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Baniasad A, Najafzadeh MJ, Najafipour H, Gozashti MH. The prevalence of metabolically healthy obesity and its transition into the unhealthy state: A 5-year follow-up study. Clin Obes 2024; 14:e12691. [PMID: 38978306 DOI: 10.1111/cob.12691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 04/12/2024] [Accepted: 06/14/2024] [Indexed: 07/10/2024]
Abstract
People with metabolically healthy obesity (MHO) are at risk of developing cardiometabolic diseases. We investigated the prevalence of MHO and factors influencing its transition into a metabolically unhealthy state (MUS). This study was conducted as part of the Kerman Coronary Artery Disease Risk Factor Study (KERCADRS). From 2014 to 2018, 9997 people were evaluated. The obesity and metabolic status of the MHO participants were re-examined after 5 years of their initial participation in the study. Out of 347 MHO, 238 individuals were accessed at follow-up. Twenty-nine (12.2%) had metabolic unhealthy normal weight (MUNW), 169 (71.0%) had metabolic unhealthy obesity (MUO), and the others had healthy metabolic state. Among age, total cholesterol, diastolic blood pressure and triglyceride (TG) variables, the baseline serum TG level was associated with a significant increase in the risk of developing MUS during 5 years (p <.05). The TG level optimal cut-off point for predicting the development into MUS was 107 mg/dL with 62.1% sensitivity and 77.5% specificity (AUC = 0.734, p <.001). A high percentage of MHO people transit into MUS during 5 years. A TG level higher than 107 mg/dL can help to identify people at a higher risk of developing into MUS.
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Affiliation(s)
- Amir Baniasad
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Hamid Najafipour
- Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Hossein Gozashti
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
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Ezeh U, Chen YI, Pall M, Buyalos RP, Chan JL, Pisarska MD, Azziz R. Alterations in nonesterified free fatty acid trafficking rather than hyperandrogenism contribute to metabolic health in obese women with polycystic ovary syndrome. Fertil Steril 2024; 121:1040-1052. [PMID: 38307453 DOI: 10.1016/j.fertnstert.2024.01.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 01/24/2024] [Accepted: 01/24/2024] [Indexed: 02/04/2024]
Abstract
OBJECTIVE To determine whether alterations in nonesterified fatty acid (NEFA) dynamics or degree of hyperandrogenism (HA) contribute to the difference in insulin sensitivity between women with metabolically healthy obese polycystic ovary syndrome (PCOS) (MHO-PCOS) and women with metabolically unhealthy obese PCOS (MUO-PCOS). DESIGN Prospective cross-sectional study. SETTING Tertiary-care academic center. PATIENTS One hundred twenty-five obese women with PCOS. INTERVENTION Consecutive obese (body mass index [BMI] ≥ 30 kg/m2) oligo-ovulatory women (n = 125) with PCOS underwent an oral glucose tolerance test and a subgroup of 16 participants underwent a modified frequently sampled intravenous glucose tolerance test to determine insulin-glucose and -NEFA dynamics. MAIN OUTCOME MEASURES Degree of insulin resistance (IR) in adipose tissue (AT) basally (Adipo-IR) and dynamically (the nadir in NEFA levels observed [NEFAnadir], the time it took for NEFA levels to reach nadir [TIMEnadir], and the percent suppression in plasma NEFA levels from baseline to nadir [%NEFAsupp]); peak lipolysis rate (SNEFA) and peak rate of NEFA disposal from plasma pool (KNEFA); whole-body insulin-glucose interaction (acute response of insulin to glucose [AIRg], insulin sensitivity index [Si], glucose effectiveness [Sg], and disposition index [Di]); and HA (hirsutism score, total and free testosterone levels, and dehydroepiandrosterone sulfate levels). RESULTS A total of 85 (68%) women were MUO-PCOS and 40 (32%) were MHO-PCOS using the homeostasis model of assessment of IR. Subjects with MUO-PCOS and MHO-PCOS did not differ in mean age, BMI, waist-to-hip ratio, HA, and lipoprotein levels. By a modified frequently sampled intravenous glucose tolerance test, eight women with MUO-PCOS had lesser Si, KNEFA, and the percent suppression in plasma NEFA levels from baseline to nadir (%NEFAsupp) and greater TIMEnadir, NEFAnadir, and baseline adipose tissue IR index (Adipo-IR) than eight subjects with MHO-PCOS, but similar fasting NEFA levels and SNEFA. Women with MUO-PCOS had a higher homeostasis model of assessment-β% and fasting insulin levels than women with MHO-PCOS. In bivalent analysis, Si correlated strongly and negatively with Adipo-IR and NEFAnadir, weakly and negatively with TIMEnadir, and positively with KNEFA and %NEFAsupp, in women with MUO-PCOS only. CONCLUSION Independent of age and BMI, women with MUO-PCOS have reduced NEFA uptake and altered insulin-mediated NEFA suppression, but no difference in HA, compared with women with MHO-PCOS. Altered insulin-mediated NEFA suppression, rather than HA or lipolysis rate, contributes to variations in insulin sensitivity among obese women with PCOS.
