Metabolically Abnormal Obese Research Articles

Associations of metabolic heterogeneity of obesity with the risk of dementia in middle-aged adults: three prospective studies

BackgroundThe associations of different obesity and metabolic phenotypes during midlife with the risk of incident dementia remain unclear. This study aimed to investigate the associations between metabolic heterogeneity of obesity and long-term risk of dementia.MethodsWe conducted prospective analyses from three cohorts, including the UK Biobank (UKB), Atherosclerosis Risk in Communities (ARIC) study, and Framingham Offspring Study (FOS). Eligible participants were those aged 45–65 years with valid assessments of body mass index (BMI) and metabolic status at the study baseline. Obesity was defined as a BMI of ≥ 30.0 kg/m2, while metabolic abnormality was defined as meeting ≥ 2 of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria. Metabolic heterogeneity of obesity was evaluated based on obesity and metabolic phenotypes and grouped as metabolically normal non-obesity (MNNO), metabolically abnormal non-obesity (MANO), metabolically normal obesity (MNO), and metabolically abnormal obesity (MAO).ResultsIncluded in this study were 295,823 participants aged 56.3 ± 5.9 years from the UKB, 12,547 participants aged 54.0 ± 5.7 years from the ARIC, and 2,004 participants aged 53.9 ± 5.9 years from the FOS. Over 4,348,208 person-years, a total of 6,190 participants (3,601 in the UKB, 2,405 in the ARIC, and 184 in the FOS) developed incident dementia. In the pooled analysis of three cohorts, metabolic abnormality was associated with a hazard ratio (HR) of 1.41 (95% confidence interval [CI]: 1.10–1.80) for dementia, while obesity was associated with an HR of 1.20 (1.03–1.41). Compared with MNNO, individuals with MANO and MAO had increased risks of dementia (pooled HR: 1.33, 95% CI: 1.04–1.71 for MANO and 1.48, 1.16–1.89 for MAO). However, there was no significant difference in the risk of dementia among MNO (pooled HR: 1.10, 95% CI: 0.98–1.24). In addition, participants who recovered from MANO to MNNO had a lower risk of dementia (pooled HR: 0.79, 95% CI: 0.64–0.97), as compared with stable MANO.ConclusionsMetabolic abnormality has a stronger association with dementia than obesity. Metabolically abnormal non-obesity and obesity, but not metabolically normal obesity, are associated with higher risks of incident dementia as compared with metabolically normal non-obesity. Recovering from an abnormal metabolic status to normal reduces the risk of dementia in populations without obesity. Our findings highlight the important role of metabolic status in the development of dementia and recommend the stratified management of obesity based on metabolic status.

Effect of Obesity and Metabolic Health Status on Metabolic-Associated Steatotic Liver Disease among Renal Transplant Recipients Using Hepatic Steatosis Index

Background/Objectives: Obesity and metabolic conditions increase the risk of metabolic-associated steatotic liver disease (MASLD). This study examined the risk of MASLD in 137 renal transplant recipients (RTRs) from a single-center hospital on the basis of their obesity and metabolic health status. Methods: Participants were categorized into four groups: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically abnormal nonobese (MANO), and metabolically abnormal obese (MAO). MASLD was assessed using the hepatic steatosis index (HSI), calculated as 8 × (aspartate aminotransferase/alanine aminotransferase ratio) + body mass index + 2 (if diabetic) + 2 (if woman). The HSI scores were 29.50 ± 4.55, 38.08 ± 5.44, 33.61 ± 5.23, and 39.86 ± 4.13 in the MHNO, MHO, MANO, and MAO groups, respectively (p < 0.05). Results: Overall, 25.55% of the participants (57.14% men) were classified as having MASLD (HSI > 36). A multivariate-adjusted regression analysis revealed significantly higher HSI scores in the MAO group than in the MHNO group. Both MHO and MANO groups also had significantly higher HSI scores. The odds ratios for more severe MASLD were 2.74 (95% CI: 0.88–8.52) for the MANO group and 74.59 (95% CI: 13.29–418.68) for the MAO group compared with the MHNO group. Conclusions: These findings suggest that RTRs with obesity have a higher risk of MASLD, but even those with a normal weight and metabolic abnormalities are at increased risk.

