Metabolically Healthy Overweight/obese Research Articles

Abstract 4772: Metabolic phenotype, age acceleration, and obesity-related cancer risk in Women's Health Initiative and Atherosclerosis Risk in Communities cohorts

Abstract Introduction: While normal physiologic aging causes metabolic decline, metabolic dysregulation owing to excess nutrient intake, physical inactivity, and obesity may drive accelerated aging. However, the relationship of accelerated aging with metabolic dysfunction across different levels of BMI (i.e., metabolic obesity phenotype) and whether it may mediate the relationship with obesity-related cancer (ORC) risk is not well established. Methods: To test this hypothesis, we are leveraging existing blood-based DNA methylation (DNAm) data within the Women’s Health Initiative (WHI) and the Atherosclerosis Risk in Communities (ARIC) cohorts. Weight, height and blood pressure were measured by trained technicians in the respective cohorts and fasting blood glucose, triglycerides and HDL cholesterol were quatified by standard clinican assays. Metabolic obesity phenotypes are classified as metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obese (MHO), and metabolically unhealthy overweight/obese (MUO) when defined by ATP III criteria. Age acceleration was measured as a residual from regressing pan-tissue Horvath’s DNAmAge on chronological age. Results: The mean baseline age was 64 ± 6.6 years and 54 ± 5.7 year among WHI and ARIC participants, respectively and the age acceleration was measured at an mean follow-up time of 16 years from baseline for WHI and 3.5 years from baseline for ARIC cohort. The outcome of interest, ORC incidence was observed among 474 participants of which 387 were women. The median time for cancer diagnosis from baseline was 25 year and from DNAm measurement was 18.6 years. Of the 4341 (70% women) participants included in the analysis, 23.9% were MHNW, 3.2% MUNW, 39% MHO, and 33.5% MUO. A 31.5% of MHNW, 40.4% of MUNW, 28.7% of MHO, and 35.2% of MUO showed age acceleration. MUNW (OR 1.47, 95% CI: 1.03-2.11) and MUO (OR 1.18, 95% CI: 1.00-1.40) individuals at baseline had increased odds of experiencing age acceleration at a follow-up visit. The risk of all ORC combined was significantly elevated among MUO (HR 1.63, 95% CI: 1.27-2.09) compared to MHNW. Age acceleration at the follow-up visit was not significantly associated with ORC risk (HR 0.91, 95% CI: 0.75-1.11). These analyses were not adjusted for confounders. Conclusions: MUNW and MUO individuals had increased odds of age acceleration at a follow-up visit. Furthermore, MUO individuals were at an elevated risk of ORC, compared to individuals with MHNW. Accelerated aging does not appear to mediate this association, as accelerated aging was not associated with ORC. Citation Format: Prasoona Karra, Garnet L. Anderson, Mary C. Playdon, Sheetal Hardikar, Aladdin Shadyab, Kari E. North, Anne E. Justice, Elizabeth A. Platz, Jan Bressler, Anna Prizment, Weihua Guan, Dominique S. Michaud, Eric A. Whitsel, Brock C. Christensen, Lucas A. Salas. Metabolic phenotype, age acceleration, and obesity-related cancer risk in Women's Health Initiative and Atherosclerosis Risk in Communities cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4772.

Metabolic obesity phenotypes and obesity-related cancer risk in the National Health and Nutrition Examination Survey.

Body mass index (BMI) fails to identify up to one-third of normal weight individuals with metabolic dysfunction who may be at increased risk of obesity-related cancer (ORC). Metabolic obesity phenotypes, an alternate metric to assess metabolic dysfunction with or without obesity, were evaluated for association with ORC risk. National Health and Nutrition Examination Survey participants from 1999 to 2018 (N = 19,500) were categorized into phenotypes according to the metabolic syndrome (MetS) criteria and BMI: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obese (MHO) and metabolically unhealthy overweight/obese (MUO). Adjusted multivariable logistic regression models were used to evaluate associations with ORC. With metabolic dysfunction defined as ≥1 MetS criteria, ORC cases (n = 528) had higher proportions of MUNW (28.2% vs. 17.4%) and MUO (62.6% vs. 60.9%) phenotypes than cancer-free individuals (n = 18,972). Compared with MHNW participants, MUNW participants had a 2.2-times higher ORC risk [OR (95%CI) = 2.21 (1.27-3.85)]. MHO and MUO participants demonstrated a 43% and 56% increased ORC risk, respectively, compared to MHNW, but these did not reach statistical significance [OR (95% CI) = 1.43 (0.46-4.42), 1.56 (0.91-2.67), respectively]. Hyperglycaemia, hypertension and central obesity were all independently associated with higher ORC risk compared to MHNW. MUNW participants have a higher risk of ORC than other abnormal phenotypes, compared with MHNW participants. Incorporating metabolic health measures in addition to assessing BMI may improve ORC risk stratification. Further research on the relationship between metabolic dysfunction and ORC is warranted.

