Relations of Metabolic Health and Obesity to Brain Aging in Young to Middle-Aged Adults.
ABSTRACT: Background We aimed to evaluate the association between metabolic health and obesity and brain health measured via magnetic resonance imaging and neurocognitive testing in community dwelling adults. Methods and Results Framingham Heart Study Third Generation Cohort members (n=2170, 46±9 years of age, 54% women) without prevalent diabetes, stroke, dementia, or other neurologic conditions were grouped by metabolic unhealthiness (≥2 criteria for metabolic syndrome) and obesity (body mass index ≥30 kg/m2): metabolically healthy (MH) nonobese, MH obese, metabolically unhealthy (MU) nonobese, and MU obese. We evaluated the relationships of these groups with brain structure (magnetic resonance imaging) and function (neurocognitive tests). In multivariable-adjusted analyses, metabolically unhealthy individuals (MU nonobese and MU obese) had lower total cerebral brain volume compared with the MH nonobese referent group (both P<0.05). Additionally, the MU obese group had greater white matter hyperintensity volume (P=0.004), whereas no association was noted between white matter hyperintensity volume and either groups of metabolic health or obesity alone. Obese individuals had less favorable cognitive scores: MH obese had lower scores on global cognition, Logical Memory-Delayed Recall and Similarities tests, and MU obese had lower scores on Similarities and Visual Reproductions-Delayed tests (all P≤0.04). MU and obese groups had higher free water content and lower fractional anisotropy in several brain regions, consistent with loss of white matter integrity. Conclusions In this cross-sectional cohort study of younger to middle-aged adults, poor metabolic health and obesity were associated with structural and functional evidence of brain aging. Improvement in metabolic health and obesity may present opportunities to improve long-term brain health.
Project description:Background The combined effect of transitions of metabolic health and weight on cardiovascular disease (CVD) remains unclear. We aimed to examine the association of concurrent changes of metabolic health and weight on CVD over time. Methods and Results The study population consisted of 205 394 from the Korean National Health Insurance Service. Metabolic health was determined by fasting serum glucose, total cholesterol, and blood pressure levels, while obesity was determined by body mass index. All participants were divided into either metabolically healthy nonobese (MHNO), metabolically healthy obese, metabolically unhealthy nonobese, or metabolically unhealthy obese for each of the first (2002-2003) and second (2004-2005) health screening periods, after which participants were followed-up for CVD from 2006 to 2015. Cox proportional hazards regression was used to determine adjusted hazard ratios (aHRs) and 95% CIs. Among initial MHNO participants, those who became metabolically healthy obese (aHR, 1.25; 95% CI, 1.10-1.41), metabolically unhealthy nonobese (aHR, 1.23; 95% CI, 1.15-1.31), and metabolically unhealthy obese (aHR, 1.34; 95% CI, 1.12-1.61) had elevated risk for CVD compared with those who remained MHNO. Conversely, improving metabolic health and obesity were associated with reduced CVD risk among initially metabolically unhealthy nonobese to secondary MHNO (aHR, 0.79; 95% CI, 0.73-0.84), metabolically unhealthy obese to MHNO (aHR, 0.68; 95% CI, 0.58-0.81), and metabolically unhealthy obese to metabolically healthy obese (aHR, 0.73; 95% CI, 0.66-0.80) participants. Conclusions Changes toward metabolically unhealthy or obese states resulted in increased CVD risk. Improving metabolic health along with reducing weight may lead to decreased risk of CVD.
Project description:Although obesity is clearly identified as a risk factor for hypertension, the association between its different metabolic phenotypes and hypertension remains unclear. We aimed to investigate this association and compare the degree of association between metabolic health and obesity phenotypes defined by 5 representative criteria and hypertension risk.This study used data from the China Health and Nutrition Survey 2009 wave, and the final analysis included 7632 subjects aged 18 to 85 years with available fasting blood samples and anthropometric measurements. Body mass index was used to define nonobese and obese status in subjects (cut-off value, 25?kg/m), and metabolic health state was respectively defined by 5 published criteria: the Adult Treatment Panel (ATP)-III, the Wildman, the Karelis, the homeostasis model assessment (HOMA), and the fasting blood glucose × triglyceride (TyG) criteria. Subjects were categorized into 4 phenotypes according to their metabolic health and obesity status: metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO).A total of 2171 subjects (28.4% of the study population) had hypertension, and hypertension prevalence was significantly increased as weight increased for both metabolically healthy and metabolically unhealthy subjects. Within the MHO phenotypes, the prevalence ranged from 22.7% to 38.6% according to the Wildman and HOMA criteria, respectively. Compared to the MHNO phenotype, the MHO phenotype had an increased risk of hypertension, and the adjusted odds ratios for hypertension in MHO subjects were 1.94 (95% confidence interval 1.60-2.35) using the ATP-III criteria, 1.98 (1.61-2.43) using the Wildman criteria, 2.37 (1.88-2.99) using the Karelis criteria, 2.26 (1.96-2.61) using the HOMA criteria, and 2.54 (2.14-3.00) using the TyG criteria, respectively. A similar significant pattern was found in the MUO and MUNO phenotypes for risk of hypertension. Furthermore, the MUO phenotype consistently revealed the strongest degree of association with hypertension, following by the MHO and the MUNO phenotype.Both metabolically unhealthy status and obese status contributed to a higher risk of hypertension in Chinese adults. The MHO phenotype was not a benign condition and had substantial risk of hypertension compared to the MHNO phenotype. Thus, metabolic health status and obesity should be monitored together when managing hypertension risk.
