Healthy Non-obese Individuals Research Articles

Associations Between Metabolic Obesity Phenotypes and Pathological Characteristics of Papillary Thyroid Carcinoma

ObjectiveThe association between obesity, metabolic dysregulation, and the aggressive pathological traits of papillary thyroid carcinoma (PTC) continues to be a contentious issue. To date, no investigations have examined the impact of metabolic status on the malignant pathological features of PTC in relation to obesity. MethodsThis research involved 855 adult patients with PTC from Shandong Provincial Hospital, classified into 4 groups based on metabolic and obesity status: metabolically healthy nonobese, metabolically unhealthy nonobese (MUNO), metabolically healthy obese, and metabolically unhealthy obese. We employed logistic regression to investigate the relationship between these metabolic obesity phenotypes and PTC's pathological characteristics. Mediation analysis was also performed to determine metabolic abnormalities' mediating role in the nexus between obesity and these characteristics. ResultsRelative to metabolically healthy nonobese individuals, the metabolically unhealthy obese group was significantly associated with an elevated risk of larger tumor sizes and a greater number of tumor foci in PTC. Mediation analysis indicated that obesity directly influences tumor size, whereas its effect on tumor multifocality is mediated through metabolic dysfunctions. Specifically, high-density lipoprotein cholesterol levels were notably associated with tumor multifocality within obese subjects, serving as a mediator in obesity's impact on this trait. ConclusionThe concurrent presence of obesity and metabolic dysregulation is often connected to more aggressive pathological features in PTC. The mediation analysis suggests obesity directly affects tumor size and indirectly influences tumor multifocality via low high-density lipoprotein cholesterol levels.

Abnormal adiposity indices are associated with an increased risk of diabetes in a non-obese Asian population

ObjectivesThe aim of this study was to evaluate the association between adiposity indices and the risk of incident diabetes and to compare their predictive ability in non-obese healthy individuals. Study designPopulation-based cohort study. MethodsData were taken from the NAGALA research study, which enrolled Japanese adults aged 18–79 years. Cox regression was used to evaluate the association between adiposity indices (including waist circumference [WC], waist-to-height ratio [WHtR], lipid accumulation product index [LAP], body roundness index [BRI], visceral adiposity index [VAI] and Chinese visceral adiposity index [CVAI]) and diabetes risk. The performance of the indices for predicting diabetes was explored using area under the receiver operating characteristic curve (AUC). A Chinese community–based population was used for validation. ResultsA total of 12,940 healthy Japanese individuals with normal body mass index and glycaemic levels were included and were followed up for a median of 6 years. Multivariable Cox models revealed a positive and significant association between all indices and incident diabetes, with the hazard ratios for the highest quartile of the indices ranging from 1.89 to 2.90 (all P-values < 0.01). A non-linear association between WC, BRI and VAI and a linear association between WHtR, LAP and CVAI and diabetes risk were observed. CVAI, VAI and LAP had comparable ability in predicting diabetes, with the highest AUC being 0.733 for CVAI. Data from 10,830 Chinese individuals confirmed these results. ConclusionsAdiposity indices are associated with incident diabetes in healthy non-obese individuals. Participants in the highest quartile of WC, WHtR, LAP, BRI, VAI and CVAI had an increased risk of developing diabetes.

Between-sexes differences in lumbopelvic muscle mechanical properties of non-climacteric adults: a cross-sectional design

The lumbopelvic muscle mechanical properties (MMPs) are clinically relevant, but their dependence on sex remains unknown. Therefore, this study aimed to identify if lumbopelvic MMPs depend on the sex in a young adult population. Thirty-five healthy nulliparous women and 35 healthy men were analyzed (age range: 18–50). Lumbopelvic MMPs, that is, tone, stiffness, elasticity, relaxation and creep, assessed with MyotonPRO®, and pelvic floor (PF) health questionnaires were compared between-sexes. Intra-group correlations between sociodemographic and clinical data, and MMPs were also determined. The MMPs of PF were different between healthy non-climacteric adults of both sexes, with women showing higher values of tone and stiffness and lower values of elasticity and viscoelastic properties than men (in all cases, p < 0.03). At lumbar level, tone and stiffness were higher for men at both sides (in all cases, p < 0.04), and relaxation was lower at left side (p = 0.02). The MMPs showed few correlations with sociodemographic data within women. However, within males, there were positive correlations for PF stiffness and viscoelastic parameters with age, BMI and function (0.334 < r < 0.591) and, at lumbar level, negative correlations for tone and stiffness ( − 0.385 < r < −0.590) and positive correlations for viscoelastic properties (0.564 < r < 0.719), with BMI. This indicated that between-sexes differences of lumbopelvic MMPs depend on the specific location of assessment in healthy non-obese young individuals. Women show higher tone and stiffness and lower elasticity and viscoelasticity than men, at PF level.