Association of Metabolically Healthy Obesity and Risk of Cardiovascular Disease Among Adults in China: A Retrospective Cohort Study

Previous studies have shown that metabolically healthy obesity (MHO) and changes in its status are connected to an increased incidence of cardiovascular disease (CVD). Yet, fewer studies have been conducted in China, especially for the middle-aged and elderly population, a high-risk group. The purpose of the study was to investigate the association between metabolic health status and CVD events. A total of 46,055 participants were categorized into 6 subgroups with different metabolic states according to the existence of metabolic syndrome and body mass index (BMI). The changes in obesity and metabolic health status were defined from baseline to follow-up outcomes with a combination of overweight and obesity. Cox proportional hazards models estimated the association of CVD events and each BMI-metabolic groups. MHO and metabolic abnormality normal weight (MANW) subjects had a higher HR of CVD, 1.62 (95% CI, 1.36-1.92) and 1.24 (95% CI, 1.07-1.44), respectively, than their metabolically healthy normal weight (MHNW) counterparts. Then, more than 50% and 30% of the metabolically healthy overweight or obesity (MHOO) populations maintained their status and converted to a metabolically unhealthy state, respectively. Stable MANW, MHOO and metabolically abnormal obesity (MAO) were associated with a higher risk for CVD, 1.68 (95% CI, 1.37-2.05),1.26 (95% CI, 1.08-1.47) and 1.65 (95% CI, 1.45-1.88), respectively, than stable MHNW. Despite being of normal weight, MANW status is in fact a risk factor for CVD, as well as MHO, especially for the Chinese middle-aged and elderly population. Furthermore, metabolic health is a transient state for partial middle-aged and elderly Chinese individuals, and MAO has the highest risk of CVD, including coronary heart disease (CHD) and stroke.

Differences of Regional Fat Distribution Measured by Magnetic Resonance Imaging According to Obese Phenotype in Koreans.

Background: Obesity is commonly associated with a high risk of metabolic disorders, and obesity-related metabolic abnormalities are affected by some specific obesity phenotypes, regional fat distribution, and body mass index. However, few studies have investigated the relationship between obesity phenotypes and regional fat distribution in Korean subjects. This study aimed to assess regional fat distribution by gender using magnetic resonance imaging (MRI), and to identify a link between fat distribution and metabolic disorders in Korean subjects. Methods: This study included 35 Korean subjects (20 women, 15 men) who were classified into two groups by gender, and further divided into two groups based on their obesity phenotype: a metabolically abnormal obesity (MAO) and metabolically healthy obesity (MHO) group. Fat distribution was measured using MRI. The blood parameters were measured using a commercially available kit. Results: Women in the MAO group had more risk factors for metabolic abnormalities than those in the MHO group. Serum glucose, triglyceride, and high-density lipoprotein cholesterol (HDL-C) levels were also significantly higher in women with MAO than in those with MHO. The intermuscular adipose tissue (IMAT) of women with MAO was significantly higher than that of women with MHO. Serum HDL-C level was negatively correlated with IMAT, whereas leptin showed a positive correlation with IMAT in all subjects. Conclusions: Metabolic abnormalities according to obesity phenotype posed a higher risk in women than that in men. These findings suggest that an understanding of gender differences in relation to the association between obesity and metabolic risk would be helpful to reduce the prevalence of obesity.

Abnormal Obesity Phenotype Is Associated with Reduced eGFR among Diabetes Mellitus and Hypertensive Patients in a Peri-Urban Community in Ghana.