Project description:<h4>Background/aims</h4>The risk of recurrence of colorectal adenoma among obese individuals without metabolic abnormalities or in those with metabolically healthy obesity is largely unexplored. Therefore, we longitudinally investigated the risk of adenoma occurrence in individuals undergoing surveillance colonoscopy according to metabolic status and obesity.<h4>Methods</h4>This retrospective cohort study included 16,872 Korean adults who underwent their first screening colonoscopy between 2003 and 2012 and who then underwent follow-up colonoscopy until 2017. Participants were categorized into a metabolically healthy nonobese group (reference group), a metabolically healthy obese group, a metabolically abnormal nonobese group, and a metabolically abnormal obese group. Hazard ratios (HRs) for adenoma recurrence compared to the reference group were calculated in each group.<h4>Results</h4>During a median follow-up duration of 47.3 months (interquartile range, 35.6 to 58.9 months), 3,673 (21.8%) and 292 (1.73%) participants developed adenoma and advanced adenoma, respectively. When age, sex, smoking, alcohol consumption, family history of colorectal cancer, and baseline adenoma risk were adjusted, the risk of adenoma recurrence was increased in metabolically healthy obese individuals (HR, 1.33; 95% confidence interval [CI], 1.12 to 1.57) and metabolically abnormal obese individuals (HR, 1.18; 95% CI, 1.08 to 1.30) but not in metabolically abnormal nonobese individuals (HR, 1.03; 95% CI, 0.94 to 1.13).<h4>Conclusions</h4>In this study, metabolically healthy obese individuals and metabolically abnormal obese individuals exhibited increased risks of occurrence of colorectal adenoma diagnosed by surveillance colonoscopy. This finding implies that obesity itself, even without metabolic abnormalities, is associated with an increased risk of adenoma recurrence.
Project description:Few studies have described the characteristics of metabolically healthy individuals with excess fat in the Chinese population. This study aimed to prospectively investigate the natural course of metabolically healthy overweight/obese (MH-OW/OB) adults, and to assess the impact of weight change on developing metabolic abnormalities. During 2009-2010, 525 subjects without any metabolic abnormalities or other obesity-related diseases were evaluated and reevaluated after 5 years. The subjects were categorized into two groups of overweight/obese and normal weight based on the criteria of BMI by 24.0 at baseline. At follow-up, the MH-OW/OB subjects had a significantly increased risk of developing metabolically abnormalities compared with metabolically healthy normal-weight (MH-NW) individuals (risk ratio: 1.35, 95% confidence interval: 1.17-1.49, p value < 0.001). In the groups of weight gain and weight maintenance, the MH-OW/OB subjects was associated with a larger increase in fasting glucose, triglycerides, systolic blood pressure, diastolic blood pressure and decrease in high-density lipoprotein cholesterol comparing with MH-NW subjects. In the weight loss group, no significant difference of changes of metabolic parameters was observed between MH-OW/OB and MH-NW adults. This study verifies that MH-OW/OB are different from MH-NW subjects. Weight management is needed for all individuals since weight change has a significant effect on metabolic health without considering the impact of weight change according to weight status.