Effects of smoking on the cardiopulmonary modulation during physical exercise in middle-aged non-obese healthy individuals

Objective:&#x0D; The aim of this study was to evaluate the overall effects of smoking and its duration on various cardiopulmonary modulation mechanisms during physical exercise in middle-aged non-obese healthy individuals.&#x0D; Materials and Methods:&#x0D; Two hundred forty-three (142 smokers and 101 non-smokers), middle-aged, non-obese, healthy individuals were evaluated in this cross-sectional study. Parameters of pulmonary function including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and FEV1/FVC ratio were evaluated using a spirometer and systolic pulmonary artery pressure (sPAP) were measured by echocardiography on rest and during various levels of exercise. A treadmill exercise test was used to assess heart rate recovery index (HRRI), the chronotropic index (CI) and the maximum rate of oxygen consumption during exercise (VO2max). &#x0D; Results:&#x0D; Resting sPAP values were higher and FEV1, FVC and FEV1/FVC values were lower among smokers. As compared to resting values; FEV1 and FEV1/FVC ratio in smokers decreased significantly at peak exercise level (2.66±0.54 vs 2.35±0.49, p

Metformin Affects Plasma Levels of Soluble Leptin Receptors in Type 2 Diabetes Mellitus and Metabolic Syndrome Patients

Background: Obesity and insulin resistance elevate plasma leptin, while it lowers plasma levels of soluble leptin receptors (sOB-R).Objectives: To measure the levels of sOB-R in patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) and compare it to healthy controls. The study also aimed to investigate the influence of metformin on the levels of sOB-R in patients with T2DM and MetS. Materials and Methods: A cross-sectional study was conducted on 66 participants (33 patients and 33 controls). Patients were divided into two groups; Group I included 17 newly diagnosed T2DM patients, and Group II included 16 patients with MetS. Patients were studied before and 3 months after treatment with 850 mg metformin treatment. Group III included 33 non-obese healthy individuals as a control group. Measurements such as height, weight, waist circumference, hip circumference, blood pressure examination, and biochemical tests including fasting blood sugar, HbA1c, total cholesterol (Ch), triglyceride, high-density lipoprotein (HDL), insulin level, plasma sOB-R levels were performed. Ch/HDL ratio, non-HDL cholesterol, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Waist Hip Ratio (WHR), and Body Mass Index (BMI) were calculated.Results: No statistically significant difference was found among the groups regarding sOB-R levels initially, but after metformin treatment, T2DM patients showed a significantly higher level (10.19 ng/ml). There was a significant increase in the levels of sOB-R after metformin treatment, as it increased from 7.82 ng/ml to 10.19 ng/ml in T2DM, and from 6.92 ng/ml to 7.82 ng/ml in MetS patients. Conclusion: Metformin significantly increases the plasma levels of sOB-R in T2DM patients but only slightly increases these levels in MetS patients.

Well-controlled versus poorly controlled diabetes in patients with obesity: differences in MRI-evaluated pancreatic fat content.

Patients with obesity and poorly controlled type 2 diabetes (T2D) are at high risk of diabetic complications. This study aimed to determine the associations of visceral adipose tissue (VAT), hepatic proton-density fat fraction (PDFF), and pancreatic PDFF with poor glycemic control in patients with obesity and T2D and to evaluate the metabolic effect of bariatric surgery in patients with obesity and poorly controlled diabetes. In this retrospective cross-sectional study, from July 2019 to March 2021, 151 consecutive obese patients with new-onset T2D (n=28), well-controlled T2D (n=17), poorly controlled T2D (n=32), prediabetes (n=20), or normal glucose tolerance (NGT; n=54) were included. A total of 18 patients with poorly controlled T2D were evaluated before and 12 months after bariatric surgery, and 18 non-obese healthy individuals served as controls. VAT, hepatic PDFF, and pancreatic PDFF were quantified by magnetic resonance imaging (MRI) using a chemical shift-encoded sequence [iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation (IDEAL-IQ)]. Univariate analysis and multivariate regression analysis were performed. There were significant differences in VAT, hepatic PDFF, and all pancreatic PDFF between the new-onset T2D, prediabetes, and NGT groups (all P<0.05). Pancreatic tail PDFF was significantly higher in the poorly controlled T2D group than in the well-controlled T2D group (P=0.001). In the multivariate analysis, only pancreatic tail PDFF was significantly associated with increased odds of poor glycemic control [odds ratio (OR) =2.09; 95% confidence interval (CI): 1.11-3.94; P=0.022]. The glycated hemoglobin (HbA1c), hepatic PDFF, and pancreatic PDFF significantly decreased (all P<0.01) after bariatric surgery, and the values were statistically similar to those observed in the non-obese healthy controls. Increased fat in the pancreatic tail is strongly associated with poor glycemic control in patients with obesity and T2D. Bariatric surgery is an effective therapy for poorly controlled diabetes and obesity, which improves glycemic control and decreases ectopic fat deposits.