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Affiliation(s)
- Uche Ezeh
- California IVF Fertility Center, Sacramento, California; Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California; Department of Obstetrics and Gynecology, Heersink School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama; Department of Obstetrics and Gynecology, Alta Bates Summit Medical Center (Sutter), Berkeley, California
| | - Yd Ida Chen
- Department of Pediatrics and Medicine, Harbor- University of California (UCLA) Medical Center, Torrance, California; Department of Medicine, The David Geffen School of Medicine, UCLA, Los Angeles, California
| | - Marita Pall
- Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Richard P Buyalos
- Fertility and Surgical Associates of California, Thousand Oaks, California
| | - Jessica L Chan
- Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Margareta D Pisarska
- Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California; Department of Obstetrics and Gynecology, UCLA, Los Angeles, California
| | - Ricardo Azziz
- Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California; Department of Obstetrics and Gynecology, Heersink School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama; Department of Medicine, Heersink School of Medicine, UAB, Birmingham, Alabama; Department of Healthcare Organization and Policy, School of Public Health, UAB, Birmingham, Alabama; Department of Health Policy, Management and Behavior, School of Public Health, State University of New York at Albany, Albany, New York.
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Netto AM, Kashiwagi NM, Minanni CA, Santos RD, Cesena FY. Adiposity, hepatic steatosis, and metabolic health transitions in people with obesity: Influences of age and sex. Nutr Metab Cardiovasc Dis 2023; 33:1149-1157. [PMID: 37095017 DOI: 10.1016/j.numecd.2023.03.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 03/19/2023] [Accepted: 03/27/2023] [Indexed: 04/26/2023]
Abstract
BACKGROUND AND AIMS Metabolically healthy (MHO) and unhealthy obesity (MUO) may be transient conditions. This study aimed to quantify and identify predictive factors of metabolic transitions in obesity, exploring influences of age and sex. METHODS AND RESULTS We retrospectively evaluated adults with obesity who underwent routine health evaluation. In a cross-sectional analysis of 12,118 individuals (80% male, age 44.3 ± 9.9 years), 16.8% had MHO. In a longitudinal evaluation of 4483 participants, 45.2% of individuals with MHO at baseline had dysmetabolism after a median follow-up of 3.0 (IQR 1.8-5.2) years, whereas 13.3% MUO participants became metabolically healthy (MH). Development of hepatic steatosis (HS, ultrasound) was an independent predictor of MHO conversion to dysmetabolism (OR 2.36; 95% CI 1.43, 3.91; p < 0.001), while HS persistence was inversely associated with transition from MUO to MH status (OR 0.63; 95% CI 0.47, 0.83; p = 0.001). Female sex and older age were associated with a lower chance of MUO regression. A 5% increment in body mass index (BMI) over time increased the likelihood of metabolic deterioration by 33% (p = 0.002) in females and 16% (p = 0.018) in males with MHO. A 5% reduction in BMI was associated with a 39% and 66% higher chance of MUO resolution in females and males, respectively (both p < 0.001). CONCLUSION The findings support a pathophysiological role of ectopic fat depots in metabolic transitions in obesity and identify female sex as an aggravating factor for adiposity-induced dysmetabolism, which has implications for personalized medicine.