Background Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia due to obesity and defects in insulin action. Significant complications of DM include kidney disease due to its association with hypertension and obesity. Thus, the contribution of the various obesity phenotypes to the kidney impairment observed among hypertensive and diabetes mellitus patients is of major concern. Aim The study assessed the association between obesity phenotypes and reduced glomerular filtration rate among diabetes mellitus and hypertensive patients. Methods Three hundred and ten (310) adult patients diagnosed with type 2 diabetes mellitus, hypertension, or both who attended the Presbyterian Hospital, Dormaa Ahenkro, from October 2016 to March 2017 were recruited for the study. Blood samples were collected to analyze biochemical parameters (fasting blood glucose (FBG), lipid profile, and creatinine). Questionnaires were used to collect sociodemographic information, and anthropometrics were appropriately measured. The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation, and reduced eGFR was defined as eGFR <90 ml/min/1.73 m2. Results The prevalence of metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically abnormal nonobese (MANO), and metabolically abnormal obese (MAO) phenotypes among the study participants was 30.65%, 4.50%, 52.90%, and 11.94%, respectively. The highest prevalence of reduced eGFR (29/37 (78.38%)) was seen among the MAO group. This was followed by the MANO, MHO, and MHNO with a reduced eGFR prevalence of 62.20%, 57.64%, and 37.89%, respectively. After normalization with MHNO, the reduced eGFR was 1.51, 1.64, and 2.06 times expressed in MHO, MANO, and MAO. For the total samples, when MHNO was maintained as a reference, reduced eGFR was significantly associated with MANO (aOR = 3.07 (95% CI = 1.76–5.35), P < 0.001) and MAO (aOR = 5.67 (95% CI = 2.66–17.27), P < 0.001) even after adjusting for age, gender, smoking, and alcohol intake. This association was maintained among the female study participants when stratified by gender, and in addition, among the female participants, reduced eGFR was also associated with MHO (aOR = 4.19 (95% CI = 1.06–16.53), P=0.041). Conclusion There is a high prevalence of abnormal metabolic phenotypes among diabetes mellitus patients, and these were significantly associated with reduced eGFR among our study participants.

Poor sleep and the metabolic derangements associated with obesity in adult males

ABSTRACTContext:Short sleep and obesity have a causal association with each other. Obesity is also associated with metabolic imbalances. However, a subset of 20%–30% of obese population have only few metabolic complications, known as metabolically healthy obese (MHO) and rest with worsened metabolic profile are known as metabolically abnormal obese (MAO)Aims:To find the association between sleep quality and metabolic health of adult obese males.Settings and Design:The study was a cross-sectional study conducted at medicine out-patient department of the institute.Methods and Material:In this study, hundred adult obese males of age group 25–60 years, with Body mass index (BMI) ≥ 25 Kg/m2, were divided into MHO and MAO, based on their metabolic health using Joint Interim criteria. Sleep quality was assessed using Pittsburgh sleep questionnaire index (PSQI).Statistical analysis used:The data obtained were analyzed using PAST statistical softwareResults:The two groups MHO and MAO presented with significant differences in their mean age and BMI (P = 0.0001). The global score of PSQI was significantly high for MAO than MHO with mean values of 8.24 ± 3.60 and 6.65 ± 3.58, respectively (P = 0.016). Sleep disturbances score was significantly high in MAO (P = 0.0001). Significant associations were observed for global score with age, BMI, waist circumference, fasting blood sugar, and triglyceridesConclusions:Poor sleep quality was significantly associated with detrimental metabolic profile and BMI. The metabolic health worsened with increasing age and obesity.

Effects of body size phenotype on sleep quality in middle-aged Korean men

Background: Research on body size phenotype according to metabolic syndrome and obesity is being actively conducted. Quality of sleep can vary depending on the body size phenotype. This study aimed to investigate the effects of body size phenotype on sleep quality in middle-aged Korean men. Methods: This study used secondary data analysis from a community-based cohort of the Korean Genome and Epidemiology Study (KoGES). Using BMI and metabolic health status, among 3675 men aged between 40 and 65 years, body size phenotypes were classified as follows: metabolically healthy normal weight (MHNW) (50.8%), metabolically healthy obesity (MHO) (32.5%), metabolically abnormal obesity (MAO) (12.7%), and metabolically abnormal but normal weight (MANW) (4.0%). Results: MANW men had the most prolonged sleep duration (more than 7 hours), and MHO men had the shortest sleep duration. The degree of difficulty falling back to sleep after waking in MHO men was 0.76 times that of MHNW men (p = 0.02). Conclusions: Sleep duration and difficulties falling back to sleep were independently associated with body size phenotype in middle-aged men after adjusting for confounding factors. Health professionals and officials in labor departments may use the results of this study to improve the quality of sleep and ultimately help with productivity in the workplace.

Increased Stroke Risk in Metabolically Abnormal Normal Weight: a 10-Year Follow-up of 102,037 Participants in China.