Obesity Metabolic Phenotype, Changes in Time and Risk of Diabetes Mellitus in an Observational Prospective Study on General Population.

Objectives: To evaluate the distribution and changes in different obesity metabolic phenotypes, as well as their impact on the incidence of type 2 diabetes mellitus (T2DM) in a northwest Chinese population sample. Methods: Data comes from prospective cohort study (n = 1,393, mean follow up = 9.46 years). Participants were classified into four groups through a combination of the Chinese Diabetes Society (CDS) diagnostic criteria for metabolic syndrome with anthropometric measurements: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO). Cox regression models with time-dependent covariates were used to evaluate changes in obesity metabolic phenotypes and risk of T2DM. Results: Participants in MUO state had the highest risk of developing T2DM, the incidence density was 12.10/1,000 person-year. The MHO and MUO groups showed an increased risk of incident diabetes based on body mass index (BMI) (HR, 1.29; 95% CI, 1.03–1.61; p = 0.026 and HR, 1.20; 95% CI, 1.02–1.40; p = 0.024 respectively.) Besides, the MHO group had an increased risk of incident diabetes based on waist circumference (WC) (HR, 1.41; 95% CI, 1.10–1.80; p = 0.006). Conclusion: Diabetes is more frequent in the MHO and MUO groups and co-occurrence of obesity and metabolic abnormalities (MA) contributes to the development of T2DM.

The Association Between Hyperuricemia and Obesity Metabolic Phenotypes in Chinese General Population: A Retrospective Analysis.

PurposeSerum uric acid (UA) not only affects the development of obesity but also alters the metabolic status in obese subjects; thus we investigated the relationship between serum UA and the overweight/obese metabolic phenotypes.MethodsThe demographic, biochemical, and hematological data were collected for 12,876 patients undergoing routine physical examination, and 6,912 participants were enrolled in our study. Participants were classified into four obesity metabolic phenotypes according to their BMI and the presence of metabolic syndrome: metabolically healthy overweight/obese (MHOO), metabolically healthy and normal weighted (MHNW), metabolically abnormal and overweight/obese (MAOO), and metabolically abnormal but normal weighted (MANW). Univariate and multivariate logistic regression analysis, stratified analysis, and also interaction analysis were conducted to analyze the relationship between serum UA and obesity metabolic phenotypes.ResultsMultivariable logistic regression analysis showed that hyperuricemia was positively associated with MHOO, MANW, and MAOO phenotypes relative to MHNW. After adjusting for the confounding factors, the odds ratios (OR) for individuals with hyperuricemia to be MHOO, MANW, and MAOO phenotypes were 1.86 (1.42–2.45), 2.30 (1.44–3.66), and 3.15 (2.34–4.24), respectively. The ORs for having MHOO, MANW, and MAOO increased 6% [OR: 1.06 (1.05–1.07), P < 0.0001], 5% [OR: 1.05 (1.03–1.07), P < 0.0001], and 11% [OR: 1.11 (1.10–1.13), P < 0.0001] for each 10 unit (μmol/L) of increase in serum UA level. Stratification analysis as well as an interaction test showed that sex and age did not interfere with the association of hyperuricemia with each metabolic phenotype. In terms of the components of the metabolic syndrome, after adjusting for other confounding factors including all of the metabolic indicators except itself, hyperuricemia was positively associated with increased BMI [OR: 1.66 (1.32–2.09), P < 0.0001], hypertriglyceridemia [OR: 1.56 (1.21–2.02), P = 0.0006], and hypertension [OR: 1.22 (1.03–1.46), P = 0.0233], while it had no significant association with hyperglycemia and low HDL-C (all P > 0.05).ConclusionIn our study, we discovered that hyperuricemia was positively associated with MHOO, MANW, and MAOO phenotypes, and this relationship was independent of sex and age.