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Affiliation(s)
- Alvaro M Netto
- Faculdade Israelita de Ciências da Saúde Albert Einstein, Rua Comendador Elias Jafet, 755, São Paulo, SP, 05653-000, Brazil
| | - Nea M Kashiwagi
- Hospital Israelita Albert Einstein, Av. Brasil, 1085, São Paulo, SP, 01431-000, Brazil
| | - Carlos A Minanni
- Hospital Israelita Albert Einstein, Av. Brasil, 1085, São Paulo, SP, 01431-000, Brazil
| | - Raul D Santos
- Hospital Israelita Albert Einstein, Av. Brasil, 1085, São Paulo, SP, 01431-000, Brazil; Heart Institute (InCor), University of São Paulo Medical School Hospital, Av. Dr. Enéas Carvalho de Aguiar, 44, São Paulo, SP, 05403-900, Brazil
| | - Fernando Yue Cesena
- Hospital Israelita Albert Einstein, Av. Brasil, 1085, São Paulo, SP, 01431-000, Brazil.
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Ding J, Chen X, Shi Z, Bai K, Shi S. Association of Metabolically Healthy Obesity and Risk of Cardiovascular Disease Among Adults in China: A Retrospective Cohort Study. Diabetes Metab Syndr Obes 2023; 16:151-159. [PMID: 36760599 PMCID: PMC9869897 DOI: 10.2147/dmso.s397243] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 01/10/2023] [Indexed: 01/19/2023] Open
Abstract
PURPOSE Previous studies have shown that metabolically healthy obesity (MHO) and changes in its status are connected to an increased incidence of cardiovascular disease (CVD). Yet, fewer studies have been conducted in China, especially for the middle-aged and elderly population, a high-risk group. The purpose of the study was to investigate the association between metabolic health status and CVD events. PATIENTS AND METHODS A total of 46,055 participants were categorized into 6 subgroups with different metabolic states according to the existence of metabolic syndrome and body mass index (BMI). The changes in obesity and metabolic health status were defined from baseline to follow-up outcomes with a combination of overweight and obesity. Cox proportional hazards models estimated the association of CVD events and each BMI-metabolic groups. RESULTS MHO and metabolic abnormality normal weight (MANW) subjects had a higher HR of CVD, 1.62 (95% CI, 1.36-1.92) and 1.24 (95% CI, 1.07-1.44), respectively, than their metabolically healthy normal weight (MHNW) counterparts. Then, more than 50% and 30% of the metabolically healthy overweight or obesity (MHOO) populations maintained their status and converted to a metabolically unhealthy state, respectively. Stable MANW, MHOO and metabolically abnormal obesity (MAO) were associated with a higher risk for CVD, 1.68 (95% CI, 1.37-2.05),1.26 (95% CI, 1.08-1.47) and 1.65 (95% CI, 1.45-1.88), respectively, than stable MHNW. CONCLUSION Despite being of normal weight, MANW status is in fact a risk factor for CVD, as well as MHO, especially for the Chinese middle-aged and elderly population. Furthermore, metabolic health is a transient state for partial middle-aged and elderly Chinese individuals, and MAO has the highest risk of CVD, including coronary heart disease (CHD) and stroke.