The purpose of this study was to investigate the risks of stroke in subjects with metabolically abnormal normal weight (MANW) in China. We recruited 102,037 participants from the Zhejiang Metabolic Syndrome Cohort and the Kailuan cohort. The mean years of follow-up were 9.9years. General obesity was defined by body mass index (BMI) ≥ 28, overweight by BMI < 28 and ≥ 24, and normal weight by BMI < 24 and ≥ 18.5. Metabolic abnormality was defined as two or more abnormal components (elevated triglycerides, low high-density lipoprotein cholesterol, elevated systolic blood pressure or diastolic blood pressure, or use of antihypertensive drug therapy, elevated fasting plasma glucose, or antidiabetic treatment). A multiple Cox regression model was used to calculate hazard ratio (HR) and its 95% confidence interval (CI), adjusted by potential confounding factors. Overall HR of the risks in two cohorts was calculated by a meta-analysis. Compared with the subjects who were metabolically normal with normal weight (MNNW), the pooled HR for stroke in MANW subjects was 1.82 (95% CI, 1.59-2.07). The risks of stroke in MANW subjects were significantly lower than that in subjects with metabolically abnormal obesity (MAO), but higher than that in those with metabolically normal obesity (MNO) (P < 0.05). These associations remained in the subtypes of cerebral infarction and cerebral hemorrhage. In normal-weight subjects, the HR for stroke was significantly positively correlated with the number of abnormal metabolic components (Ptrend < 0.001). In brief, metabolic abnormality increased the risk of stroke irrespective of obesity status. MANW individuals showed a greater risk of stroke, and this risk was positively correlated with the number of abnormal metabolic components.

Comparing an adiposopathy approach with four popular classifications schemes to categorize the metabolic profile of postmenopausal women.

Numerous classifications are used to discern metabolically healthy obese (MHO) from metabolically abnormal obese (MAO) individuals. The goal of this study was to compare a single phenotype approach, adiposopathy (i.e., the plasma adiponectin/leptin ratio), with four commonly used classifications (International Diabetes Federation (IDF), Karelis, Lynch, Wildman), all based on obesity with other risk factors), for their ability to discern phenotypic differences between MAO and MHO postmenopausal women. Anthropometry, body composition, blood pressure, cardiorespiratory fitness (CRF), lipid-lipoprotein, hepatic, inflammatory, and adipokine profiles, as well as glucose-insulin homeostasis, were assessed in 79 obese sedentary postmenopausal women (60 ± 5years; body mass index, BMI, 34.0 ± 3.7kg/m2). Abdominal subcutaneous adipose tissue (SCAT) expression of selected genes involved in fatty acid metabolism and inflammation was used as markers of tissue state (n= 48). Beyond their intrinsic criteria, adiposopathy was almost as effective as the Karelis definition in discerning differences in MHO for adiposity (reduced body weight, BMI, waist circumference, and fat mass), lipid-lipoprotein (lower triacylglycerol and higher HDL-cholesterol levels, reduced atherogenic ratios) and adipokine (higher adiponectin and lower leptin levels) profiles, and glucose-insulin homeostasis (lower insulin resistance) as well as for some SCAT gene expression related to lipolysis and lipogenesis, but was the only one able to distinguish these subjects for greater CRF. The other classifications revealed fewer differences between MAO and MHO women. These data suggest that considering a marker of AT dysfunction such as adiposopathy either alone or in addition to other criteria could be potentially interesting in discerning the MHO phenotype.

Schizophrenia patients with a metabolically abnormal obese phenotype have milder negative symptoms

BackgroundSchizophrenia patients with a metabolically abnormal obese (MAO) phenotype have been shown poor cardiovascular outcomes, but the characteristics of their current psychiatric symptoms have not been characterized. This study mainly explored the psychiatric symptoms of schizophrenia patients with the MAO phenotype.MethodsA total of 329 patients with schizophrenia and 175 sex- and age-matched people without schizophrenia from Anhui Province in China were enrolled. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms of the schizophrenia patients. The MAO phenotype was defined as meeting 1–4 metabolic syndrome criteria (excluding waist circumference) and having a body mass index (BMI) ≥ 28 kg/m2. And, metabolically healthy normal-weight (MHNW) phenotype was defined as meeting 0 criteria for metabolic syndrome and 18.5 ≤ BMI < 24 kg/m2.ResultsOverall, 15.8% of the schizophrenia patients and 9.1% of the control group were consistent with the MAO phenotype, and the prevalence of MAO in the schizophrenia group was higher than that in the control group. Among the patients with schizophrenia, the MAO group had lower negative factor, cognitive factor and total PANSS scores than the MHNW group. However, when confounding factors were controlled, only the negative factor remained lower significantly.ConclusionWe found that schizophrenia patients with the MAO phenotype had reduced negative symptoms, which may indicate an internal mechanism linking metabolic disorders and negative symptoms.Trial registrationThis study was registered in the China Clinical Trial Registration Center (No. chiCTR 1,800,017,044).