Wrist circumference as a novel predictor of transition from metabolically healthy to unhealthy phenotype in overweight/obese adults: a gender-stratified 15.5-year follow-up

BackgroundIndividuals with transition from metabolically healthy overweight/obese (MHO) to metabolically unhealthy overweight/obese (MUO) phenotype are significantly predisposed to greater risks of cardiovascular events compared to those with a persistent MHO phenotype. The aim of this study was to evaluate the predictive performance of wrist circumference for this transition in adults over a 15.5-year follow-up.MethodsWe included 309 males and 821 females with the age of ≥18 years old, body mass index ≥25 kg/m2, and metabolically healthy status according to the criteria of the Joint Interim Statement. The incidence of MUO phenotype was evaluated for each gender, across tertiles wrist circumference, using Cox-proportional hazard models.ResultsThe overall rate of transition from MHO to MUO phenotype was 87.1% in males and 77.5% in females. The hazard ratios (HRs) with 95% CI across second and third tertiles of wrist circumference were 0.89 (0.64-1.24) and 1.31 (0.99-1.73) in men (P for trend =0.027); and 1.34 (1.09-1.66) and 1.61 (1.30-2.00) in women (P for trend <0.001), respectively. After multivariable adjustment, HRs across second and third tertiles of wrist circumference were 0.92 (0.64-1.32) and 1.18 (0.83-1.67) in males (p for trend =0.352), and 1.32 (1.05-1.65) and 1.34 (1.06-1.96) in females (p for trend =0.025), respectively.ConclusionsWrist circumference significantly predicts the transition from MHO to MUO phenotype in adults of both genders. However, it is an independent predictor of the transition only in females. Future studies are warranted to clarify the role of wrist circumference mechanisms on metabolic risk deterioration.

Contribution of 20-year body mass index and waist circumference history to poor cardiometabolic health in overweight/obese and normal weight adults: A cohort study

Background and aimsWe investigated the associations of 20-year body mass index (BMI) and waist circumference (WC) histories with risk of being 1) metabolically unhealthy overweight/obese (MUOO) vs metabolically healthy overweight/obese (MHOO) and 2) metabolically unhealthy normal weight (MUNW) vs metabolically healthy normal weight (MHNW). Methods and resultsParticipants comprised 3018 adults (2280 males; 738 females) with BMI and WC measured, every ~5 years, in 1991–1994, 1997–1999, 2002–2004, 2007–2009, and 2012–2013. Mean age in 2012–2013 was 69.3 years, with a range of 59.7–82.2 years. Duration was defined as the number of times a person was overweight/obese (or centrally obese) across the 5 visits, severity as each person's mean BMI (or WC), and variability as the within-person standard deviation of BMI (or WC). At the 2013–2013 visit, participants were categorised based on their weight (overweight/obese or normal weight; body mass index (BMI) ≥25 kg/m2) and health status (healthy or unhealthy; two or more of hypertension, low high-density lipoprotein cholesterol, high triglycerides, high glucose, and high homeostatic model assessment of insulin resistance). Logistic regression was used to estimate associations with the risk of being MUNW (reference MHNW) and MUOO (reference MHOO) at the last visit. BMI and WC severity were each related to increased risk of being unhealthy, with estimates being stronger among normal weight than overweight/obese adults. The estimates for variability exposures became null upon adjustment for severity. Individuals who were overweight/obese at all 5 time points had a 1.60 (0.96–2.67) times higher risk of being MUOO than MHOO compared to those who were only overweight/obese at one (i.e., the last) time point. The corresponding estimate for central obesity was 4.20 (2.88–6.12). Greater duration was also related to higher risk of MUNW than MHNW. ConclusionBeing overweight/obese yet healthy seems to be partially attributable to lower exposure to adiposity across 20 years of adulthood. The results highlight the importance of maintaining optimum and stable BMI and WC, both in adults who become and do not become overweight/obese.

Metabolomic Signature Between Metabolically Healthy Overweight/Obese and Metabolically Unhealthy Overweight/Obese: A Systematic Review.

The clinical manifestations of overweight/obesity are heterogeneous and complex. In contrast to metabolically unhealthy overweight/obese (MUO), a particular sub-group of obese patients who are considered as metabolically healthy overweight/obese (MHO), display favorable metabolic profiles characterized by high levels of insulin sensitivity, normal blood pressure, as well as favorable lipid, inflammation, hormone, liver enzyme, and immune profiles. While only a few available studies focused on the metabolic files underlying the obese phenotypes, the current review aimed to perform a systematic review of available studies focusing on describing the metabolomic signature between MUO and MHO. We did the systematic search for literature on MEDLINE (PubMed), the Cochrane Library, EMBASE, and searched for the references of relevant manuscripts from inception to 29 May 2020. After critical selection, 20 studies were eligible for this systematic review and evaluated by using QUADOMICS for quality assessment. Eventually, 12 of 20 studies were classified as “high quality”. Branched-chain amino acids (isoleucine, leucine, and valine), aromatic amino acids (phenylalanine and tyrosine), lipids (palmitic acid, palmitoleic acid, oleic acid, eicosapentaenoic acid, and docosahexaenoic acid), and acylcarnitines (propionyl carnitine) levels might be elevated in MUO. The current results suggested that MHO showed a favorable trend in the overall metabolic signature. More longitudinal studies are needed to elaborate deeply on the metabolic pathway and the relationship between metabolic patterns and the occurrence of the disease.