The Metabolic Switch of Physical Activity in Non-Obese Insulin Resistant Individuals.

Healthy non-obese insulin resistant (IR) individuals are at higher risk of metabolic syndrome. The metabolic signature of the increased risk was previously determined. Physical activity can lower the risk of insulin resistance, but the underlying metabolic pathways remain to be determined. In this study, the common and unique metabolic signatures of insulin sensitive (IS) and IR individuals in active and sedentary individuals were determined. Data from 305 young, aged 20-30, non-obese participants from Qatar biobank, were analyzed. The homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires were utilized to classify participants into four groups: Active Insulin Sensitive (ISA, n = 30), Active Insulin Resistant (IRA, n = 20), Sedentary Insulin Sensitive (ISS, n = 21) and Sedentary Insulin Resistant (SIR, n = 23). Differences in the levels of 1000 metabolites between insulin sensitive and insulin resistant individuals in both active and sedentary groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. The study indicated significant differences in fatty acids between individuals with insulin sensitivity and insulin resistance who engaged in physical activity, including monohydroxy, dicarboxylate, medium and long chain, mono and polyunsaturated fatty acids. On the other hand, the sedentary group showed changes in carbohydrates, specifically glucose and pyruvate. Both groups exhibited alterations in 1-carboxyethylphenylalanine. The study revealed different metabolic signature in insulin resistant individuals depending on their physical activity status. Specifically, the active group showed changes in lipid metabolism, while the sedentary group showed alterations in glucose metabolism. These metabolic discrepancies demonstrate the beneficial impact of moderate physical activity on high risk insulin resistant healthy non-obese individuals by flipping their metabolic pathways from glucose based to fat based, ultimately leading to improved health outcomes. The results of this study carry significant implications for the prevention and treatment of metabolic syndrome in non-obese individuals.

Cohort profile update: The Cork and Kerry Diabetes and Heart Disease Study.

Background: The Cork and Kerry Diabetes and Heart Disease Study was established to investigate the prevalence of diabetes and cardiovascular disease among middle-aged adults in Ireland. The Mitchelstown cohort was recruited from a single large primary care centre between 2010-2011. A rescreen of this cohort was conducted in 2015. Methods: Data were collected on cardiovascular health and associated risk factors. In addition, the rescreen incorporated new measures which included information on cognition and frailty, medication adherence, dietary factors and the collection of stool samples with RNA sequencing of the gut microbiome. Results: Of 2047 participants in the original cohort, 237 (11.6%) were deceased, too ill to participate or were lost to follow-up. Of the remaining 1810 baseline study participants, 1378 men and women aged 51-77 years agreed to take part in the rescreen (response rate of 76.1%). The prevalence of hypertension was high, ranging from 50% to 64% depending on the measurement method. An investigation of the association of gut microbiota with metabolic syndrome and obesity indicated greater microbiome diversity in metabolically healthy non-obese individuals relative to their unhealthy counterparts. Analysis of prescribing data over time demonstrated a high prevalence of potentially inappropriate prescribing among older-aged people in primary care which increased as they progressed to more advanced old age. Conclusions: The rescreen has provided new insights into cardiovascular health. In addition, this study is embedded in a single primary care centre, enabling passive follow-up of study participants through electronic health records. All data collected at baseline and rescreen are maintained and stored at the School of Public Health, University College Cork and specific proposals for future collaborations are welcome.