Serum ZAG and Adiponectin Levels Were Closely Related to Obesity and the Metabolically Abnormal Phenotype in Chinese Population.

IntroductionTo explore serum zinc-α2-glycoprotein (ZAG) and adiponectin in metabolically healthy non-obese (MHNO), metabolically healthy obesity (MHO), metabolically abnormal obesity (MAO) and metabolically abnormal diabetic obese (MADO) subjects and the relationship with metabolically phenotypes of obesity.MethodsTwo hundred twenty-five subjects including 32 with MHNO, 40 with MHO, 104 with MAO and 49 with MADO were enrolled. Baseline clinical data and biochemical variables were collected. Serum ZAG and adiponectin levels were measured by enzyme-linked immunosorbent assay (ELISA) kits. Metabolically healthy (<3 metabolic abnormalities) or abnormal (≥3 metabolic abnormalities) subjects were classified based on the National Cholesterol Education Program–Adult Treatment Panel III (NCEP/ATP III) criteria. Obesity (body mass index ≥28 kg/m2) was recommended by China Obesity Task Force.ResultsSerum ZAG levels were higher in the MHO group, but were progressively lower in MAO and MADO groups (P all<0.05). In all subjects, total cholesterol, 2-hour postprandial blood glucose and homeostasis model assessment of adiponectin were independent variables to serum ZAG levels. Compared with subjects in the highest tertile of ZAG, the odds ratio (OR) of metabolically abnormal risks of subjects in the lowest and median tertiles of ZAG were higher both in a univariate and three adjustment models (P all<0.05). Serum ZAG could discriminate the metabolically abnormal phenotype with receiver operating characteristic (ROC) curve area of 0.622 (95% CI, 0.539–0.706, P<0.05). Combination of ZAG and adiponectin had improved diagnosis value accuracy, with ROC curve area of 0.703 (95% CI, 0.629–0.776, P<0.05), and 62.7% sensitivity and 73.6% specificity.ConclusionSerum ZAG levels were higher in MHO subjects, but lower in MAO and MADO subjects. The decreased serum ZAG levels were closely related to the metabolically abnormal phenotype of obese patients. Serum ZAG, especially the combination with adiponectin might be the potential diagnostic biomarkers for metabolically abnormal obese patients.

Prevalence of NASH/NAFLD in people with obesity who are currently classified as metabolically healthy.

While metabolic health in obesity may confer a protective status, recent studies indicate that nonalcoholic fatty liver disease (NAFLD) or even nonalcoholic steatohepatitis (NASH) may exist in this category of individuals. Although cardiovascular and diabetic risks have been well described, the risk of NAFLD and NASH among this population requires further investigation. Our goal was to compare the prevalence of steatosis, NAFLD, and NASH between individuals with metabolically healthy obesity (MHO) and individuals with metabolically abnormal obesity (MAO) and to identify preoperative risk factors for these conditions in a prospective cohort with morbid obesity scheduled for bariatric surgery. Tertiary referral university hospital in France. The prospective cohort included 837 bariatric patients who also had an intraoperative liver biopsy between 2002 and 2015. Obese individuals fulfilling none of the criteria in the strict definition of metabolic syndrome were considered metabolically healthy. Preoperative blood samples and liver pathology examinations were reviewed. Steatosis, NAFLD, and NASH were carefully identified allowing comparison of prevalence and risk factors between the 2 cohorts. In total, 149 patients (17.8%) had MHO and the remaining 688 (82.2%) had MAO. The cohort with MHO was significantly younger, had a significantly lower glycosylated hemoglobin, a lower homeostasis model assessment of insulin resistance, and increased C-reactive protein. In individuals with MHO, 44 patients (29.5%) had at least moderate steatosis (>33% macrovesicular steatosis) and 5.4% had NASH. Using logistic regression, waist circumference was positively associated with NASH, whereas body mass index and alanine aminotransferase were significantly associated with severe steatosis (>66%). Our study indicates that obese individuals without metabolic syndrome may develop subclinical liver involvement. Therefore, the occurrence of NAFLD and NASH in this population needs further investigation.