Project description:<h4>Background</h4>There is a current lack of consensus on defining metabolically healthy obesity (MHO). Limited data on dietary and lifestyle factors and MHO exist. The aim of this study is to compare the prevalence, dietary factors and lifestyle behaviours of metabolically healthy and unhealthy obese and non-obese subjects according to different metabolic health criteria.<h4>Method</h4>Cross-sectional sample of 1,008 men and 1,039 women aged 45-74 years participated in the study. Participants were classified as obese (BMI ? 30 kg/m(2)) and non-obese (BMI < 30 kg/m(2)). Metabolic health status was defined using five existing MH definitions based on a range of cardiometabolic abnormalities. Dietary composition and quality, food pyramid servings, physical activity, alcohol and smoking behaviours were examined.<h4>Results</h4>The prevalence of MHO varied considerably between definitions (2.2% to 11.9%), was higher among females and generally increased with age. Agreement between MHO classifications was poor. Among the obese, prevalence of MH was 6.8% to 36.6%. Among the non-obese, prevalence of metabolically unhealthy subjects was 21.8% to 87%. Calorie intake, dietary macronutrient composition, physical activity, alcohol and smoking behaviours were similar between the metabolically healthy and unhealthy regardless of BMI. Greater compliance with food pyramid recommendations and higher dietary quality were positively associated with metabolic health in obese (OR 1.45-1.53 unadjusted model) and non-obese subjects (OR 1.37-1.39 unadjusted model), respectively. Physical activity was associated with MHO defined by insulin resistance (OR 1.87, 95% CI 1.19-2.92, p = 0.006).<h4>Conclusion</h4>A standard MHO definition is required. Moderate and high levels of physical activity and compliance with food pyramid recommendations increase the likelihood of MHO. Stratification of obese individuals based on their metabolic health phenotype may be important in ascertaining the appropriate therapeutic or intervention strategy.
Project description:BMI, metabolic health status, and their interactions should be considered for estimating mortality risk; however, the data are controversial and unknown in Asians. We aimed to investigate this issue in Korean population. Total 323175 adults were followed-up for 96 (60-120) (median [5-95%]) months in a nationwide population-based cohort study. Participants were classified as "obese" (O) or "non-obese" (NO) using a BMI cut-off of 25?kg/m(2). People who developed ?1 metabolic disease component (hypertension, diabetes, dyslipidaemia) in the index year were considered "metabolically unhealthy" (MU), while those with none were considered "metabolically healthy" (MH). The MUNO group had a significantly higher risk of all-cause (hazard ratio, 1.28 [95% CI, 1.21-1.35]) and cardiovascular (1.88 [1.63-2.16]) mortality, whereas the MHO group had a lower mortality risk (all-cause: 0.81 [0.74-0.88]), cardiovascular: 0.73 [0.57-0.95]), compared to the MHNO group. A similar pattern was noted for cancer and other-cause mortality. Metabolically unhealthy status was associated with higher risk of all-cause and cardiovascular mortality regardless of BMI levels, and there was a dose-response relationship between the number of incident metabolic diseases and mortality risk. In conclusion, poor metabolic health status contributed more to mortality than high BMI did, in Korean adults.
Project description:<h4>Purpose</h4>Obese individuals have an increased risk of hypothyroidism. This study investigated the sex-specific association between obesity phenotypes and the development of hypothyroidism.<h4>Methods</h4>The study population was derived from a health management cohort in Shandong Provincial Hospital from 2012 to 2016. In total, 9011 baseline euthyroid adults were included and classified into four groups according to obesity phenotype: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUNO), and metabolically unhealthy obese (MUO). The median follow-up time was 1.92 (1.00-2.17) years. Incidence density was evaluated and a generalized estimation equation method was used to investigate the associations between obesity phenotypes and the development of hypothyroidism.<h4>Results</h4>The incidence densities of hypothyroidism in males with a consistent obesity phenotype were 12.19 (8.62-16.76), 15.87 (11.39-21.56), 14.52 (6.74-27.57), and 19.88 (14.06-27.34) per 1000 person-years in the MHNO, MHO, MUNO, and MUO groups, respectively. After adjusting for confounding factors, compared with the MHNO phenotype, the MHO, MUNO, and MUO phenotypes were independent risk factors for developing hypothyroidism in males. In the subgroup analysis, the MHO and MUO phenotypes were independent risk factors for developing hypothyroidism in males under 55 years, while the MUNO phenotype was an independent risk factor in males over 55 years. The MHO, MUNO, and MUO phenotypes were not independent risk factors for hypothyroidism in females.<h4>Conclusion</h4>Both obesity and metabolic abnormities are associated with a higher risk of hypothyroidism in males. The underlying mechanism of the sex and age differences in this association needs further investigation.
