Metabolically Abnormal Obese Research Articles

Association of metabolically abnormal but normal weight (MANW) and metabolically healthy but obese (MHO) individuals with arterial stiffness and carotid atherosclerosis

ObjectiveDespite recent interest in differential impact of body size phenotypes on cardiovascular outcomes and mortality, studies evaluating the association between body size phenotypes and indicators of atherosclerosis are limited. This study investigated the relationship of metabolically abnormal but normal weight (MANW) and metabolically healthy but obese (MHO) individuals with arterial stiffness and carotid atherosclerosis in Korean adults without cardiovascular disease. MethodsA total of 1012 participants (575 men and 437 women, mean age 50.8 years), who underwent a health examination between April 2012 and May 2013 were prospectively enrolled based on inclusion and exclusion criteria. Study subjects were classified according to body mass index (BMI) and the presence/absence of metabolic syndrome. ResultsThe prevalence of metabolically healthy normal weight (MHNW), MANW, MHO, and metabolically abnormal obese (MAO) were 54.84%, 6.42%, 22.83%, and 15.91%, respectively. Individuals with MANW had significantly higher brachial-ankle pulse wave velocity and maximal carotid intima-media thickness values than those with MHO, after adjusting for age and gender (P = 0.026 and P = 0.018, respectively). The odds ratio (OR) of arterial stiffness and carotid atherosclerosis in the MANW group were significantly higher than in the MHNW group in unadjusted models. Furthermore, multivariable models showed that increased OR of carotid atherosclerosis in the MANW group persisted even after adjusting for confounding factors (OR = 2.98, 95% CI = [1.54, 5.73], P = 0.011). ConclusionsCompared to MHNW or MHO subjects, Korean men and women with the MANW phenotype exhibited increased arterial stiffness and carotid atherosclerosis. Clinical trials noNCT01594710.

The Metabolically Healthy But Obese Phenotype Is Associated With Lower Plasma Levels of Persistent Organic Pollutants as Compared to the Metabolically Abnormal Obese Phenotype

Although obesity is strongly linked to insulin resistance and type 2 diabetes, a subset of obese individuals termed metabolically healthy but obese (MHO) appears relatively protected from the development of cardiometabolic complications. The origins of this metabolically healthy phenotype remain unclear. Recently, persistent organic pollutants (POPs) have emerged as potential endocrine disruptors. The aim of this study was to test the hypothesis that the MHO phenotype presents lower circulating levels of POPs as compared to the metabolically abnormal obese (MAO) phenotype. We conducted a cross-sectional study of 76 nondiabetic obese (body mass index ≥30 kg/m(2)) postmenopausal women. Plasma concentrations of 21 POPs as well as cardiometabolic risk factors were analyzed. For similar age, body mass index, and fat mass index, MHO women (n = 40) showed higher insulin sensitivity levels and a more favorable cardiometabolic profile than MAO women (n = 36), as evidenced by a 2-fold increase in glucose disposal rates measured by the hyperinsulinemic-euglycemic clamp (P = .001). Among 18 detectable pollutants measured, MAO women had higher plasma concentrations of 12 POPs (fold increase, 1.4-2.9; P < .001-.036). Logistic regression analyses showed that the prevalence of the MAO phenotype was significantly associated with higher levels of total dioxin- and non-dioxin-like polychlorinated biphenyls (odds ratio, 4.7; 95% confidence interval, 1.8-12.5; P = .002), as well as trans-nonachlor (odds ratio, 6.1; 95% CI, 2.2-16.4; P < .001). Our study demonstrates that the metabolically healthy and abnormal phenotypes have distinct plasma POP profiles.