Deciphering Biochemical and Molecular Signatures Associated with Obesity in Context of Metabolic Health.

This study aims to identify the clinical and genetic markers related to the two uncommon nutritional statuses—metabolically unhealthy normal-weight (MUNW) and metabolically healthy overweight/obese (MHOW) individuals in the physically active individuals. Physically active male volunteers (n = 120) were recruited, and plasma samples were analyzed for the clinical parameters. Triglycerides, HDL-Cholesterol, LDL-cholesterol, total cholesterol, C-reactive protein, and insulin resistance were considered as markers of metabolic syndrome. The subjects were classified as ‘healthy’ (0 metabolic abnormalities) or ‘unhealthy’ (≥1 metabolic abnormalities) in their respective BMI group with a cut-off at 24.9 kg/m2. Analysis of biochemical variables was done using enzyme linked immunosorbent assay (ELISA) kits with further confirmation using western blot analysis. The microarray was conducted, followed by quantitative real-time PCR to identify and analyze differentially expressed genes (DEGs). The MHOW group constituted 12.6%, while the MUNW group constituted 32.4% of the total study population. Pro-inflammatory markers like interleukin-6, tumor necrosis factor (TNF)-α, and ferritin were increased in metabolically unhealthy groups in comparison to metabolically healthy groups. Gene expression profiling of MUNW and MHOW individuals resulted in differential expression of 7470 and 5864 genes, respectively. The gene ontology (GO) biological pathway analysis showed significant enrichment of the ‘JAK/STAT signaling pathway’ in MUNW and ‘The information-processing pathway at the IFN-β enhancer′ pathway in MHOW. The G6PC3 gene has genetically emerged as a new distinct gene showing its involvement in insulin resistance. Biochemical, as well as genetic analysis, revealed that MUNW and MHOW are the transition state between healthy and obese individuals with simply having fewer metabolic abnormalities. Moreover, it is possible that the state of obesity is a biological adaptation to cope up with the unhealthy parameters.

Circulating levels of IL-33 are elevated by obesity and positively correlated with metabolic disorders in Chinese adults

BackgroundInterleukin-33 (IL-33) plays a pivotal role in regulating innate immune response and metabolic homeostasis. However, whether its circulating level is correlated with obesity and metabolic disorders in humans remains largely unknown. We aimed to address this gap by determining IL-33 serum level and its downstream type 2 inflammatory cytokines interleukin-5 (IL-5) and interleukin-13 (IL-13) in overweight/obese population, and analyzing the specific associations between IL-33 and obesity metabolic phenotypes.Methods217 subjects were enrolled and divided into three groups: healthy control (HC) subjects, metabolically healthy overweight/obese (MHOO) subjects and metabolically unhealthy overweight/obese (MUOO) subjects. Circulating levels of IL-33, IL-5 and IL-13 were measured using ELISA analyses. Multivariate regression analyses were further performed to determine the independent association between IL-33 and obesity metabolic phenotypes.ResultsCirculating levels of IL-33 were significantly elevated in subjects of MUOO group compared with HC group and MHOO group, while no significant difference was observed between the latter two groups in IL-33 levels. Consistent with this, serum levels of IL-5/13 were higher in the MUOO group compared with HC and MHOO groups. After adjusted for all confounders, MUOO phenotype was significantly associated with increased IL-33 serum levels (OR = 1.70; 95% CI 1.09–2.64; p = 0.019). With the MHOO group as the reference population, higher circulating level of IL-33 was also positively associated with MUOO phenotype after adjusting for confounders (OR = 1.50; 95% CI 1.20–1.88; p = 2.91E−4). However, there was no significant association between MHOO phenotype and IL-33 levels (p = 0.942). Trend analysis further confirmed the positive correlation between MUOO phenotype and IL-33 level (p for trend = 0.019). Additionally, IL-33 was significantly and positively correlated with diastolic blood pressure (DBP), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cell (WBC), neutrophil and IL-5 only in MUOO group, while inversely correlated with high density lipoprotein cholesterol (HDL-C) in MHOO subjects.ConclusionCirculating levels of IL-33 were significantly elevated in overweight/obese Chinese adults with metabolic disorders. Increased levels of IL-33 were positively associated with metabolically unhealthy overweight/obese phenotype and several metabolic syndrome risk factors.

Association of Metabolic Obesity Phenotypes and Total Testosterone in Chinese Male Population.

