Metabolically Healthy Obesity and Risk of Kidney Function Decline.
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ABSTRACT:
SUBMITTER: Chang AR
PROVIDER: S-EPMC5866209 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
Publications
Metabolically Healthy Obesity and Risk of Kidney Function Decline.
Chang Alex R AR Surapaneni Aditya A Kirchner H Lester HL Young Amanda A Kramer Holly J HJ Carey David J DJ Appel Lawrence J LJ Grams Morgan E ME
Obesity (Silver Spring, Md.) 20180302 4
<h4>Objective</h4>The aim of this study was to examine the association between BMI categories, stratified by metabolic health status, and the risk of kidney function decline (KFD).<h4>Methods</h4>In this study, 42,128 adult patients with a stable BMI were classified over a 3-year baseline window by BMI and metabolic health status (assessed by Adult Treatment Panel-III criteria). KFD was defined as an estimated glomerular filtration rate (eGFR) decline ≥ 30%, eGFR < 15 mL/min/1.73 m<sup>2</sup> , ...[more]
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Project description:BACKGROUND:Debate over the cardiometabolic risk associated with metabolically healthy obesity (MHO) continues. Many studies have investigated this relationship by examining MHO at baseline with longitudinal follow-up, with inconsistent results. OBJECTIVES:The authors hypothesized that MHO at baseline is transient and that transition to metabolic syndrome (MetS) and duration of MetS explains heterogeneity in incident cardiovascular disease (CVD) and all-cause mortality. METHODS:Among 6,809 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) the authors used Cox proportional hazards and logistic regression models to investigate the joint association of obesity (?30 kg/m2) and MetS (International Diabetes Federation consensus definition) with CVD and mortality across a median of 12.2 years. We tested for interaction and conducted sensitivity analyses for a number of conditions. RESULTS:Compared with metabolically healthy normal weight, baseline MHO was not significantly associated with incident CVD; however, almost one-half of those participants developed MetS during follow-up (unstable MHO). Those who had unstable MHO had increased odds of CVD (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.14 to 2.25), compared with those with stable MHO or healthy normal weight. Dose response for duration of MetS was significantly and linearly associated with CVD (1 visit with MetS OR: 1.62; 95% CI: 1.27 to 2.07; 2 visits, OR: 1.92; 95% CI: 1.48 to 2.49; 3+ visits, OR: 2.33; 95% CI: 1.89 to 2.87; p value for trend <0.001) and MetS mediated approximately 62% (44% to 100%) of the relationship between obesity at any point during follow-up and CVD. CONCLUSIONS:Metabolically healthy obesity is not a stable or reliable indicator of future risk for CVD. Weight loss and lifestyle management for CVD risk factors should be recommended to all individuals with obesity.
| S-EPMC6002856 | biostudies-literature
Project description:Background Epidemic levels of CKD of undetermined cause, termed Mesoamerican nephropathy in Central America, have been found in low- and middle-income countries. We investigated the natural history of, and factors associated with, loss of kidney function in a population at high risk for this disease.Methods We conducted a 2-year prospective, longitudinal study with follow-up every 6 months in nine rural communities in northwestern Nicaragua and included all men (n=263) and a random sample of women (n=87) ages 18-30 years old without self-reported CKD, diabetes, or hypertension. We used growth mixture modeling to identify subgroups of eGFR trajectory and weighted multinomial logistic regression to examine associations with proposed risk factors.Results Among men, we identified three subpopulations of eGFR trajectory (mean baseline eGFR; mean eGFR change over follow-up): 81% remained stable (116 ml/min per 1.73 m2; -0.6 ml/min per 1.73 m2 per year), 9.5% experienced rapid decline despite normal baseline function (112 ml/min per 1.73 m2; -18.2 ml/min per 1.73 m2 per year), and 9.5% had baseline dysfunction (58 ml/min per 1.73 m2; -3.8 ml/min per 1.73 m2 per year). Among women: 96.6% remained stable (121 ml/min per 1.73 m2; -0.6 ml/min per 1.73 m2 per year), and 3.4% experienced rapid decline (132 ml/min per 1.73 m2; -14.6 ml/min per 1.73 m2 per year; n=3 women). Among men, outdoor and agricultural work and lack of shade availability during work breaks, reported at baseline, were associated with rapid decline.Conclusions Although Mesoamerican nephropathy is associated with agricultural work, other factors may also contribute to this disease.