Metabolically healthy obese subjects are at risk of fatty liver but not of pre-clinical atherosclerosis

Backgrounds and aimsWhether obesity increases risk of cardiovascular disease (CVD) and fatty liver because of the co-existence of other risk factors is uncertain. We investigated odds ratios (ORs) for: a) a measure of pre-clinical atherosclerosis and b) fatty liver, in metabolically healthy obese (MHO) subjects, metabolically abnormal obese (MAO) subjects and metabolically abnormal non obese subjects (MANO), using a metabolically healthy non obese (MHNO) group as the reference. Methods and results14,384 South Koreans from an occupational cohort underwent cardiac computed tomography (CT) estimation of CAC score, liver ultrasound determination of fatty liver, and measurement of cardiovascular risk factors. Pre-clinical atherosclerosis was defined by a CAC score >0. We used logistic regression to determine ORs for CAC >0, and fatty liver in MHO, MAO and MANO subjects (reference group MHNO). There was no increase in OR for CAC score >0 (OR = 0.93, [95% CIs 0.67,1.31], p = 0.68), in the MHO group, whereas there was an increase in the ORs for CAC score >0 in the MAO, and MANO groups (OR = 1.64 [95% CI 1.36,1.98], p < 0.001) and (OR = 1.38 [95% CI 1.17,1.64], p < 0.001), respectively. In contrast, for fatty liver, there was an increase in OR in each group (OR = 3.63 [95% CI 3.06, 4.31] p < 0.001); (OR = 5.89 [5.18,6.70] p < 0.001); and (OR = 1.83 [95% CI 1.69,2.08]) in the MHO, MAO group and MANO groups respectively. ConclusionMHO subjects are at risk of fatty liver but attenuated risk of pre-clinical atherosclerosis. Both MAO and MANO subjects are at risk of fatty liver and pre-clinical atherosclerosis.

Prevalence of Metabolically Discordant Phenotypes in a Mediterranean Population—the Imap Study

To study the prevalence and correlates of body size phenotypes in an adult Spanish population. We undertook a cross-sectional analysis in a random sample of 2,270 individuals. We defined six body size phenotypes based on body mass index category (normal-weight, 18.5 to 24.9 kg/m2; overweight, 25 to 29.9 kg/m2; obese, ≥30.0 kg/m2) and the presence of ≤1 (metabolically healthy) or ≥2 (metabolically abnormal) cardiometabolic abnormalities: metabolically healthy normal-weight (MHNW), metabolically abnormal normal-weight (MANW), metabolically healthy overweight (MHOW), metabolically abnormal overweight (MAOW), metabolically healthy obese (MHO), and metabolically abnormal obese (MAO). We considered four cardiometabolic abnormalities: systolic and/or diastolic blood pressure ≥130/85 mm Hg, triglycerides ≥150 mg/dL, high-density-lipoprotein cholesterol levels <40/<50 mg/dL in men/women, and elevated glucose (fasting plasma glucose ≥100 mg/dL or previous diabetes). The prevalence of the MHO, MHOW, and MANW phenotypes was 2.2, 13.9, and 7.9%, respectively. Whereas 9.6% of obese and 32.6% of overweight individuals were metabolically healthy, 21.3% of the normal-weight subjects were metabolically abnormal. A multivariate regression model (adjusted for age, sex, and waist circumference) showed that age >40 years, male sex, and higher waist circumference were independently associated with the metabolically abnormal phenotype MANW, whereas younger age, female sex, and lower waist circumference were independently associated with the metabolically healthy phenotypes. The prevalence of MHO in our population is low and is more common in women and younger people. In contrast, a high proportion of normal-weight individuals (mainly over 40 years of age) in our population show cardiometabolic abnormalities.

Differences in insulin clearance between metabolically healthy and unhealthy obese subjects

