Review ArticleAre there persons who are obese, but metabolically healthy?
Abstract
The aim of this article was to review the evidence for a metabolically normal subset of the obese and its implications for clinical and research work. The methods included literature review and correspondence with authors. Since 1947, when Vague described a relation between distribution of body fat and the risk factors for cardiovascular disease, much evidence has suggested that early onset of the obesity, hyperplasia of normal adipocytes, and normal quantities of visceral abdominal fat may be associated with a favorable metabolic response in obese subjects. Analyses in 1973 by Keyes and later by Reuben Andres in 1980 suggested that obesity for some was not a risk factor and might even be an asset. Recently, in the study by Bonora et al of the relation between insulin resistance and the 4 main disorders of the metabolic syndrome in the Bruneck epidemiologic study, a subgroup of obese individuals with a normal metabolic response was evident. In a current study by Brochu et al of an obese metabolically normal subgroup of postmenopausal women, visceral abdominal fat estimated by computed tomography (CT) scan and age of onset were significant variables. The obese, metabolically normal subgroup (OBMN) must be taken into consideration in both clinical and research work. Persons with OBMN and their parents may be wrongly blamed because of the obesity. Attempts at weight loss may be counterproductive. The criteria for selection of obese research subjects may favor inclusion of an OBMN subset, which may invalidate statistical analysis. Findings suggesting the OBMN subset include family members with uncomplicated obesity, early onset of the obesity, fasting plasma insulin within normal range, and normal distribution of the excess fat. Hormonal, genetic studies, and prospective studies will help to clarify the significance and underlying mechanisms of this subset.
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Adipose failure through adipocyte overload and autoimmunity
2024, Autoimmunity ReviewsMetabolic syndrome poses a great worldwide threat to the health of the patients. Increased visceral adiposity is recognized as the main determinant of the detrimental clinical effects of insulin resistance. Inflammation and immune system activation in the adipose tissue (AT) have a central role in the pathophysiology of metabolic syndrome, but the mechanisms linking increased adiposity to immunity in the AT remain in part elusive. In this review, we support the central role of adipocyte overload and relative adipose failure as key determinants in triggering immune aggression to AT. This provides a mechanistic explanation of the relative metabolic wellness of metabolically normal obese people and the disruption in insulin signaling in metabolically obese lean people.
Clinical Outcomes in Metabolically Healthy and Unhealthy Obese and Overweight Patients With Atrial Fibrillation: Findings From the GLORIA-AF Registry
2024, Mayo Clinic ProceedingsTo explore the association between metabolic status, body mass index (BMI), and natural history of patients with atrial fibrillation (AF).
The global, prospective GLORIA-AF Registry Phase II and III included patients with recent diagnosis of AF between November 2011 and December 2014 for Phase II and between January 2014 and December 2016 for Phase III. With this analysis, we categorized patients with AF according to BMI (normal weight [18.5 to 24.9 kg/m2], overweight [25.0 to 29.9 kg/m2], obese [30.0 to 60.0 kg/m2]) and metabolic status (presence of hypertension, diabetes, and hyperlipidemia). We analyzed risk of major outcomes using multivariable Cox regression analyses; the primary outcome was the composite of all-cause death and major adverse cardiovascular events.
There were 24,828 (mean age, 70.1±10.3 years; 44.6% female) patients with AF included. Higher BMI was associated with metabolically unhealthy status and higher odds of receiving oral anticoagulants and other treatments. Normal-weight unhealthy patients showed a higher risk of the primary composite outcome (adjusted hazard ratio [aHR], 1.20; 95% CI, 1.01 to 1.42) and thromboembolism, whereas a lower risk of cardiovascular death (aHR, 0.35; 95% CI, 0.14 to 0.88) and major adverse cardiovascular events (aHR, 0.56; 95% CI, 0.33 to 0.93) was observed in metabolically healthy obese individuals. Unhealthy metabolic groups were also associated with increased risk of major bleeding (aHR, 1.51 [95% CI, 1.04 to 2.20] and aHR, 1.96 [95% CI, 1.34 to 2.85] in overweight and obese groups, respectively).
Increasing BMI was associated with poor metabolic status and with more intensive treatment. Prognosis was heterogeneous between BMI groups, with metabolically unhealthy patients showing higher risk of adverse events.
Prevalence of liver cirrhosis based on the metabolic health and weight criteria: Report from the Korea National Health and Nutrition Examination Survey (KNHANES) data analysis
2023, Annals of HepatologyRecent studies have proposed two distinctive types of obesity, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO), based on various physiological factors. This study sought to explore the relationship between the metabolic obesity types and the incidence of liver cirrhosis (LC) in a large nationally-representative population.
Data on 27,629 adults with MHO or MUHO, were analyzed from the Korea National Health and Nutrition Examination Survey (KNHANES) obtained from 2015 through 2019. Four categories of metabolic health and weight (MHW) were generated for analysis: (1) MHO, (2) MUHO, (3) Metabolically unhealthy normal weight (MUHNW), and (4) Metabolically healthy normal weight (MHNW). Statistical analyzes were performed with univariate and multivariate logistic regression.
The prevalence of LC did not show statistically significant differences among the MHW categories: 0.5% in MHO, 0.4% in MUHO, 0.2% in MHNW, and 0.3% in MUHNW. The unadjusted analysis showed a significant association between self-reported LC and MUHO, but this association was not evident in the adjusted analysis. In the adjusted analysis of the prevalence of laboratory LC, a significant association emerged in the MUHO group, followed in descending order of magnitude by the MHO and MUHNW groups. A favorable fasting blood glucose level was the only factor associated with increased prevalence of reported LC in MUHO.