Alterations in the gut microbiota composition in the obesity phenotype of heart failure with preserved ejection fraction

Abstract Introduction Obesity is one of the most common phenotypes of heart failure with preserved ejection fraction (HFpEF). A growing body of evidence indicates that obesity is characterized by compositional alterations in the intestinal microbiota and its metabolites, collectively referred as dysbiosis. Purpose We sought to investigate whether the obese phenotype of HFpEF is mediated by further alterations in the microbiota and whether gut dysbiosis fuels metabolic inflammation leading to progression of HFpEF. Methods HFpEF was induced in C57/black mice by high-fat diet and inhibition of NO synthesis (a “2-hit-model”) (Figure 1A). High-frequency echocardiography was performed to assess diastolic function. Blood pressure (BP) was measured using CODA non-invasive tail-cuff system. For human studies, patients with obese HFpEF as well as obese and non-obese healthy individuals were prospectively recruited. Gut microbial DNA was subjected to 16S ribosomal RNA gene sequencing, and the differences in abundance and composition of bacteria were defined both in humans and mice. Results In mice, the 2-hit model demonstrated significantly increased BP and impaired diastolic function in the obese HFpEF group (Figure 1B). Microbiome analysis showed significant differences in the gut microbial diversity and composition in the obese HFpEF compared to the non-HFpEF obese and chow-fed mice (Figure 1C). Similarly, human microbiome sequencing showed significant gut bacterial alterations in the diversity and composition of bacteria with more profound dysbiosis observed in the obese HFpEF patients compared to the obese and lean healthy individuals (Figure 1D). Conclusions We provide evidence in humans as well as in a murine animal model that the obese HFpEF phenotype is associated with more pronounced gut dysbiosis compared to the non-HFpEF obesity state. Further research will elucidate the causative link between gut dysbiosis and HFpEF manifestation and the mechanistic insights into the implication of gut microbiota in HFpEF progression. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Israel science foundation

Serum Level of Inhibin B and Kisspeptin, as well as Their Correlation with Biochemical Factors in Obese Adult Patients.

Obesity is one of the most important global health problems causing serious health risks and early death in human. It is also associated with disturbance of homeostasis of hormones and immunological biochemical factors inside the human body. This study aimed to evaluate the serum level of inhibin B and kisspeptin among Iraqi obese adult people and other biochemical parameters correlated with obesity. Inhibin B and levels of kisspeptin were evaluated in the samples of serum from 40 Iraqi obese adult patients and 30 healthy non-obese individuals. A significant decrease (P<0.0001) was observed in the kisspeptin level in both males and females, compared to the control group. Moreover, inhibin B decreased significantly in obese females only (P<0.001), while there was no differences between males and the control group in this regard. Finally, body mass index, serum glutamic pyruvic transaminase (SGPT), and leptin showed negative correlation with kisspeptin (0.01, 0.5, and 0.01), respectively. However, a positive association was observed with the level of Ca in the serum. On the other hand, inhibin B confirmed a positive correlation with SGPT. The present study revealed a significant increase in inhibin B and kisspeptin, with SGPT and Ca in the serum of obese patients, which could lead to complications and health problems among these patients.

Clinico-investigative study of facial acanthosis nigricans

Background:Facial acanthosis nigricans (FAN) is an underrecognized and underdiagnosed entity. The typical presentation of acanthosis nigricans (AN) seen elsewhere on the body like axillae and groins is not seen on the face, making it mimic other pigmentary disorders. Moreover, FAN is seldom not accompanied with AN on the classical sites making the diagnosis challenging. The aims of this study were to determine clinical, dermoscopic, and histopathological features of FAN and to estimate the prevalence of obesity and insulin resistance (IR) in FAN.Methods:Forty cases of FAN and forty healthy nonobese individuals with comparable ages and gender were included in the study. Body mass index, waist circumference, hip circumference, waist to hip ratio, and serum fasting lipid levels were used to evaluate obesity, whereas serum fasting insulin and Homeostatic Model of Assessment of Insulin Resistance (HOMA-IR) were used to evaluate IR. Dermoscopy was performed in all cases. Histopathological features of the skin biopsies were reviewed.Results:Out of the 40 cases, 24 were male and 16 were female. The patterns of facial pigmentation in addition to the classic pattern were a hyperpigmented band over forehead (55%), periorbital darkening (25%), perioral (10%), and generalized darkening (10%). Dermoscopy in all cases revealed linear crista cutis, sulcus cutis, and hyperpigmented dots in crista cutis. Biopsy of 20 cases showed mild hyperkeratosis, acanthosis, papillomatosis, and increase in basal melanin. Clinico-dermoscopic-histological correlation showed that milder (light brown) variants of FAN had follicular plugging and subtle sulci pattern with irregular brown globules and perifollicular pigmentation on dermoscopy and mild hyperkeratosis and hypermelanization of the basal layer with minimal acanthosis and papillomatosis on histopathology. On the other hand, chronic variants (dark brown and black) showed prominent sulci, larger brown globules, and perifollicular hyperpigmentation on dermoscopy and moderate hyperkeratosis and hypermelanization of the basal layer with moderate to severe acanthosis and papillomatosis on histopathology. Fasting blood glucose, insulin, HOMA-IR, fasting serum triglyceride, and total cholesterol were statistically significantly high in cases in comparison with controls (P-value <0.05).Conclusions:Varied clinical presentations of FAN were observed. Dermoscopy and histopathology provide a good aid. FAN may be considered as a cutaneous marker of obesity and IR. Thus, FAN should be suspected in patients presenting with facial melanosis who are obese and have AN over other sites, although FAN can also present de novo.