Metabolically healthy obese (MHO) are relatively insulin sensitive and have a favorable cardio-metabolic risk profile compared with metabolically abnormal obese (MAO). To evaluate whether MAO individuals have a decreased insulin clearance compared with MHO individuals, 49 MHO, 147 MAO, and 172 non-obese individuals were analyzed in this cross-sectional study. Insulin clearance and insulin sensitivity were assessed through euglycemic hyperinsulinemic clamp. MHO subjects exhibited significant lower triglycerides, total cholesterol, 2-h post-challenge glucose, fasting and 2-h post-challenge insulin, steady-state plasma insulin, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase as compared with MAO individuals. Disposition index was higher in MHO subjects as compared with MAO individuals after adjusting for gender and age (P = 0.04). Insulin clearance was significantly lower in MAO individuals as compared with MHO and non-obese individuals. The difference between the two obese subgroups remained significant after adjusting for gender, age, waist circumference, fat mass, and insulin-stimulated glucose disposal (P = 0.03). The hepatic insulin extraction (C-peptide/insulin) in the fasting state was significantly higher in MHO subjects as compared with MAO individuals (P < 0.0001). In univariate analysis adjusted for gender and age, insulin clearance was correlated with hepatic insulin extraction (P = 0.01). In conclusion, insulin clearance differs among obese subjects with different metabolic phenotypes. Impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia observed in MAO individuals.

SAT0346 Metabolically Abnormal but Normal Weight, Metabolically Healthy Obesity, and Knee Osteoarthritis: A Cross-Sectional Study in Asian Women

BackgroundMetabolically abnormal but normal weight, also called metabolically obese normal weight, is a body phenotype that is not obese on the basis of height and weight, but is associated with...

Liver enzymes and vitamin D levels in metabolically healthy but obese individuals: Korean National Health and Nutrition Examination Survey

ObjectiveIncreased liver enzymes and decreased vitamin D levels are associated with insulin resistance and type 2 diabetes. We examined liver enzymes and vitamin D levels in metabolically healthy but obese (MHO) individuals and compared the values with those of other body size phenotypes in the Korean population. Materials/MethodsA total of 16,190 people over the age of 18years were analyzed using data from the Fourth Korean National Health and Nutrition Examination Survey, which is a nationally representative survey. Body size phenotypes were classified into four groups by body mass index (BMI) and number of metabolic syndrome components. ResultsThe prevalence of MHO was 14.9% in the entire population and 47.7% in the obese population. In a correlation analysis adjusted for age, sex, and BMI, AST and ALT levels were positively correlated with insulin resistance and cardiometabolic risk factors of the metabolic syndrome, whereas vitamin D level was negatively correlated with these variables. MHO individuals had significantly lower concentrations of AST and ALT compared to metabolically abnormal obese (MAO) subjects, although vitamin D levels were not significantly different. Furthermore, a multiple logistic regression analysis revealed that MHO individuals had lower risk of liver enzyme abnormality compared to MAO after adjusting for potential confounding factors. However, the risk of vitamin D deficiency was not significantly different among groups with different body size phenotypes. ConclusionsAlthough both liver enzymes and vitamin D levels are related to insulin resistance and metabolic syndrome, only liver enzymes were independently associated with MHO phenotype.

A Weight Loss Diet Intervention Has a Similar Beneficial Effect on Both Metabolically Abnormal Obese and Metabolically Healthy but Obese Premenopausal Women

Background/Aims: We studied the effect of a 12-week energy-restricted diet intervention on cardiometabolic risk in two groups of nonmorbid obese premenopausal Caucasian women, i.e. a metabolically abnormal obese (MAO) and a metabolically healthy but obese (MHO) group. Methods: The participants were 53 MAO and 25 MHO women (age range 19-49 years; body mass index inclusion criterion: 30-39.9). We assessed changes in body weight and composition, blood lipids, insulin resistance, hepatic enzymes, inflammatory markers and adipocytokines. Results: Overall, many of the study outcomes improved with the intervention in both MAO and MHO participants, but there was no difference in the magnitude of change between the groups. Body weight, waist circumference and total fat mass decreased significantly in response to the intervention in both MAO and MHO women (all p < 0.001). Fasting insulin, insulin resistance (homeostasis model assessment), hepatic enzymes (alanine aminotransferase and γ-glutamyltransferase), fatty liver index and leptin levels also decreased in both groups after the intervention (all p < 0.001), whereas total cholesterol, triglycerides and C-reactive protein decreased significantly only in MAO women (all p < 0.001). Conclusion: These findings reinforce the idea that MHO women would also benefit from a lifestyle weight reduction intervention.