Project description:<h4>Objective</h4>Atrial fibrillation (AF) is associated with both obesity and its metabolic consequences. However, there is a paucity of information on whether the dynamic change of metabolic health and obesity phenotypes affect the risk of AF. We aimed to prospectively examine the association between metabolic health and its change over time and AF risk across body mass index (BMI) categories.<h4>Methods</h4>A total of 58,483 participants without history of cancer, and cardiovascular diseases from the Kailuan study were included in the present study. Transition of metabolic phenotypes was evaluated between 1st survey (2006-2007) and the 2nd survey (2008-2009). The hazard ratios (HRs) and 95% confidence intervals (CIs) for AF were assessed by Cox proportional hazards regression.<h4>Results</h4>During a median follow-up of 3 years, we documented 580 cases of AF. Compared with metabolically healthy individuals with normal weight, the multivariable-adjusted hazard ratios for metabolically healthy and unhealthy overweight/obese were 1.27 (95% <i>CI</i>: 1.01, 1.59) and 1.37 (95% <i>CI</i>: 1.09, 1.72), respectively. However, when transition was taken into account, overweight/obese people who maintained metabolically healthy status were not associated with increased long-term risk (<i>HR</i>, 1.11;95% <i>CI</i>: 0.70, 1.78), whereas participants who converted from metabolically healthy overweight/obese status to an unhealthy phenotype had higher AF risk than those who maintained metabolically healthy normal weight (<i>HR</i> 1.59, 95% <i>CI</i>: 1.11, 2.26). When BMI and metabolically healthy status were updated over the course of the study, significant short-term elevations in AF risk were associated with individuals with stable MU-OW/OB status.<h4>Conclusion</h4>In this community-based cohort study, metabolically healthy overweight/obese individuals have increased risks of AF. Obesity remains a risk factor for AF independent of major metabolic factors. Our data further suggested that metabolic phenotype was a dynamic condition, and maintenance of metabolic health and normal weight might alleviate the risk of AF.
Project description:The debate regarding the actual cardiovascular burden in metabolically healthy obese or metabolically unhealthy non-obesity individuals is ongoing. Accumulating data have suggested a unique pathophysiological role of pro-inflammatory cytokines in mediating metabolic and cardiovascular disorders by dysregulated visceral adiposity. To compare the burden of visceral adiposity, the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and the prevalent atherosclerotic burden in metabolically healthy obese (MHO) or metabolically unhealthy (MU) populations, were compared to those of metabolically healthy non-obesity subjects (MHNO). Coronary artery calcification score (CACS) and visceral fat, including pericardial fat (PCF)/thoracic peri-aortic fat (TAT), were quantified in 2846 asymptomatic subjects using a CT dataset. A cross-sectional analysis comparing CACS, inflammatory marker hs-CRP, and visceral fat burden among four obesity phenotypes (MHNO, metabolically unhealthy non-obesity (MUNO), MHO, and metabolically unhealthy obese (MUO)) was performed. Both MUNO and MUO demonstrated significantly higher hs-CRP and greater CACS than MHNO/MHO (adjusted coefficient: 25.46, 95% confidence interval (CI): 5.29-45.63; 43.55, 95% CI: 23.38-63.73 for MUNO and MUO (MHNO as reference); both <i>p</i> < 0.05). Visceral fat (PCF/TAT) was an independent determinant of MU and was similarly higher in the MUNO/MHO groups than in the MHNO group, with the MUO group having the largest amount. PCF/TAT, obesity, and MU remained significantly associated with higher CACS even after adjustment, with larger PCF/TAT modified effects for MU and diabetes in CACS (both p<sub>interaction</sub> < 0.05). MU tightly linked to excessive visceral adiposity was a strong and independent risk factor for coronary atherosclerosis even in lean individuals, which could be partially explained by its coalignment with pathological pro-inflammatory signaling.
Project description:OBJECTIVES:In the general population, metabolic health often declines as BMI increases. However, some obese individuals maintain metabolic health. HIV and antiretroviral therapy have been associated with metabolic disturbances. We hypothesized that HIV-infected (HIV) men on suppressive antiretroviral therapy experience less metabolic health than HIV-uninfected (HIV) men across all BMI categories. DESIGN/METHODS:In a cross-sectional analysis of 1018 HIV and 1092 HIV men enrolled in the multicenter AIDS cohort study, Poisson regression with robust variance determined associations between HIV serostatus and metabolic health prevalence (defined as meeting ?2 of 5 National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria), adjusting for age, race, BMI category, smoking, and hepatitis C virus infection status. RESULTS:HIV men were younger (54 vs. 59 years) and had lower median BMI (25 vs. 27?kg/m). Nonobese HIV men had lower metabolic health prevalence than HIV men (BMI ?25?kg/m: 80 vs. 94%, P?<?0.001; BMI 25-29?kg/m: 64 vs. 71%, P?=?0.05), but metabolic health prevalence among obese men did not differ by HIV serostatus (BMI 30-34?kg/m: 35 vs. 39%, P?=?0.48; BMI ?35?kg/m: 27 vs. 25%, P?=?0.79). In the adjusted model, nonobese HIV men were less likely to demonstrate metabolic health than nonobese HIV men. Among HIV men, per year darunavir, zidovudine, and stavudine use were associated with lower metabolic health likelihood. CONCLUSION:Metabolically healthy obesity prevalence does not differ by HIV serostatus. However, among nonobese men, HIV infection is associated with lower metabolic health prevalence, with associations between lack of metabolic health and darunavir and thymidine analog nucleoside reverse transcriptase inhibitor exposure observed.