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Affiliation(s)
- Jiacheng Ding
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China
| | - Xuejiao Chen
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China
| | - Zhan Shi
- Department of Pharmacy, Zhengzhou People’s Hospital, Zhengzhou, Henan, People’s Republic of China
| | - Kaizhi Bai
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China
| | - Songhe Shi
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China
- Correspondence: Songhe Shi, Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, No. 100 Science Avenue, Zhengzhou City, Henan Province, People’s Republic of China, Tel + 86 371 18037108985, Email
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Nguedjo MW, Ngondi JL, Ntentie FR, Kingue Azantsa BG, Ntepe Mbah JL, Oben JE. Clinical characteristics and classification of Cameroonians with obesity and metabolically normal phenotype in the West region of Cameroon. Heliyon 2022; 8:e11652. [PMID: 36425423 PMCID: PMC9678690 DOI: 10.1016/j.heliyon.2022.e11652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 07/08/2022] [Accepted: 11/09/2022] [Indexed: 11/19/2022] Open
Abstract
The objective of this study was to classify and suggest an adequate definition of the metabolically normal phenotype among Cameroonians with obesity in the western Region of Cameroon. A cross-sectional study was conducted in the West Cameroon Region from August 2016 to August 2017. A total of 324 subjects with BMI >27 kg/m2, aged of 20 years and older, and not treated for cardiometabolic diseases were included in the study. Sociodemographic and clinical parameters of the subjects were collected. Four definitions of metabolic status were tested to suggest the definition that best identifies the subjects with obesity but metabolically normal phenotype (MNO) in the study. The prevalence of the MNO phenotype varied from 2.50% to 29.60% according to the definitions used. According to the individual definitions, the prevalence of the MNO phenotype was 29.60% according to Hinnouho, 16.00% according to Mbanya, 7.40% according to Meigs and 2.50% according to Widman. Markers of inflammatory profile (high sensitivity C-reactive protein and tumor necrosis factor-alpha), carbohydrate homeostasis (fasting glucose and homeostasis model assessment), markers of lipid profile (total cholesterol and triglyceride), systolic blood pressure, nitric oxide, adiposity indices (Waist circumference and waist to hip ratio) were significantly lower in MNO subjects for the majority of definitions (p < 0.05). The modified Hinnouho definition showed better specificity (60.90%) and sensitivity (12.10%) for an area under the ROC curve of 0.98. The degree of agreement was low between the different pairs of definition of the MNO phenotype (Kappa< 0.61). There is poor agreement between the different definitions of the MNO phenotype among Cameroonians with obesity. Therefore, the adoption of a universal definition of MNO phenotype should be proposed to facilitate the management of metabolic health in people with obesity.
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Affiliation(s)
- Maxwell Wandji Nguedjo
- Department of Biochemistry, Faculty of Sciences, University of Yaounde 1, P. O. Box 812, Yaounde, Cameroon
- Centre for Food, Food Security and Nutrition Research, Institute of Medical Research and Medicinal Plant Studies, P. O. Box 13033, Yaounde, Cameroon
| | - Judith Laure Ngondi
- Department of Biochemistry, Faculty of Sciences, University of Yaounde 1, P. O. Box 812, Yaounde, Cameroon
| | | | - Boris Gabin Kingue Azantsa
- Department of Biochemistry, Faculty of Sciences, University of Yaounde 1, P. O. Box 812, Yaounde, Cameroon
| | - Javeres Leonel Ntepe Mbah
- Laboratory of Human Metabolism and Non-Communicable Disease, Institute of Medical Research and Medicinal Plant Studies, P. O. Box 13033, Yaounde, Cameroon
- Department of Biosciences, COMSATS University Islamabad, Chak Shahzad, Islamabad 45550, Pakistan
| | - Julius Enyong Oben
- Department of Biochemistry, Faculty of Sciences, University of Yaounde 1, P. O. Box 812, Yaounde, Cameroon
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Jahromi MK, Ebadinejad A, Barzin M, Mahdavi M, Niroomand M, Khalili D, Valizadeh M, Azizi F, Hosseinpanah F. Association of cumulative excess weight and waist circumference exposure with transition from metabolically healthy obesity to metabolically unhealthy. Nutr Metab Cardiovasc Dis 2022; 32:2544-2552. [PMID: 36163212 DOI: 10.1016/j.numecd.2022.07.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 07/02/2022] [Accepted: 07/21/2022] [Indexed: 10/31/2022]