Body Size Phenotypes and Low Muscle Mass: The Korean Sarcopenic Obesity Study (KSOS)

Unique subsets of body size phenotypes seem to be more prone or more resistant to the development of obesity-associated metabolic disorders, although the underlying mechanism is not yet clearly understood. We investigated the prevalence and risk of low muscle mass in subjects who are classified as either metabolically healthy normal weight (MHNW), metabolically abnormal but normal weight (MANW), metabolically healthy obese (MHO), or metabolically abnormal obese (MAO). Subjects were classified based on body mass index and presence of metabolic syndrome. Thigh muscle cross-sectional area was evaluated using computed tomography as an index of muscle mass in 492 apparently healthy adults enrolled in the Korean Sarcopenic Obesity Study (KSOS), an ongoing prospective observational cohort study. Low muscle mass was defined as thigh muscle cross-sectional area divided by weight (percent) of <1 SD below the mean values of young adults in both sexes. The prevalence rates of low muscle mass in MHNW, MANW, MHO, and MAO subjects were 6.2%, 17.8%, 23.2%, and 33.7%, respectively. In a multiple logistic regression analysis, men with the MANW phenotype showed a remarkably increased risk of low muscle mass (odds ratio = 11.30, 95% confidence interval, 1.73-73.28) compared with those with MHNW. Furthermore, in both men and women, MHO or MAO subjects had higher odds ratios of low muscle mass compared with MHNW subjects. The present study suggests that low muscle mass may be associated with different metabolic consequences according to body size phenotype.

Unacylated Ghrelin is associated with the isolated low HDL-cholesterol obese phenotype independently of insulin resistance and CRP level

BackgroundLow plasma high-density lipoprotein-cholesterol (HDL-c) level is commonly present in obesity and represents an independent cardiovascular risk factor. However, obese patients are a very heterogeneous population and the factors and mechanisms that contribute to low HDL-c remain unclear. The aim of this study was to investigate the association between plasma HDL-c levels and plasma hormonal profiles (insulin, adiponectin, resistin, leptin and ghrelin) in subsets of class II and III obese patients.MethodsFasting plasma levels of glucose, total cholesterol, LDL-c, HDL-c, triglycerides, free fatty acids, apoproteins A-I, B-100, B-48, C-II, C-III, insulin, hs-CRP, adipocytokines (adiponectin, resistin, leptin), unacylated ghrelin, body composition (DXA) and resting energy expenditure were measured in three subsets of obese patients: 17 metabolically abnormal obese (MAO) with metabolic syndrome and the typical metabolic dyslipidaemia, 21 metabolically healthy obese (MHO) without metabolic syndrome and with a normal lipid profile, and 21 isolated low HDL-c obese patients (LHO) without metabolic syndrome, compared to 21 healthy lean control subjects.ResultsInsulin resistance (HOMA-IR) increased gradually from MHO to LHO and from LHO to MAO patients (p < 0.05 between MHO and MAO and between LHO and MAO). In multiple regression analysis, serum unacylated ghrelin levels were only positively and independently associated with HDL-c levels in the LHO group (p = 0.032).ConclusionsThese results suggest that, in class II and III obese patients with an isolated low HDL-c phenotype, unacylated ghrelin is positively associated with HDL-c level independently of insulin resistance and CRP levels, and may contribute to the highly prevalent low HDL-c level seen in obesity.

Effects of Weight Loss Among Metabolically Healthy Obese Men and Women

OBJECTIVEWeight loss among metabolically healthy obese (MHO) individuals may be unnecessary or result in elevated cardio-metabolic risk. We studied the effects of exercise- or diet-induced weight loss on cardio-metabolic risk among MHO and metabolically abnormal obese (MAO) adults.RESEARCH DESIGN AND METHODSParticipants were 63 MHO and 43 MAO adults who took part in 3 to 6 months of exercise- or diet-induced weight loss intervention. Changes in anthropometry, adipose tissue distribution, and cardio-metabolic risk factors were assessed.RESULTSBody weight, waist circumference, and total abdominal and visceral adipose tissue were reduced in all subjects (P < 0.05). Improvements in insulin sensitivity were observed in MHO and MAO men and women (P < 0.05), but were greater in the MAO individuals (P < 0.05). Fasting insulin was the only other cardio-metabolic improvement among MHO individuals (P < 0.05).CONCLUSIONSLifestyle-induced weight loss among MHO subjects is associated with a reduction in total and abdominal obesity and improvement in selected cardio-metabolic risk factors.