ObjectiveObesity and metabolic syndrome have been reported to exert an impact on the male reproductive system with decreasing levels of serum total testosterone (TT); however, the effect of different metabolic obesity phenotypes on testosterone has been poorly studied. We aimed to evaluate the association of metabolic obesity phenotypes and total testosterone levels in a Chinese male population.MethodsWe performed a retrospective study based on an epidemiological investigation, a total of 4,081 male individuals aged from 40–75 years old were recruited. The population was classified as metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO) according to normal weight (BMI<25.0) and overweight/obesity (BMI≥25.0) with or without metabolic syndrome.ResultsWe collected 563 hypotestosteronemia among 4,081 male individuals. The odds ratios (ORs) (95% CIs) of hypotestosteronemia in obesity and metabolic syndrome were 3.072 (2.414–3.911) and 3.294 (2.631–4.125), respectively, after adjusting for age, luteinizing hormone, smoking status, and alcohol consumption. Compared to the MHNW group, male subjects in MHO, MUNW, and MUO groups had decreased serum TT levels. Additionally, the MUO group had a lowest concentration of serum TT and a highest proportion of hypotestosteronemia. There was no significant difference of TT levels between the MHO and MUNW groups.ConclusionObesity and metabolic syndrome are independent risk factors of hypotestosteronemia in Chinese male populations. Our study also suggested that individuals with MHO, MUNW, and MUO have a higher risk of developing hypotestosteronemia.

The association between transition from metabolically healthy obesity to metabolic syndrome, and incidence of cardiovascular disease: Tehran lipid and glucose study.

Considering that the data available on the cardiovascular (CV) risk of metabolically healthy obesity phenotype, and the effect of transition to an unhealthy status are inconsistent, the aim of this study was to investigate the possible role of transition to unhealthy status among metabolically healthy overweight/obese (MHO) subjects on CVD incidence over a median follow-up of 15.9 years. In this large population-based cohort, 6758 participants (41.6% men) aged ≥ 20 years, were enrolled. Participants were divided into 4 groups based on their obesity phenotypes and follow-up results, including persistent metabolically healthy normal weight (MHNW), persistent MHO, transitional MHO and metabolically unhealthy overweight/obese (MUO). Metabolic health was defined as not having metabolic syndrome based on the Joint Interim Statement (JIS) criteria. Multivariable adjusted hazard ratios (HRs) were calculated for cardiovascular events. During follow-up, rate of CVD Incidence per 1000 person-years were 12 and 7 in males and females, respectively. Multivariable adjusted HRs (CI 95%) of CVD incidence among males and females were 1.37 (.78-2.41) and .85 (.34-2.15) in persistent MHO group, 1.55 (1.02-2.37) and .93 (.41-2.12) in transitional MHO group and 2.64 (1.89-3.70) and 2.65 (1.24-5.68) in MUO group. Our findings showed that CVD risk did not increase in the persistent MHO phenotype over a 15.9-year follow-up in both sexes. However, transition from MHO to MUO status during follow-up increased the CVD risk just in male individuals. Further studies are needed to provide conclusive evidence in favor of benign nature of transitional MHO phenotype in females.

Effect of Sarcopenia and Body Shape on Cardiovascular Disease According to Obesity Phenotypes.

BackgroundThis study aimed to assess the effects of sarcopenia and A Body Shape Index (ABSI) on cardiovascular disease (CVD) risk according to obesity phenotypes.MethodsWe used data from the National Health and Nutrition Examination Survey 1999 to 2012. A total of 25,270 adults were included and classified into the following groups: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO). Sarcopenia was defined as the appendicular skeletal mass index <7 kg/m2 in men and <5.5kg/m2 in women. A multivariate logistic regression analysis was performed to evaluate the odds ratio (OR) of sarcopenia and ABSI for CVD events according to the obesity phenotype.ResultsThe MHNW participants with sarcopenia had higher risk for CVD than those without sarcopenia (OR, 2.69; 95% confidence interval [CI], 1.56 to 4.64). In the analysis with MHNW participants without sarcopenia as a reference, the participants with sarcopenia showed a higher OR for CVD than those without sarcopenia in both MHO (OR in participants without sarcopenia, 3.31; 95% CI, 1.94 to 5.64) (OR in participants with sarcopenia, 8.59; 95% CI, 2.63 to 28.04) and MUO participants (OR in participants without sarcopenia, 5.11; 95% CI, 3.21 to 8.15) (OR in participants with sarcopenia, 8.12; 95% CI, 4.04 to 16.32). Participants within the second and third tertiles of ABSI had higher ORs for CVDs than the counterpart of obesity phenotypes within the first tertile.ConclusionThese results suggest that clinical approaches that consider muscle and body shape are required.

Incidence of diabetes according to metabolically healthy or unhealthy normal weight or overweight/obesity in postmenopausal women: the Women's Health Initiative.