Abstract
BACKGROUND AND AIMS The association between obesity severity and duration with the transition from metabolically healthy obese/overweight (MHO) phenotype to metabolically unhealthy obese (MUO) phenotype is not well understood. METHODS AND RESULTS This study includes the Tehran Lipid and Glucose Study participants who were initially classed as MHO. Cumulative excess weight (CEW) and cumulative excess waist circumference (CEWC) scores, which represent the accumulation of body mass index and waist circumference deviations from expected values over time (kg/m2 ∗ y and cm ∗ y, respectively), were calculated until the transition from MHO to MUO or the end of follow-up. The sex-stratified association of CEW and CWEC with the transition from MHO to MUO was investigated by time-dependent Cox models, adjusting for confounders. Out of 2525 participants, 1732 (68.5%) were women. During 15 years of follow-up, 1886 (74.6%) participants transitioned from MHO to MUO. A significant association was found between CEW and CEWC quartiles with the development of MUO among women participants (fully adjusted hazard ratios in the fourth quartile of CEW and CEWC [95% (CI)]:1.65 [1.37-1.98] and [95% CI]: 1.83 [1.53-2.19]). There was no significant association between CEW and CEWC with the MHO transition to MUO among men participants. CONCLUSION Over 15 years of follow-up in TLGS, general and central obesity accumulation was associated with the increased transition from MHO to MUO among women participants. More research with a larger sample size is needed to confirm and explain why the results are different for men and women.
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Affiliation(s)
- Mitra Kazemi Jahromi
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Ebadinejad
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Barzin
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Mahdavi
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahtab Niroomand
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Davood Khalili
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Majid Valizadeh
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farhad Hosseinpanah
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Lei L, Changfa W, Ting Y, Xiaoling Z, Yaqin W. Metabolically healthy transition and its association with body size change patterns among different adult age groups. Diabetes Res Clin Pract 2022; 192:110108. [PMID: 36202384 DOI: 10.1016/j.diabres.2022.110108] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 09/04/2022] [Accepted: 09/23/2022] [Indexed: 11/16/2022]
Abstract
OBJECTIVE To explore the metabolically healthy (MH) to metabolically unhealthy (MU) transition and its association with body size change patterns according to age. METHODS In total, 12,910 MH subjects were evaluated in 2013 and reevaluated in 2020. A MH state was defined as a score ≤ 1, and a MU state was defined as a score > 1 on the National Cholesterol Education Program-Adult Treatment Panel III criteria. RESULTS Approximately 27.0% of MH individuals converted to MU status over the follow-up. Compared with young adults, middle adulthood individuals had a 1.33-fold (95% CI: 1.21-1.46) and late adulthood individuals had a 1.55-fold (95% CI: 1.41-1.70) risk of transition. The body mass index (BMI)/waist circumference (WC)-value change was positively associated with metabolic deterioration; the association weakened with age. With stable normal body size (defined by BMI) as a reference, changing phenotype categories of maximum overweight [hazard ratio (HR): 1.75; 95% CI: 1.56-1.95], non-obesity to general obesity (HR: 2.96; 95% CI: 2.47-3.54) and stable general obesity (HR: 2.44; 95% CI: 1.92-3.10) conferred a higher risk of metabolic deterioration. CONCLUSIONS MH status is a transient state, especially in late and middle adulthood. Individuals transitioning to an obese phenotype should receive attention for concomitant metabolic deterioration.
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Affiliation(s)
- Liu Lei
- Health Management Center, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha, Hunan 410013, China
| | - Wang Changfa
- General Surgery Department, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha, Hunan 410013, China
| | - Yuan Ting
- Health Management Center, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha, Hunan 410013, China
| | - Zhu Xiaoling
- Health Management Center, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha, Hunan 410013, China
| | - Wang Yaqin
- Health Management Center, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha, Hunan 410013, China.