Cardiovascular events in metabolically healthy obese. A nationwide cohort study

Abstract Background Obesity is a risk factor for cardiovascular disease (CVD) and has been increasing globally over the past 40 years in many countries worldwide. Metabolic abnormalities such as hypertension, dyslipidemia and diabetes mellitus are commonly associated and may mediate some of the deleterious effects of obesity. A subset of obese individuals without obesity-related metabolic abnormalities may be classified as being “metabolically healthy obese” (MHO). We aimed to evaluate the associations among MHO individuals and different types of incident cardiovascular events in a contemporary population at a nationwide level. Methods From the national hospitalization discharge database, all patients discharged from French hospitals in 2013 with at least 5 years or follow-up and without a history of major adverse cardiovascular event (myocardial infarction, heart failure [HF], ischemic stroke or cardiovascular death, MACE-HF) or underweight/ malnutrition were identified. They were categorized by phenotypes defined by obesity and 3 metabolic abnormalities (diabetes mellitus, hypertension, and hyperlipidemia). In total, 2,953,816 individuals were included in the analysis, among whom 272,838 (9.5%) were obese. We evaluated incidence rates and hazard ratios for MACE-HF, cardiovascular death, myocardial infarction, ischemic stroke, new-onset HF and new-onset atrial fibrillation (AF). Adjustments were made on age, sex and smoking status at baseline. Results During a mean follow-up of 4.9 years, obese individuals with no metabolic abnormalities had a higher risk of MACE-HF (multivariate-adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI]: 1.19–1.24), new-onset HF (HR 1.34, 95% CI 1.31–1.37), and AF (HR 1.33, 95% CI 1.30–1.37) compared with non-obese individuals with 0 metabolic abnormalities. By contrast, risks were not higher for myocardial infarction (HR 0.92, 95% CI 0.87–0.98), ischemic stroke (HR 0.93, 95% CI 0.88–0.98) and cardiovascular death (HR 0.99, 95% CI 0.93–1.04). In the models fully adjusted on all baseline characteristics, obesity was independently associated with a higher risk of MACE-HF events (HR 1.13, 95% CI 1.12–1.14), of new-onset HF (HR 1.19, 95% CI 1.18–1.20) and new-onset AF (HR 1.29, 95% CI 1.28–1.31). This was not the case for the association of obesity with cardiovascular death (HR 0.96, 95% CI 0.94–0.98), myocardial infarction (HR 0.93, 95% CI 0.91–0.95) and ischemic stroke (HR 0.93, 95% CI 0.91–0.96). Conclusions Metabolically healthy obese individuals do not have a higher risk of myocardial infarction, ischemic stroke or cardiovascular death than metabolically healthy non-obese individuals. By contrast they have a higher risk of new-onset HF and new onset AF. Even individuals who are non-obese can have metabolic abnormalities and be at high risk of cardiovascular disease events. Our observations suggest that specific studies investigating different aggressive preventive measures in specific subgroups of patients are warranted. Funding Acknowledgement Type of funding sources: None.

Abstract P023: Leukocyte Count, Adiposity And Incident Diabetes In A Biracial Cohort

Background: Diabetes is one the costliest diseases in the U.S, and excess inflammation associates with greater diabetes risk. Greater adiposity is associated with higher leukocyte count, but the interrelations of body size phenotype, leukocytes, and incident diabetes is unknown. Hypothesis: Body size phenotype and incident diabetes can be further understood using leukocyte count in Black and White people. Methods: The study included 8075 Black and White participants without diabetes at baseline (2003-2007) in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Body size phenotypes included metabolically healthy non-obese, metabolically healthy obese, metabolically unhealthy non-obese, and metabolically unhealthy obese. The interaction of leukocyte count with body size phenotype was assessed. As an exploratory analysis, data were further stratified by race. Results: The interaction of leukocyte count with body size phenotype was significant (p=0.02). In metabolically healthy individuals with or without obesity, the risk of diabetes increased across leukocyte quartiles. In healthy non-obese individuals, the risk of diabetes was 3 times higher in the top compared to the bottom quartile of leukocyte count and 4.5 times higher in unhealthy obese individuals. In contrast, there was no association in metabolically unhealthy participants with or without obesity. Considering race differences, in metabolically healthy non-obese persons, the association was 4 times higher for Black individuals and 2 times higher among White individuals. In the healthy obese group, these associations was larger in White than Black people. Conclusions: Higher leukocyte count is associated with the risk of diabetes in metabolically healthy individuals with or without obesity, but not among metabolically unhealthy individuals. Inflammation, as assessed by leukocyte count, does not identify added risk among those who are already classified as metabolically unhealthy.