Metabolically Healthy Obesity and Risk of Incident Chronic Kidney Disease in a Korean Cohort Study

The incident of chronic kidney disease (CKD) of metabolically healthy obesity (MHO) has not been consistently determined. This study used data of Anseong Ansan community-based cohort, a part of the Korean Genome and Epidemiology Study (KoGES) provided by the Korea Center for Disease Control and Prevention (KCDC). Surveys were received from the Anseung and Ansan residents every two years between 2001-2002 and 2015-2016 for a total of 7 surveys over all. The subjects were divided into 4 phenotypes based on the presenting obesity and metabolic syndrome; 1) metabolically healthy normal weight (MHNW), 2) metabolically healthy obesity (MHO), 3) metabolically abnormal normal weight (MANW), and 4) metabolically abnormal obesity (MAO). Data were analyzed using the Cox proportional hazards regression model. Of 8,865 subjects, 1,551 cases of 49,995 person-year (3.1%) developed incident CKD. At an adjusted hazard ratio (HR) of 1.13, the MHO group was not associated with a higher risk of incident CKD (95% confidence interval (CI): 0.92-1.41, P =0.234, using MHNW as the reference). The adjusted HRs of the MANW and MAO groups for incident CKD were significantly higher than those of the MHNW groups: 1.31 (95% CI: 1.05-1.64, P=0.017) for MANW and 1.49 (95% CI: 1.23-1.79, P<0.001) for MAO. MHO is not associated with a high risk of CKD, and that MANW and MAO increase the risk of the incident CKD. Thus, it is important to consider metabolic health status rather than obesity when evaluating CKD risk.

Associations between obesity and metabolic health with nonalcoholic fatty liver disease in elderly Chinese

BackgroundNonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. However, this association could be influenced by the coexisting metabolic abnormalities. This study aimed to investigate the role of obesity and metabolic abnormalities in NAFLD among elderly Chinese. MethodsA cross-sectional study was performed among elderly residents who took their annual health checkups during 2016 in Keqiao District, Shaoxing, China. ResultsA total of 3359 elderly adults were retrospectively included in this study. The overall prevalence of NAFLD was 28.7%. The prevalence of NAFLD were 7.14%, 27.92%, 34.80%, and 61.02% in participants with metabolically healthy normal weight (MHNW), metabolically abnormal normal weight (MANW), metabolically healthy obese (MHO), and metabolically abnormal obese (MAO), respectively. NAFLD patients in MHO group had more unfavorable metabolic profiles than those in MHNW group. Logistic regression analysis showed that sex, body mass index (BMI), fasting blood glucose, and serum uric acid were the risk factors of NAFLD. ConclusionsBoth obesity and metabolic health were significantly associated with NAFLD in elderly Chinese. Screening for obesity and other metabolic abnormalities should be routinely performed for early risk stratification of NAFLD.

Impact of metabolically healthy obesity on the risk of incident gastric cancer: a population-based cohort study

BackgroundThe risk of colon or breast cancer in metabolically healthy obese (MHO) were lower than that in metabolically abnormal obese (MAO). We hypothesized that the risk of incident gastric cancer in MHO is lower than that in MAO.MethodsThis historical cohort study included 19,685 Japanese individuals who received health-checkup programs from 2003 to 2016. Each subject was classified as metabolically healthy (MH) (no metabolic abnormalities) or metabolically abnormal (MA) (one or more metabolic abnormalities), according to four metabolic factors (hypertension, impaired fasting glucose, hypertriglyceridemia and low HDL-cholesterol). Obese (O) or non-obese (NO) was classified by a BMI cutoff of 25.0 kg/m2. Hazard ratios of metabolic phenotypes for incident gastric cancer were calculated by the Cox proportional hazard model with adjustments for age, sex, alcohol consumption, smoking and exercise.ResultsOver the median follow-up period of 5.5 (2.9–9.4) years, incident rate of gastric cancer was 0.65 per 1000 persons-years. Incident rate of MHNO, MHO, MANO and MAO were 0.33, 0.25, 0.80 and 1.21 per 1000 persons-years, respectively. Compared with MHNO, the adjusted hazard ratios for development of gastric cancer were 0.69 (95% CI 0.04–3.39, p = 0.723) in MHO, 1.16 (95% CI 0.63–2.12, p = 0.636) in MANO and 2.09 (95% CI 1.10–3.97, p = 0.024) in MAO.ConclusionsThis study shows that individuals with MAO, but not those with MHO, had an elevated risk for incident gastric cancer. Thus, we should focus more on the presence of metabolic abnormalities rather than obesity itself for incident gastric cancer.

