold (p = 0.043). The greatest increase is 4-O-methyl-gallic acid, 3.3-fold (p = 0.0026). Cumulative urinary excretion of gallotannin-metabolites significantly increased in LM and OM, but not LC. For OM, qPCR data show increased levels of tannase-producing Lactococcus lactis and decreased levels of Clostridium leptum and Bacteroides thetaiotaomicron, bacteria associated with obesity. LM experienced an increased trend of fecal levels of butyric (1.3-fold; p = 0.09) and valeric acids (1.5-fold; p = 0.056). Plasma endotoxins showed a decreased trend in LM and OM. Continuous mango intake significantly increased systemic exposure to gallotannin- metabolites and induced an increased trend for fecal short-chain fatty acids in lean but not obese individuals. This pharmacokinetic discrepancy may result in BMI-associated reduced gallotannin-derived health benefits.