Granzyme B Expression in Visceral Adipose Tissue Associates With Local Inflammation and Glyco-Metabolic Alterations in Obesity.

Granzyme B (GrB) is a serine protease produced by immune and non-immune cells, able to promote multiple processes, like apoptosis, inflammation, extracellular matrix remodeling and fibrosis. GrB expression in visceral adipose tissue (VAT) was associated with tissue damage, local inflammation and insulin resistance in obesity murine model, but there is no data in humans. Aim of this study was to explore the expression of GrB in VAT from obese subjects in relation to adipose tissue injury, inflammation, metabolic alterations and GrB circulating levels. For this purpose, 85 obese individuals undergoing bariatric surgery and 35 healthy subjects (as control) were recruited at Sapienza University, Rome, Italy. Study participants underwent clinical work-up and routine biochemistry. mRNA expression of GrB in VAT and of a panel of VAT inflammatory markers was analyzed by real-time PCR. Serum GrB levels were measured by Elisa Affymetrix EBIO. We observed that 80% of obese patients expressed GrB mRNA in VAT, and GrB VAT expression was associated with the presence of local inflammation and glucose homeostasis alterations. Moreover, GrB serum levels, which were higher in obese subjects compared to non-obese healthy individuals, were associated with GrB expression in VAT and glyco-metabolic impairment. Our data show, for the first time in humans, that obese subjects with “sick” fat and altered glucose tolerance exhibit GrB expression in VAT, and suggest that GrB might contribute to obesity-related VAT inflammatory remodeling and glucose homeostasis dysregulation. Moreover, increased circulating GrB levels might represent a possible peripheral marker of VAT dysfunction in metabolic diseases.

Is metabolically healthy obesity indeed healthy at the microvascular level?

Abstract Background In the current “obesity epidemic”, obese individuals without insulin resistance, lipid disorders, or hypertension, have been called “metabolically healthy” (MHO) and considered to have intermediate cardiovascular risk, between that of healthy nonobese (HNO) individuals and of metabolically unhealthy obese (MUO). Nonetheless, this is controversial, as MHO may have subclinical abnormalities, and indeed may be a transitory state in the way to the unhealthy phenotype. Purpose To evaluate systemic microvascular reactivity in MHO, MUO and HNO. Methods Ten MHO, 10 MUO and 20 HNO individuals were studied. Obesity was considered as a BMI ≥30 kg/m2. The NCEP/ATPIII criteria, excluding waist circumference, were used to define the metabolically healthy phenotype (absence of all criteria) or unhealthy phenotype (presence of any of the criteria). Laser speckle contrast imaging coupled with skin acetylcholine (Ach) iontophoresis was employed to study cutaneous microvascular reactivity (endothelial-dependent vasodilatation), as a surrogate for systemic microvascular function, and cutaneous vascular conductance [CVC in arbitrary perfusion units of microvascular flow (APU)/mean arterial pressure (mmHg)] was measured. Results Mean age was 34.8, 36.7 and 32.3 years (P=0.17, ANOVA) and BMI was 20.7, 32.2 and 33.3 kg/m2 (P&amp;lt;0.0001) for HNO, MHO and MUO, respectively. Both MHO and MUO had significantly decreased microvascular vasodilation in comparison to HNO (Figure 1). Of note, there was no significant difference between MHO and MUO regarding CVC (both similarly decreased when compared to the healthy controls). Conclusions This study underscores that MHO is not a “benign” condition, as it has adverse effects on microvascular function, similarly to those found in MUO. The study of cutaneous microvascular function may be useful to identify subclinical abnormalities in obese individuals who might deserve more intensive management. Figure 1 Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): FAPERJ - Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro - Brazil

Gut Microbiota Associations with Metabolic Health and Obesity Status in Older Adults.