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Khadem A, Shiraseb F, Mirzababaei A, Ghaffarian-Ensaf R, Mirzaei K. Association of Lifelines Diet Score (LLDS) and metabolically unhealthy overweight/obesity phenotypes in women: a cross-sectional study. BMC Womens Health 2022; 22:374. [PMID: 36096807 PMCID: PMC9469615 DOI: 10.1186/s12905-022-01957-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 09/02/2022] [Indexed: 11/22/2022] Open
Abstract
Background Previous studies have shown the association of a number of dietary quality scores with metabolically phenotypes of obesity. Recently, the Lifelines Diet Score (LLDS), which is a fully food-based score based on the 2015 Dutch dietary guidelines and underlying international literature, has been proposed as a tool for assessing the quality of the diet. Therefore, this study was performed to investigate the association between LLDS and metabolically healthy/unhealthy overweight and obesity (MHO/MUHO) phenotypes. Methods This study was performed on 217 women, aged 18–48 years old. For each participant anthropometric values, biochemical test and body composition were evaluated by standard protocols and methods. The LLDS was determined based on 12 components using a valid and reliable food frequency questionnaire (FFQ) containing 147 items. The metabolically healthy (MH) was evaluated using the Karelis criteria. Results Among the total participants in this study, 31.3% of the subjects were MHO while 68.7% were MUHO. After adjustment for potential confounding variables (age, energy intake, and physical activity), participants in highest LLDS tertile had a lower odds of MUHO compared with those in the lowest tertile (OR: 1.18; 95% CI: 0.23, 5.83; P-trend = 0.03). Also, after further adjustment with BMI, provided only small changes in "OR" and did not attenuate the significance (OR: 1.28; 95% CI: 0.23, 6.91; P-trend = 0.02). Conclusions The present evidence indicates that individuals with higher adherence to the LLDS had lower odds of metabolically unhealthy (MUH).
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Association between non-alcoholic fatty liver disease and metabolically healthy deterioration across different body shape phenotypes at baseline and change patterns. Sci Rep 2022; 12:14786. [PMID: 36042236 PMCID: PMC9427771 DOI: 10.1038/s41598-022-18988-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 08/23/2022] [Indexed: 11/29/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome (MetS), and the relationship between NAFLD and metabolic deterioration remains unclear. This study aimed to investigate dynamic changes in metabolically healthy phenotypes and to assess the impact of non-alcoholic fatty liver disease (NAFLD) on the conversion from metabolically healthy (MH) to metabolically unhealthy (MU) phenotypes across body shape phenotypes and phenotypic change patterns. We defined body shape phenotypes using both the body mass index (BMI) and waist circumference (WC) and defined metabolic health as individuals scoring ≤ 1 on the NCEP-ATP III criteria, excluding WC. A total of 12,910 Chinese participants who were MH at baseline were enrolled in 2013 and followed-up in 2019 or 2020. During a median follow-up of 6.9 years, 27.0% (n = 3,486) of the MH individuals developed an MU phenotype. According to the multivariate Cox analyses, NAFLD was a significant predictor of conversion from the MH to MU phenotype, independent of potential confounders (HR: 1.12; 95% confidence interval: 1.02–1.22). For the MH-normal weight group, the relative risk of NAFLD in phenotypic conversion was 1.21 (95% CI 1.03–1.41, P = 0.017), which was relatively higher than that of MH-overweight/obesity group (HR: 1.14, 95% CI 1.02–1.26, P = 0.013). Interestingly, the effect of NAFLD at baseline on MH deterioration was stronger in the “lean” phenotype group than in the “non-lean” phenotype group at baseline and in the “fluctuating non-lean” phenotype change pattern group than in the “stable non-lean” phenotype change pattern group during follow-up. In conclusion, lean NAFLD is not as benign as currently considered and requires more attention during metabolic status screening.