To determine the relationship of metabolic weight categories with incident diabetes mellitus (DM) in postmenopausal women. The Women's Health Initiative (WHI) enrolled 161,808 postmenopausal women aged 50 to 79 years. We included those with cardiovascular disease (CVD) biomarkers and free of CVD and prevalent DM (n = 17,043) at baseline. Normal weight was defined as a body mass index (BMI) ≥18.5 and <25 kg/m, and waist circumference (WC) <88 cm and overweight/obesity as a BMI ≥25 kg/m or WC ≥88 cm. Metabolically healthy was based on <2 and metabolically unhealthy ≥2 traits of the following: triglycerides ≥150 mg/dL, systolic blood pressure (BP) ≥130 mm Hg or diastolic BP ≥85 mm Hg, or antihypertensives or diuretics, fasting glucose ≥100 mg/dL or DM medication, and high-density lipoprotein cholesterol <50 mg/dL. Cox regression was performed to determine the risk of incident DM among metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUHNW), metabolically healthy overweight/obese (MHO), and metabolically unhealthy overweight/obese (MUHO). Among our sample, 2,253 (13.3%) participants developed DM over a mean ± standard deviation follow-up time of 15.6 ± 3.4 years. Compared with MHNW (n = 162 incident DM cases), an increased risk of incident DM was observed in MUHNW (n = 102 cases) (hazard ratio [HR] 2.24, 95% confidence interval [CI] 1.74-2.88, P < 0.0001), MHO (n = 624 cases) (HR 1.68, 95% CI 1.40-2.00, P < 0.0001), and MUHO (n = 1,365 cases) (HR 4.51, 95% CI 3.82-5.35, P < 0.0001). Among postmenopausal women, MUHNW and MHO confer an approximate doubling in the risk and MUHO more than a four-fold increased risk for developing DM.

Sociodemographic and metabolic risk characteristics associated with metabolic weight categories in the Women's Health Initiative.

The Women's Health Initiative enrolled 161 808 postmenopausal women ages 50-79. We included those free of cardiovascular disease (CVD) and with CVD risk factors and biomarkers (n = 19 412). Normal weight was defined as a BMI ≥18.5 and <25 kg/m2 and waist circumference <88 cm and overweight/obesity as a BMI ≥25 kg/m2 or waist circumference ≥88 cm. Metabolically healthy was based on <2 and metabolically unhealthy ≥2 traits: triglycerides ≥150 mg/dl, systolic blood pressure (BP) ≥130 mmHg or diastolic BP ≥85 mmHg or antihypertensives or diuretics, fasting glucose ≥100 mg/dl or diabetes medication, and high-density lipoprotein cholesterol <50 mg/dl. Polytomous multinomial logistic regression with generalized link logit function provided the odds of metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUHNW), metabolically healthy overweight/obese (MHO), and metabolically unhealthy overweight/obese (MUHO) according to demographic and risk factor measures. Among the 19 412 postmenopausal women, 2369 (12.2%) participants had prevalent diabetes. Advanced age was associated with an increased odds of MUHNW as compared with the MHNW after adjusting for covariates [odds ratio (OR) 1.04, P < 0.0001]. Black/African American ethnicity was associated with a decreased odds of MUHNW (OR 0.64, P < 0.0001) and MUHO (OR 0.77, P = 0.0004), while an increased odds for MHO (OR 1.50, P < 0.0001) as compared with White MHNW. Advanced age and ethnicity are important indicators of metabolic weight categories among postmenopausal women.

Differences in Brain Volume between Metabolically Healthy and Unhealthy Overweight and Obese Children: The Role of Fitness.

The aim of this study was to examine whether metabolically healthy overweight/obese children have greater global and regional gray matter volumes than their metabolically unhealthy peers. We further examined the association between gray matter volume and academic achievement, along with the role of cardiorespiratory fitness in these associations. A total of 97 overweight/obese children (10.0 ± 1.2 years) participated. We classified children as metabolically healthy/unhealthy based on metabolic syndrome cut-offs. Global and regional brain volumes were assessed by magnetic resonance imaging. Academic achievement was assessed using the Woodcock-Muñoz standardized test. Cardiorespiratory fitness was assessed by the 20 m shuttle run test. Metabolically healthy overweight/obese (MHO) children had greater regional gray matter volume compared to those who were metabolically unhealthy (MUO) (all p ≤ 0.001). A similar trend was observed for global gray matter volume (p = 0.06). Global gray matter volume was positively related to academic achievement (β = 0.237, p = 0.036). However, all the associations were attenuated or disappeared after adjusting for cardiorespiratory fitness (p > 0.05). The findings of the present study support that metabolically healthy overweight/obese children have greater gray matter volume compared to those that are metabolically unhealthy, which is in turn related to better academic achievement. However, cardiorespiratory fitness seems to explain, at least partially, these findings.