Emerging evidence links the gut microbiota with several chronic diseases. However, the relationships between metabolic syndrome (MetS), obesity and the gut microbiome are inconsistent. This study aimed to investigate associations between gut microbiota composition and diversity and metabolic health status in older adults (n = 382; median age = 69.91 [± 5 years], male = 50.79%) with and without obesity. Gut microbiome composition was determined by sequencing 16S rRNA gene amplicons. Results showed that alpha diversity and richness, as indicated by the Chao1 index (p = 0.038), phylogenetic diversity (p = 0.003) and observed species (p = 0.038) were higher among the metabolically healthy non-obese (MHNO) individuals compared to their metabolically unhealthy non-obese (MUNO) counterparts. Beta diversity analysis revealed distinct differences between the MHNO and MUNO individuals on the phylogenetic distance scale (R2 = 0.007, p = 0.004). The main genera contributing to the gut composition among the non-obese individuals were Prevotella, unclassified Lachnospiraceae, and unclassified Ruminococcaceae. Prevotella, Blautia, Bacteroides, and unclassified Ruminococcaceae mainly contributed to the variation among the obese individuals. Co-occurrence network analysis displayed different modules pattern among different metabolic groups and revealed groups of microbes significantly correlated with individual metabolic health markers. These findings confirm relationships between metabolic health status and gut microbiota composition particularly, among non-obese older adults.

Hospitalization for heart failure incidence according to the transition in metabolic health and obesity status: a nationwide population-based study

BackgroundWe aimed to investigate the hazard of hospitalization for heart failure (hHF) according to the transitions in metabolic health and obesity status.MethodsThe Korean National Health Insurance Service datasets from 2002 to 2017 were used for this nationwide, longitudinal, population-based study. The hazard of hHF was analyzed according to the eight groups stratified by stability in metabolic health and transition in obesity status among initially metabolically healthy adults who underwent two cycles of health examinations in 2009–2010 and 2013–2014 (N = 7,148,763).ResultsDuring two examinations, 48.43% of the initially metabolically healthy obese (MHO) individuals and 20.94% of the initially metabolically healthy non-obese (MHNO) individuals showed changes in their metabolic health and obesity status. During a mean follow-up of 3.70 years, 3151 individuals were hospitalized for HF. When stable MHNO individuals were set as the reference, transition to metabolically unhealthy phenotype was associated with an increased hazard of hHF; the hazard ratio (HR) and 95% confidence interval (CI) in the individuals who transformed from MHO to metabolically unhealthy non-obese was 2.033 (1.579–2.616). The constant MHO group had a 17.3% increased hazard of hHF compared with the stable MHNO group [HR (95% CI) 1.173 (1.039–1.325)]. Individuals who shifted from MHO to MHNO showed a 34.3% lower hazard of hHF compared with those who maintained the MHO category [HR (95% CI) 0.657 (0.508–0.849)].ConclusionDynamic changes in metabolic health and obesity status were observed during a relatively short interval of 3–5 years. Loss of metabolic health was significantly associated with an increased hazard of hHF. Even if metabolic health was maintained, persistent obesity remained as a risk factor for hHF, and transition from MHO to MHNO had a protective effect against hHF. Therefore, the prevention and control of obesity while maintaining metabolic health would be crucial in preventing hHF.

1473-P: Evaluation of Insulin Resistance in Healthy Nonobese Asian Indians Using TyG (Triglyceride-Glucose) Index and Its Comparison with HOMA-IR

Background: Insulin resistance(IR) is a key determinant of CV Risk and is highly prevalent in Asian Indians. However, there is limited data on IR in healthy non-obese individuals. Quantification of IR in clinical practice is a challenge and HOMA IR is the commonly used method. Triglyceride-Glucose(TyG) Index, a simple method for measuring IR, is not much used in clinical practice. This study assessed the prevalence of IR using TyG index in comparison to HOMA-IR in healthy non-obese Indians. Aims and Objectives: 1. To assess the prevalence of IR using TyG index in healthy non-obese individuals 2. To assess TyG (Triglyceride-Glucose Index)Index as a measure of IR in comparison to HOMA IR. Methodology: A total of 170 healthy non-obese individuals visiting for routine health checks were recruited in the study. Relevant anthropometric and laboratory parameters were recorded. IR was calculated using TyG index and HOMA IR using following formulae: TyG = ln (Triglycerides in mg/dL x Glucose in mg/dL/2)8 IRHOMA = (I0 × G0)/405 (I0 -fasting insulin in mIU/L, G0-fasting glucose in mg/dL)1 IR was defined as HOMA-IR &amp;gt;2.8 or TyG index &amp;gt;4.65. Prevalence of IR in the study population was calculated using both and compared. Results: Mean age of study population was 43.45±15.72 years and 55% were males. Average BMI was 22.09± 2.29 Kg/m². Systolic and diastolic BP were 117.29±7.90 and 72.12±8.37 mmHg respectively. Mean fasting blood glucose was 92.79±6.92 mg/dL, mean triglycerides 107.48 ± 28.95 mg/dL and fasting serum insulin was 11.42 ± 8.53 μU/ml. Prevalence of IR defined by TyG index was 44% as compared to 34% by HOMA IR. There was a strong correlation between TyG index and HOMA IR(p=0.006). TyG index had a high negative predictive value (74%). Conclusions: Prevalence of IR in healthy Indians is high and affects more than a third of healthy non-obese individuals. TyG index appears to be a better tool for evaluation of IR in clinical practice and has a strong correlation with HOMA IR. Disclosure C. Sharma: None. M. Arora: None. D. Gupta: None. B.M. Makkar: Advisory Panel; Self; Abbott, AstraZeneca, Biocon, Boehringer Ingelheim Pharmaceuticals, Inc., Eris Lifesciences, Novartis AG, Novo Nordisk Inc., Sanofi, USV Private Limited. Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc.