The study demonstrated a difference in the prevalence of LC between MHO and MUHO. Our study concludes that the MHO phenotype is a transient status with regard to metabolic abnormalities, and caution is necessary when evaluating MHO.
Metabolically healthy obesity: Misleading phrase or healthy phenotype?
2023, European Journal of Internal MedicineObesity is a heterogenous condition with multiple different phenotypes. Among these a particular subtype exists named as metabolically healthy obesity (MHO). MHO has multiple definitions and its prevalence varies according to study. The potential mechanisms underlying the pathophysiology of MHO include the different types of adipose tissue and their distribution, the role of hormones, inflammation, diet, the intestinal microbiota and genetic factors. In contrast to the negative metabolic profile associated with metabolically unhealthy obesity (MUO), MHO has relatively favorable metabolic characteristics. Nevertheless, MHO is still associated with many important chronic diseases including cardiovascular disease, hypertension, type 2 diabetes, chronic kidney disease as well as certain types of cancer and has the risk of progression into the unhealthy phenotype. Therefore, it should not be considered as a benign condition. The major therapeutic alternatives include dietary modifications, exercise, bariatric surgery and certain medications including glucagon-like peptide-1 (GLP-1) analogs, sodium-glucose cotransporter-2 (SGLT-2) inhibitors and tirzepatide. In this review, we discuss the significance of MHO while comparing this phenotype with MUO.
Circulating 25-hydroxyvitamin D is associated with metabolic phenotypes of obesity: National Food and Nutrition Surveillance
2023, Nutrition ResearchDifferent phenotypes of obesity are each related with different complications and comorbidities. We hypothesized that suboptimal vitamin D status is directly associated with an unhealthy metabolic status, especially if allied with obesity. This cross-sectional study was performed in the framework of the National Food and Nutrition Surveillance. Overall, 1098 men and women participated in this study. In addition to height and weight, serum concentrations of 25-hydroxyvitamin D (25(OH)D) and glycemic and lipidemic status were evaluated. Then participants were classified into 4 groups based on body mass index and lipidemic and glycemic profile status, as follows: hyperglycemic-dyslipidemic obese (HDO), hyperglycemic-dyslipidemic nonobese (HDNO), normoglycemic-normolipidemic obese (NNO), and normoglycemic-normolipidemic nonobese (NNNO). In this study, 31.6% of participants were classified as HDO, 7.5% as HDNO, 34.5% as NNO, and 26.4% as NNNO. The frequency of suboptimal vitamin D status was more prevalent in HDO (81.8%) than in other phenotypes (HDNO, 80%; NNO, 77.6%; NNNO, 73.8%; P = .015). In the multivariate model, suboptimal vitamin D status significantly increased the odds of being NNO (odds ratio [OR], 1.28; 95% CI, 0.84-1.95), HDNO (OR, 1.48; 95% CI, 0.77-2.83), and HDO (OR, 1.73; 95% CI, 1.11-2.7) compared with the NNNO group. Likewise, in multivariate model, per each unit (ng/mL) increment in 25(OH)D concentration, the odds of HDNO and HDO decreased significantly by 4% (OR, 0.96; 95% CI, 0.94-0.98) and 7% (OR, 0.93; 95% CI, 0.92-0.95), respectively. The results of the study showed a significant relationship between serum 25(OH)D concentrations and metabolic obesity phenotypes; these data confirm the association between suboptimal vitamin D status and metabolic complications, especially in obese individuals.
Circulating microRNA levels differ in the early stages of insulin resistance in prepubertal children with obesity
2023, Life SciencesCitation Excerpt :This escalates the risk for the development of several obesity-related complications early in life, especially early development of type 2 diabetes (T2DM) and cardiovascular disease, which are two major causes of death worldwide [1]. However, a substantial part of the population with obesity display a phenotype that can be described as metabolically “healthy” (MHO), in which subjects display a lower degree of metabolic complications despite the presence of clinically defined obesity [4–8]. However, it is still unclear whether MHO subjects remain metabolically healthy or if at some point, they become metabolically unhealthy (MUO).
The increasing prevalence of childhood obesity escalates the risk for related complications. Circulating microRNAs (miRNAs) have been suggested as good predictive markers of insulin resistance in those with obesity. The aim was to identify a circulating miRNA profile that reflects insulin resistance in prepubertal children with obesity.
Plasma miRNAs were measured in prepubertal children (n = 63, 5–9 years) using TaqMan Advanced miRNA Human Serum/Plasma plates and then were validated by RT-qPCR. Subjects were divided into normal weight (n = 20, NW) and overweight or obese (n = 43, OW/OB) groups according to their BMI z-scores. The OW/OB group was further subdivided into insulin sensitive or metabolically healthy obese (n = 26, MHO) and insulin resistant or metabolically unhealthy obese (n = 17, MUO) according to HOMA-IR.
While no differences were observed in the fasting plasma glucose levels, serum insulin levels were significantly elevated in the OW/OB compared to the NW group. Of 188 screened miRNAs, eleven were differentially expressed between the NW and OW/OB groups. Validation confirmed increased circulating levels of miR-146a-5p and miR-18a-5p in the OW/OB group, which correlated with BMI z-score. Interestingly, miR-146a-5p was also correlated with HOMA-IR index. While only miR-18a-5p was upregulated in the OW/OB children, independently of their degree of insulin sensitivity, miR-146-5p, miR-423-3p and miR-152-3p were associated with insulin resistance.
The present study provides evidence of molecular alterations that occur early in life in prepubertal obesity. These alterations may potentially be crucial for targeted prevention or prompt precision therapeutic development and subsequent interventions.