Strong association between metabolically-abnormal obesity and gallstone disease in adults under 50\u2009years

BackgroundAge, obesity, and metabolic syndrome are known risk factors for gallstones; however, the combined impact of these different risk factors on gallstone formation has not yet been examined.MethodsThis retrospective, cross-sectional study involved 3190 participants, including 207 participants (6.5%) with gallstones and 986 (30.9%) with metabolic syndrome. Participants were divided into four phenotypes according to metabolic syndrome and obesity status: 1378 participants were metabolically healthy and non-obese (MHNO); 826 were metabolically healthy but obese (MHO); 185 were metabolically abnormal but not obese (MANO); and 801 participants were metabolically abnormal and obese (MAO).ResultsThe MAO and MANO phenotypes had more gallstones than the MHO and MHNO phenotypes, regardless of age (< 50 or ≥ 50 years old). Multivariate analyses showed that phenotype was an independent risk factor for gallstones in participants < 50 years old (odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.32–2.28). Younger participants also had a higher risk of gallstones in the MAO (OR = 5.41, 95% CI = 2.31–12.66), MANO (OR = 3.18, 95% CI = 0.86–11.75), and MHO (OR = 2.17, 95% CI = 0.90–5.22) phenotypes than the MHNO phenotype.ConclusionsOur retrospective results demonstrate an increased association of gallstones in younger people (< 50 years old) with metabolic syndrome and obesity.

3068 Effects of exercise and a very low fat diet in metabolically abnormal obese adults

OBJECTIVES/SPECIFIC AIMS: People with metabolically abnormal obesity (MAO), defined as those with insulin resistance and high intrahepatic triglyceride, are at high risk for developing type 2 diabetes and cardiovascular disease. Weight loss through reduced energy intake and increased physical activity has profound impacts on improving cardiometabolic function. However, the specific additional effects of exercise training with diet-induced weight loss on metabolic function are equivocal. METHODS/STUDY POPULATION: A comparative trial is ongoing in MAO adults undergoing 8-10% weight loss induced by a very-low fat plant-based (PB) diet with structured exercise training (n=8) compared to the same weight loss induced by the PB diet alone (n=3). RESULTS/ANTICIPATED RESULTS: Preliminary results indicate that, PB diet with or without exercise training results in significant weight loss concomitant with enhanced insulin sensitivity, reduced intrahepatic triglyceride, reduced 24-hour postprandial glucose response, reduced fat mass, and reduced diastolic blood pressure. Those undergoing PB diet with exercise training had greater improvements in muscular strength and cardiorespiratory fitness than those undergoing PB diet alone. Differences between intervention groups for other cardiometabolic measures are not yet known. DISCUSSION/SIGNIFICANCE OF IMPACT: Each of the interventions resulted in improved cardiometabolic measures; however the extent of the differences between the interventions is not yet clear. It is hypothesized that compared with weight loss induced by a PB diet, the same weight loss induced by a PB diet and structured exercise training will i) cause greater improvement in skeletal muscle insulin sensitivity, ii) will attenuate the usual decline in muscle mass while increasing strength, and iii) result in greater increases in left ventricular diastolic function. The long-term objective of this proposal is to provide a foundation for future studies evaluating mechanisms for the effects of exercise in cardiometabolic disease prevention and therapy.

Differences in dietary intakes, body compositions, and biochemical indices between metabolically healthy and metabolically abnormal obese Korean women.