Nutrition and Health

Objective: To determine whether fat free mass (FFM) is independently associated with the metabolically healthy obesity (MHO) phenotype, the metabolic syndrome (MS), and type 2 diabetes (T2D) in obese Asian adults.Methods: Obese patients (body mass index &lsqb;BMI] ≥25 kg/m2) seeking weight management at an academic medical center from 2007 to 2016 were included. FFM was measured by bioelectrical impedance.Results: Of the 552 patients (67.0% female, median age 40.5 years, median BMI 38.3 kg/m2), MHO was present in 19%, MS in 55.4%, and T2D in 32.6%. In multivariate models, higher fat-free mass index (FFMI) was independently associated with the metabolically abnormal obesity (MAO) phenotype, (odds ratio &lsqb;OR] 1.22, 95% confidence interval &lsqb;CI] 1.09–1.37), and increased risk of MS (OR 1.12, 95% CI 1.03–1.22) in women but not in men. Older age was independently associated with the MAO phenotype (OR 1.06, 95% CI 1.04–1.09 in women; OR 1.06, 95% CI 1.02–1.09 in men), MS (OR 1.05, 95% CI 1.03–1.06 in women; OR 1.05, 95% CI 1.02–1.07 in men), and T2D (OR 1.07, 95% CI 1.05–1.09 in women; OR 1.06, 95% CI 1.04–1.09 in men). Waist-hip ratio was independently associated with the MAO phenotype in men (OR 1.08, 95% CI 1.01–1.15), while waist circumference was associated with T2D in women (OR 1.03, 95% CI 1.01–1.05).Conclusion: Older age, central fat distribution, and—in contrast to previous findings—an increase in FFMI among women were independent predictors of adverse metabolic health in this cohort of middle-aged obese Asian adults. Further studies are required to elucidate underlying mechanisms and therapeutic implications of these findings.Abbreviations: BIA = bioelectrical impedance analysis BMI = body mass index CI = confidence interval DXA = dual-energy X-ray absorptiometry FFM = fat-free mass FFMI = fat-free mass index FM = fat mass HbA1c = glycated hemoglobin A1c MAO = metabolically abnormal obesity MHO = metabolically healthy obesity MS = metabolic syndrome OR = odds ratio T2D = type 2 diabetes WC = waist circumference WHR = waist-hip-ratio

Weight loss effect on inflammation and LDL oxidation in metabolically healthy but obese (MHO) individuals: low inflammation and LDL oxidation in MHO women

Recently, a subtype of obesity characterized as a metabolically healthy but obese (MHO) individual has been identified. However, limited data are available on these MHO individuals' metabolic and inflammatory profiles, and the effect of weight loss on these profiles. We investigated metabolic and inflammatory markers in MHO women to determine the effects of a 12-week weight loss on those markers. One hundred and twenty-nine overweight-obese Korean women participated for 12 weeks in a clinical intervention study involving a 300 kcal/day intake reduction. The subjects were divided into two groups: MHO and metabolically abnormal obese (MAO) individuals. Computed tomography was performed. C-reactive protein (CRP), interkeukin-6 (IL-6) and oxidized low-density lipoprotein (LDL), as well as blood lipids, glucose and insulin concentrations were determined at baseline and after weight loss. At baseline, plasma CRP (P<0.001), IL-6 (P<0.05) and oxidized LDL (P<0.001) levels were significantly lower in the MHO group than in the MAO group. Visceral fat at L1 (P<0.005) and visceral fat at L4 (P<0.001) were significantly lower in the MHO group than in the MAO group. The treatment induced weight loss averaging 3.11% of initial body weight, and the degree of weight loss between the two groups was similar. Visceral fat at L1 and L4 was reduced from its initial values by 3.2 and 5.4%, respectively, after weight loss. The levels of CRP (P<0.05) and oxidized LDL (P<0.01) were significantly reduced in the MAO group after the 12-week weight loss, whereas these effects were not seen in the MHO group. Our results showed that MHO individuals exhibited lower visceral fat accumulation and more favorable metabolic and inflammatory states than MAO individuals. After a 12-week weight loss program, significant reductions in blood lipids, CRP and oxidized LDL levels were observed in MAO individuals. However, there was no measurable effect of weight loss on lipid profiles and inflammation in MHO individuals, indicating differing effects of weight loss on these markers between MAO and MHO groups.