A Metabolically Healthy Profile Is a Transient Stage When Exercise and Diet Are Not Supervised: Long-Term Effects in the EXERDIET-HTA Study.

Metabolically unhealthy obesity (MUO) is a regular state in people with primary hypertension (HTN), obesity, and who are physically inactive. To achieve and maintain a metabolically healthy overweight/obese (MHO) state should be a main treatment goal. The aims of the study were (1) to determine differences in metabolic profiles of overweight/obese, physically inactive individuals with HTN following a 16-week (POST) supervised aerobic exercise training (SupExT) intervention with an attentional control (AC) group, and (2) to determine whether the changes observed were maintained following six months (6 M) of unsupervised time. Participants (n = 219) were randomly assigned into AC or SupExT groups. All participants underwent a hypocaloric diet. At POST, all participants received diet and physical activity advice for the following 6 M, with no supervision. All measurements were assessed pre-intervention (PRE), POST, and after 6 M. From PRE to POST, MUO participants became MHO with improved (p < 0.05) total cholesterol (TC, ∆ = −12.1 mg/dL), alanine aminotransferase (∆ = −8.3 U/L), glucose (∆ = −5.5 mg/dL), C-reactive protein (∆ = −1.4 mg/dL), systolic blood pressure (SBP), and cardiorespiratory fitness (CRF) compared to unhealthy optimal cut-off values. However, after 6 M, TC, glucose, and SBP returned to unhealthy values (p < 0.05). In a non-physically active population with obesity and HTN, a 16-week SupExT and diet intervention significantly improves cardiometabolic profile from MUO to MHO. However, after 6 M of no supervision, participants returned to MUO. The findings of this study highlight the need for regular, systematic, and supervised diet and exercise programs to avoid subsequent declines in cardiometabolic health.

Abstract P285: Sociodemographic and Metabolic Risk Characteristics Associated with Metabolic Weight Categories in the Women's Health Initiative

Introduction: To identify sociodemographic and metabolic correlates of weight categories in postmenopausal women. Hypothesis: We assessed the hypothesis that postmenopausal women with metabolically unhealthy normal weight (MUHNW), metabolically healthy overweight/obese (MHO), and metabolically unhealthy overweight/obese (MUHO) were more likely to have adverse risk factors as compared to those with metabolically healthy normal weight (MHNW). Methods: The Women’s Health Initiative (WHI) enrolled 161,808 postmenopausal women ages 50-79. We included those free of cardiovascular disease (CVD) and with CVD risk factors and biomarkers (n=19,412). Normal weight was defined as a body-mass index (BMI) ≥18.5 and &lt;25 kg/m 2 and waist circumference (WC) &lt;88 cm and overweight/obesity as a BMI &gt; 25 kg/m 2 or WC &gt; 88 cm. Metabolically healthy was based on &lt;2 and metabolically unhealthy &gt; 2 traits: triglycerides &gt; 150 mg/dl, systolic blood pressure (BP) &gt; 130 mmHg or diastolic BP &gt; 85 mmHg or antihypertensives or diuretics, fasting glucose &gt; 100 mg/dl or diabetes medication, and HDL-cholesterol &lt;50 mg/dl. Multinomial logistic regression with generalized link logit function provided the odds ratio (ORs) of MHNW, MUHNW, MHO and MUHO. Results: The table shows the ORs of risk factors and biomarkers. Among the 19,412 participants, 2,369 (12.2%) had prevalent diabetes and a mean age of 63.3 ± 0.05 (SEM). Advanced age was associated with a greater odds of MUHNW and a lower odds of MHO as compared to the MHNW after adjusting for covariates. African-Americans were associated with a decreased likelihood of MUHNW and MUHO, while Hispanics were associated with a decreased likelihood of MHO and MUHO as compared to MHNW. Low-income had a greater odds of MUHNW, yet high-income had a lower odds of MHO or MUHO. Total cholesterol, insulin and C-reactive protein were associated with a greater odds of MUHNW, MUHO or MHO. Conclusions: Advanced age, ethnicity, income and biomarkers are important indicators of metabolic weight categories among postmenopausal women.