BACKGROUND/OBJECTIVESThere are various factors that affect metabolic abnormalities related to obesity. The purpose of this study is to analyze the differences in dietary intakes and body compositions of obese women according to metabolic risks and to classify them as metabolically healthy obese (MHO) or metabolically abnormal obese (MAO).SUBJECTS/METHODSThis study was conducted on 59 obese Korean women aged 19 to 60 years. NCEP-ATPIII criteria were applied and the women classified as MHO (n = 45) or MAO (n = 14). Body composition of each subject was measured by using dual-energy x-ray absorptiometry (DEXA). Three-day food records were used to analyze dietary intake. Eating habits and health-related behaviors were determined through questionnaires. Indirect calorimetry was used to measure resting metabolic rate and respiratory rate.RESULTSThe average age of the subjects was 43.7 years. The analysis of body composition according to phenotype revealed significantly higher body fat mass (P < 0.05), arm fat mass (P < 0.05), and android fat mass (P < 0.05), as measured by DEXA, in the MAO group than in the MHO group. There was no significant difference in the dietary intake of the two groups. However, eating behaviors differed. Compared to the MHO group, the MAO women had a shorter meal time (less than 10 minutes), a preference of oily foods, and a tendency to eat until full. Therefore, the eating habits of MHO women were more positive than those of MAO women.CONCLUSIONSThe results suggest that fat distribution in each body region affects various metabolic abnormalities. A high level of arm fat mass in obese Korean women may increase metabolic risk. In addition, eating habits of obese Korean women are considered to be environmental factors affecting the metabolic phenotype of obese Korean women.

Changes in obese metabolic phenotypes over time and risk of incident chronic kidney disease

To examine the association between metabolically healthy obese (MHO) phenotype and incident chronic kidney disease (CKD) and study whether changes in metabolic phenotypes over time could affect CKD risk. A total of 8589 subjects from the Korean Genome and Epidemiology Study were categorized into four groups based on the presence of obesity and metabolic abnormalities (MA). The primary endpoint was an onset of incident CKD defined as an estimated glomerular filtration rate of ≤ 60 mL/min/1.73 m2 . Multivariable Cox analysis and time-varying Cox analysis were performed to delineate the relationship between obese metabolic phenotypes and incident CKD after adjustment for sociodemographic factors and clinical and laboratory parameters. During a mean follow-up duration of 9.3 years, CKD occurred in 782 (9.1%) participants. In the multivariable Cox model, the hazard ratio (HR) for incident CKD in the MHO, metabolically abnormal non-obese (MANO), and metabolically abnormal obese (MAO) groups was 1.42 (P = 0.002), 1.45 (P < 0.001), and 1.77 (P < 0.001), respectively, compared with the metabolically healthy non-obese (MHNO) group. Time-varying analysis with these four phenotypes as time-varying exposures showed the same results. Furthermore, subjects with persistent MHO through follow-up were at a 2.0-fold increased risk of CKD (P < 0.001). 41.0% of subjects experienced phenotype changes during follow-up. Over the long term, the MHO group had a higher proportion of transition to the MA phenotype and unfavourable metabolic profiles than the MHNO group. Among MHO subjects, those who transitioned to MAO were at a 4.1-fold increased risk of incident CKD than those who regressed to MHNO. In addition, transition to MHO from other groups carried a higher risk of CKD than persistent MHNO. MHO subjects are at increased risk for incident CKD.

Whole-genome transcriptomic insights into protective molecular mechanisms in metabolically healthy obese African Americans

Several clinical guidelines have been proposed to distinguish metabolically healthy obesity (MHO) from other subgroups of obesity but the molecular mechanisms by which MHO individuals remain metabolically healthy despite having a high fat mass are yet to be elucidated. We conducted the first whole blood transcriptomic study designed to identify specific sets of genes that might shed novel insights into the molecular mechanisms that protect or delay the occurrence of obesity-related co-morbidities in MHO. The study included 29 African-American obese individuals, 8 MHO and 21 metabolically abnormal obese (MAO). Unbiased transcriptome-wide network analysis was carried out to identify molecular modules of co-expressed genes that are collectively associated with MHO. Network analysis identified a group of 23 co-expressed genes, including ribosomal protein genes (RPs), which were significantly downregulated in MHO subjects. The three pathways enriched in the group of co-expressed genes are EIF2 signaling, regulation of eIF4 and p70S6K signaling, and mTOR signaling. The expression of ten of the RPs collectively predicted MHO status with an area under the curve of 0.81. Triglycerides/HDL (TG/HDL) ratio, an index of insulin resistance, was the best predictor of the expression of genes in the MHO group. The higher TG/HDL values observed in the MAO subjects may underlie the activation of endoplasmic reticulum (ER) and related-stress pathways that lead to a chronic inflammatory state. In summary, these findings suggest that controlling ER stress and/or ribosomal stress by downregulating RPs or controlling TG/HDL ratio may represent effective strategies to prevent or delay the occurrence of metabolic disorders in obese individuals.