Sex-specific effects of vegetarian diet on adiponectin levels and insulin sensitivity in healthy non-obese individuals.

The beneficial influence of a vegetarian diet in reducing the risk for metabolic syndrome has been demonstrated. However, adiponectin production and secretion are scarcely studied in vegetarians, despite their important role in recovering metabolic homeostasis by reducing visceral obesity, inflammation, and insulin resistance. The aim of this study was to evaluate the effect of a vegetarian diet on serum adiponectin levels and its association with the established biomarkers of insulin sensitivity and inflammation in healthy, non-obese individuals. Adiponectin, C-reactive protein, uric acid, glucose, insulin, lymphocyte and polymorphonuclear cell counts were determined in the blood of sex- and age-matched healthy vegetarian (n = 40) and omnivore (n = 36) individuals. The homeostatic model assessment (HOMA-2) calculator was used for the β-cell function (HOMA2-%B) and insulin resistance index (HOMA2-IRI) estimation. Adiponectin levels were significantly higher in female vegetarians than the respective omnivore controls (P = 0.03), whereas no dietary-associated difference was observed in men. HOMA2-%B was significantly higher in vegetarians than in omnivore controls (P = 0.04), whereas no diet-dependent differences were found in insulin, HOMA2-IRI, inflammatory, and metabolic biomarkers. Multiple regression analysis showed that adiponectin levels were significantly predicted by the type of diet only in women (P = 0.042), whereas no associations were found in men. A vegetarian diet resulted in improved β-cell function. Favorable adiponectin and insulin sensitivity responses in women reveal a distinct effect of diet-to-metabolic homeostasis, indicating an interesting pattern of sexual dimorphism regarding the beneficial metabolic effect of a vegetarian diet.

Association of metabolically healthy obesity and elevated risk of coronary artery calcification: a systematic review and meta-analysis.

BackgroundMetabolically healthy obesity (MHO) is defined as obesity with less than two parameters of metabolic abnormalities. Some studies report that MHO individuals show similar risk of cardiovascular disease (CVD) compared with metabolically healthy non-obese (MHNO) individuals, but the results are conflicting. Coronary artery calcium (CAC) reflects the extent of coronary atherosclerosis and is a useful tool to predict future risk of CVD. The objective of this meta-analysis was to investigate whether MHO is associated with elevated risk of CAC.MethodWe searched Cochrane, PubMed, and Embase up to April 19, 2019. Prospective cohort and cross-sectional studies examining the association between MHO subjects and CAC were included with MHNO as the reference. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effect models. Subgroup analysis and meta-regression were applied to define possible sources of heterogeneity. We conducted this research following a pre-established protocol registered on PROSPERO (CRD 42019135006).ResultsA total of nine studies were included in this review and six studies with 23,543 participants were eligible for the meta-analysis. Compared with MHNO subjects, MHO had a higher odds of CAC (OR 1.36, 95% CI [1.11 to 1.66]; I2 = 39%). In the subgroup analysis, the risk associated with MHO participants was significant in cohort studies (OR = 1.47, 95% CI [1.15,1.87], I2 = 0%), and borderline significant in cross-sectional studies. The risk of CAC was also significant in MHO participants defined by Adult Treatment Panel III (ATP III) (OR = 1.55, 95% CI [1.25,1.93], I2 = 0%). The univariate meta-regression model showed that age and smoking status were possible effect modifiers for MHO and CAC risk.ConclusionOur meta-analysis showed that MHO phenotypes were associated with elevated risk of CAC compared with MHNO, which reflects the extent of coronary atherosclerosis. People with obesity should strive to achieve normal weight even when only one metabolic abnormality is present.