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Project description:BACKGROUND:Whether being metabolically healthy obese (MHO)-defined by the presence of obesity in the absence of metabolic syndrome-is associated with subsequent cardiovascular disease (CVD) remains unclear and may depend on the participants' age. We examined the association of being MHO with CVD risk in the elderly. METHODS AND FINDINGS:This study included 5,314 individuals (mean age 68 years) from the prospective population-based Rotterdam Study. We categorized our population in groups according to body mass index (BMI) and presence and absence of metabolic syndrome, and estimated the hazard ratio (HR) and 95% confidence interval (95%CI) for every group by using Cox proportional hazard models. Among 1048 (19.7%) obese individuals we identified 260 (24.8%) MHO subjects. Over 14 years of follow-up there were 861 incident CVD cases. In the multivariable adjusted analysis, we did not observe an increased CVD risk in MHO individuals (HR 1.07, 95%CI 0.75-1.53), compared to normal weight individuals without metabolic syndrome. CVD risk was increased by the presence of metabolic syndrome in normal weight (HR 1.35, 95%CI 1.02-1.80), overweight (HR 1.32, 95%CI 1.09-1.60) and obese (HR 1.33, 95%CI 1.07-1.66) individuals, compared to those with normal weight without metabolic syndrome. In a mediation analysis, 71.3% of the association between BMI and CVD was explained by the presence of metabolic syndrome. CONCLUSIONS:In our elderly population, we found that the presence of obesity without metabolic syndrome did not confer a higher CVD risk. However, metabolic syndrome was strongly associated with CVD risk, and was associated with an increased risk in all BMI categories. Therefore, preventive interventions targeting cardiometabolic risk factors could be considered in elderly, regardless of weight status.
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Project description:Although obesity is typically associated with metabolic dysfunction and cardiometabolic diseases, some people with obesity are protected from many of the adverse metabolic effects of excess body fat and are considered "metabolically healthy." However, there is no universally accepted definition of metabolically healthy obesity (MHO). Most studies define MHO as having either 0, 1, or 2 metabolic syndrome components, whereas many others define MHO using the homeostasis model assessment of insulin resistance (HOMA-IR). Therefore, numerous people reported as having MHO are not metabolically healthy, but simply have fewer metabolic abnormalities than those with metabolically unhealthy obesity (MUO). Nonetheless, a small subset of people with obesity have a normal HOMA-IR and no metabolic syndrome components. The mechanism(s) responsible for the divergent effects of obesity on metabolic health is not clear, but studies conducted in rodent models suggest that differences in adipose tissue biology in response to weight gain can cause or prevent systemic metabolic dysfunction. In this article, we review the definition, stability over time, and clinical outcomes of MHO, and discuss the potential factors that could explain differences in metabolic health in people with MHO and MUO - specifically, modifiable lifestyle factors and adipose tissue biology. Better understanding of the factors that distinguish people with MHO and MUO can produce new insights into mechanism(s) responsible for obesity-related metabolic dysfunction and disease.
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Project description:When humans eat more and exercise less, they tend to become obese and unhealthy. The molecular pathways that link obesity to serious diseases like Type 2 diabetes and cardiovascular disease have become a subject of intensive scientific investigation because the exploding prevalence of obesity worldwide represents a grave new threat to the health of hundreds of millions of people. However, obesity is not always destiny. Two important clinical populations have been valuable to understand the mechanisms behind this conundrum: individuals who exhibit metabolic dysfunction, diabetes and elevated cardiovascular disease risk despite a lean body type, and individuals who are relatively protected from these dangers despite significant obesity. Study of this second group of 'metabolically healthy obese' people in particular has been revealing because such individuals exhibit specific, identifiable, anatomic, cellular and molecular features that set them apart from the rest of us who suffer declining health with increasing weight. Here, we examine some of these features, including some mouse models that are informative of mechanism, and suggest hypotheses for further study, including the possibility that genes and pathways of the immune system might offer new diagnostic or therapeutic targets.