What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women?

Although obesity is often associated with insulin resistance and a cluster of metabolic disturbances, the existence of a subgroup of healthy but obese individuals has been postulated. It is unclear why some obese individuals fail to show traditional risk factors associated with the insulin resistance syndrome despite having a very high accumulation of body fat. To address this issue, we identified and studied a subgroup of metabolically normal but obese (MNO) postmenopausal women to gain insight into potential physiological factors that may protect them against the development of obesity-related comorbidities. We carefully examined the metabolic characteristics of 43 obese, sedentary postmenopausal women (mean +/- SD, 58.0 +/- 6.0 yr). Subjects were classified as MNO or as metabolically abnormal obese (MAO) based on an accepted cut-point for insulin sensitivity (measured by the hyperinsulinemic/euglycemic clamp technique). Thereafter, we determined 1) body composition (fat mass and lean body mass), 2) body fat distribution (abdominal visceral and sc adipose tissue areas, midthigh sc adipose tissue and muscle attenuation), 3) plasma lipid-lipoprotein levels, 4) plasma glucose and insulin concentrations, 5) resting blood pressure, 6) peak oxygen consumption, 7) physical activity energy expenditure, and 8) age-related onset of obesity with a questionnaire as potential modulators of differences in the risk profile. We identified 17 MNO subjects who displayed high insulin sensitivity (11.2 +/- 2.6 mg/min.kg lean body mass) and 26 MAO subjects with lower insulin sensitivity (5.7 +/- 1.1 mg/min.kg lean body mass). Despite comparable total body fatness between groups (45.2 +/- 5.3% vs. 44.8 +/- 6.6%; P: = NS), MNO individuals had 49% less visceral adipose tissue than MAO subjects (141 +/- 53 vs. 211 +/- 85 cm(2); P: < 0.01). No difference was noted between groups for abdominal sc adipose tissue (453 +/- 126 vs. 442 +/- 144 cm(2); P: = NS), total fat mass (38.1 +/- 10.6 vs. 40.0 +/- 11.8 kg), muscle attenuation (42.2 +/- 2.6 vs. 43.6 +/- 4.8 Houndsfield units), and physical activity energy expenditure (1060 +/- 323 vs. 1045 +/- 331 Cal/day). MNO subjects had lower fasting plasma glucose and insulin concentrations and lower insulin levels during the oral glucose tolerance test (P: values ranging between 0.01-0.001). No difference was observed between groups for 2-h glucose levels and glucose area during the oral glucose tolerance test. MNO subjects showed lower plasma triglycerides and higher high density lipoprotein cholesterol concentrations than MAO individuals (P: < 0.01 in both cases). Results from the questionnaire indicated that 48% of the MNO women presented an early onset of obesity (<20 yr old) compared with 29% of the MAO subjects (P: = 0.09). Stepwise regression analysis showed that visceral adipose tissue and the age-related onset of obesity explained 22% and 13%, respectively, of the variance observed in insulin sensitivity (total r(2) = 0.35; P: < 0.05 in both cases). Our results support the existence of a subgroup of obese but metabolically normal postmenopausal women who display high levels of insulin sensitivity despite having a high accumulation of body fat. This metabolically normal profile is associated with a lower accumulation of visceral adipose tissue and an earlier age-related onset of obesity.