Association Between a Comprehensive Movement Assessment and Metabolically Healthy Overweight Obese Adults

Physical activity (PA) and sedentary behavior are associated with metabolic health in overweight and obese individuals. However, the role of comprehensive health-related movement guidelines on PA, recreational screen time, and sleep among Metabolically Healthy Overweight-Obese (MHO) individuals is unknown. We investigated differences in comprehensive movement assessment scores between adults classified as MHO or Non-MHO. The sample included 513 adults (46.2% male), aged 19 to 85 years, body mass index (BMI) ≥ 25, from cycle 2005–2006 of the National Health and Nutrition Examination Survey. Comprehensive movement assessment outcomes were defined as meeting modified 24-Hour Movement Guidelines criteria, with thresholds adapted for adults. 13.8% of participants were MHO (normal serum glucose, triglycerides, HDL-cholesterol, and systolic and diastolic blood pressure). Only 1.4% of MHO participants met all guidelines. MHO and Non-MHO participants had similar comprehensive movement assessment scores (MHO: 18.3% vs. Non-MHO: 10.9%; p = 0.072). MHO individuals had less continuous recreational screen time than Non-MHO individuals (1.8 ± 1.4 hrs/day vs. 2.5 ± 1.6 hrs/day; p < 0.001). Meeting the recreational screen time recommendation was the only variable associated with the MHO phenotype (OR:4.84 95%CI: 2.33–10.07). This association remained after adjusting for age, sex, ethnicity, education, and BMI (OR: 3.53 95%CI: 1.72–7.24). Our results suggest the importance of limiting recreational screen time in adults to optimize cardiometabolic risk profile in individuals living with overweight or obesity. Using movement guidelines with a screen time component to assess the risk associated with health outcomes in adults appears to provide a better assessment.

Metabolically healthy obesity reduces the risk of Alzheimer's disease in elders: a longitudinal study.

A subgroup of overweight/obese individuals, who had favorable metabolic profiles, was termed as metabolically healthy overweight/obese (MHO). Several studies suggested that MHO individuals were not at increased risk of cardiovascular disease and all-course mortality. However, whether MHO is associated with excess risk of Alzheimer’s disease (AD) in elders remains unclear. To explore the risk of AD among MHO phenotype and investigate whether MHO associates with neurodegenerative biomarkers of AD, we assessed body mass index-metabolic status phenotypes of 1199 longitudinal elders from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort using the Adult Treatment Panel-III (ATP- III) criteria. MHO subjects were at a significantly decreased risk for AD (adjusted HR=0.73, 95% CI: 0.54-0.97) compared with metabolically healthy normal weight (MHNW) subjects. In multivariable linear regression models, the cross-sectional associations of MHO with cerebrospinal fluid (CSF) biomarkers, brain Aβ load, and cortical structure were explored. MHO was positively correlated with CSF-Aβ (β=0.746, P=0.015), hippocampal volume (β=0.181, P=0.011), and whole brain volume (β=0.133, P=0.004). The MHO phenotype of the elder conferred a decreased risk of AD and its role may be driven by Aβ.

Comparison of dietary and plasma phospholipid fatty acids between normal weight and overweight black South Africans according to metabolic health: The PURE study

BackgroundInformation regarding circulating fatty acids (FA) in association with metabolic health in black Africans is scarce, while the usefulness of circulating FAs as biomarkers of dietary fat intake and predictors for medical conditions is increasing. ObjectiveWe compared eleven dietary and the levels of 26 plasma phospholipid FAs in metabolically healthy and unhealthy phenotypes in black South African adults. MethodsAdults from the South African arm of the Prospective Urban and Rural Epidemiology study baseline (n = 711) were categorised into four groups, namely normal weight without metabolic syndrome (MetS) (MHNW), normal weight with MetS (MUNW), metabolically healthy overweight/obese (MHO) and metabolically unhealthy overweight/obese (MUO). Dietary and plasma phospholipid FAs were measured by a quantitative food frequency questionnaire and gas chromatography-tandem mass spectrometry, respectively. We compared dietary FAs, plasma phospholipid FAs, and estimated desaturase activity between the metabolic status groups using ANCOVA adjusted for age and energy intake. ResultsMetS was diagnosed in 35% of the participants. After adjustment for age and total energy intake, in comparison to the MHNW reference group, saturated dietary FAs (C14:0 to C18:0) and alpha-linolenic acid intakes were higher in both overweight/obese groups (MHO and MUO), while linoleic acid intakes were higher in the MUO group only. Plasma levels of most saturated FAs (C18:0 to C22:0) and PUFAs were higher, whereas selected MUFAs, palmitic acid, and estimated desaturase activities were lower in the overweight/obese groups. ConclusionsThe overweight groups generally had higher fat intakes than normal-weight groups, but lower plasma levels of palmitic, palmitoleic, oleic, cis-vaccenic and estimated desaturase activities. Therefore, in this population, lower plasma levels of palmitic, palmitoleic, oleic, and cis-vaccenic acids and decreased estimated desaturase activities may be biomarkers of abnormal metabolic health in overweight/obese study participants.