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Project description:BackgroundWhether metabolically healthy obese (MHO) individuals are at increased risk of ischemic stroke is not well known. We investigated the association of the MHO phenotype with ischemic stroke.MethodsA total of 354,083 adults (age 45.8 ± 14.2 years) from the Korean National Health Insurance Service-National Sample Cohort enrolled in 2004-2008 were followed-up for incident ischemic stroke until 2013. Subjects meeting none of the metabolic syndrome criteria were classified as 'metabolically healthy'. The cohort was categorized into four groups according to obesity and metabolic status: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), MHO, and metabolically unhealthy obese (MUO).ResultsIschemic stroke was newly diagnosed in 4,884 (1.4%) individuals during a mean follow-up of 7.4 ± 1.5 years. Stroke incidence rates for the MHNW, MUNW, MHO, and MUO groups were 0.56, 2.61, 0.61, and 2.76 per 1,000 person-years, respectively. While risk for stroke increased significantly in metabolically unhealthy groups, it was not increased in MHO compared to the MHNW group on multivariate analysis. In metabolically healthy individuals, obesity did not increase the risk for ischemic stroke, regardless of the severity of obesity. Meanwhile, in metabolically unhealthy individuals, being obese was significantly associated with increased risk of stroke.ConclusionsMHO individuals were not at increased risk for ischemic stroke. However, obesity increased risk for ischemic stroke in persons with metabolic risk factors; therefore, maintaining normal weight may be more important for this population. Also, metabolic unhealthiness showed greater association than obesity with stroke.
| S-EPMC5877885 | biostudies-literature
Project description:Background/objectivesSome obese adults have a normal metabolic profile and are considered 'healthy', but whether they experience faster ageing than healthy normal-weight adults is unknown. We compared decline in physical function, worsening of bodily pain and likelihood of future mobility limitation and disability between these groups.Subjects/methodsThis was a population-based observational study using repeated measures over 2 decades (Whitehall II cohort data). Normal-weight (body mass index (BMI) 18.5-24.9 kg m-2), overweight (25.0-29.9 kg m-2) and obese (⩾30.0 kg m-2) adults were considered metabolically healthy if they had 0 or 1 of 5 risk factors (hypertension, low high-density lipoprotein cholesterol, high triacylglycerol, high blood glucose and insulin resistance) in 1991/1994. Decline in physical function and worsening of bodily pain based on change in Short Form Health Survey items using eight repeated measures over 18.8 years (1991/1994-2012/2013) were compared between metabolic-BMI groups using linear mixed models. Odds of mobility limitation based on objective walking speed (slowest tertile) and of disability based on limitations in ⩾1 of 6 basic activities of daily living, each using three repeated measures over 8.3 years (2002/2004-2012/2013), were compared using logistic mixed models.ResultsIn multivariable-adjusted mixed models on up to 6635 adults (initial mean age 50 years; 70% male), healthy normal-weight adults experienced a decline in physical function of -3.68 (95% CI=-4.19, -3.16) score units per decade; healthy obese adults showed an additional -3.48 (-4.88, -2.08) units decline. Healthy normal-weight adults experienced a -0.49 (-1.11, 0.12) score unit worsening of bodily pain per decade; healthy obese adults had an additional -2.23 (-3.78, -0.69) units worsening. Healthy obesity versus healthy normal-weight conferred 3.39 (2.29, 5.02) times higher odds of mobility limitation and 3.75 (1.94, 7.24) times higher odds of disability.ConclusionsOur results suggest that obesity, even if metabolically healthy, accelerates age-related declines in functional ability and poses a threat to independence in older age.
| S-EPMC5467240 | biostudies-literature