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Karra P, Winn M, Pauleck S, Bulsiewicz-Jacobsen A, Peterson L, Coletta A, Doherty J, Ulrich CM, Summers SA, Gunter M, Hardikar S, Playdon MC. Metabolic dysfunction and obesity-related cancer: Beyond obesity and metabolic syndrome. Obesity (Silver Spring) 2022; 30:1323-1334. [PMID: 35785479 PMCID: PMC9302704 DOI: 10.1002/oby.23444] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 02/24/2022] [Accepted: 03/09/2022] [Indexed: 01/26/2023]
Abstract
OBJECTIVES The metabolic dysfunction driven by obesity, including hyperglycemia and dyslipidemia, increases risk for developing at least 13 cancer types. The concept of "metabolic dysfunction" is often defined by meeting various combinations of criteria for metabolic syndrome. However, the lack of a unified definition of metabolic dysfunction makes it difficult to compare findings across studies. This review summarizes 129 studies that evaluated variable definitions of metabolic dysfunction in relation to obesity-related cancer risk and mortality after a cancer diagnosis. Strategies for metabolic dysfunction management are also discussed. METHODS A comprehensive search of relevant publications in MEDLINE (PubMed) and Google Scholar with review of references was conducted. RESULTS Metabolic dysfunction, defined as metabolic syndrome diagnosis or any number of metabolic syndrome criteria out of clinical range, inflammatory biomarkers, or markers of metabolic organ function, has been associated with risk for, and mortality from, colorectal, pancreatic, postmenopausal breast, and bladder cancers. Metabolic dysfunction associations with breast and colorectal cancer risk have been observed independently of BMI, with increased risk in individuals with metabolically unhealthy normal weight or overweight/obesity compared with metabolically healthy normal weight. CONCLUSION Metabolic dysfunction is a key risk factor for obesity-related cancer, regardless of obesity status. Nonetheless, a harmonized definition of metabolic dysfunction will further clarify the magnitude of the relationship across cancer types, enable better comparisons across studies, and further guide criteria for obesity-related cancer risk stratification.
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Affiliation(s)
- Prasoona Karra
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, Utah, USA
- Cancer Control and Population Sciences Program, Huntsman Cancer Institute, Salt Lake City, Utah, USA
| | - Maci Winn
- Cancer Control and Population Sciences Program, Huntsman Cancer Institute, Salt Lake City, Utah, USA
- Department of Population Health Sciences, School of Medicine, University of Utah, Salt Lake City, Utah, USA
| | - Svenja Pauleck
- Cancer Control and Population Sciences Program, Huntsman Cancer Institute, Salt Lake City, Utah, USA
| | | | - Lacie Peterson
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, Utah, USA
- Cancer Control and Population Sciences Program, Huntsman Cancer Institute, Salt Lake City, Utah, USA
| | - Adriana Coletta
- Cancer Control and Population Sciences Program, Huntsman Cancer Institute, Salt Lake City, Utah, USA
- Department of Health and Kinesiology, University of Utah, Salt Lake City, Utah, USA
| | - Jennifer Doherty
- Cancer Control and Population Sciences Program, Huntsman Cancer Institute, Salt Lake City, Utah, USA
- Department of Population Health Sciences, School of Medicine, University of Utah, Salt Lake City, Utah, USA
| | - Cornelia M. Ulrich
- Cancer Control and Population Sciences Program, Huntsman Cancer Institute, Salt Lake City, Utah, USA
- Department of Population Health Sciences, School of Medicine, University of Utah, Salt Lake City, Utah, USA
| | - Scott A. Summers
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, Utah, USA
| | - Marc Gunter
- Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom
| | - Sheetal Hardikar
- Cancer Control and Population Sciences Program, Huntsman Cancer Institute, Salt Lake City, Utah, USA
- Department of Population Health Sciences, School of Medicine, University of Utah, Salt Lake City, Utah, USA
| | - Mary C. Playdon
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, Utah, USA
- Cancer Control and Population Sciences Program, Huntsman Cancer Institute, Salt Lake City, Utah, USA
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11
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Kim HY, Kim JH. Temporal trends in the prevalence of metabolically healthy overweight and obesity in Korean youth: data from the Korea National Health and Nutrition Examination Survey 2011-2019. Ann Pediatr Endocrinol Metab 2022; 27:134-141. [PMID: 35592898 PMCID: PMC9260377 DOI: 10.6065/apem.2142192.096] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 10/13/2021] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Metabolically healthy overweight/obesity (MHO) and metabolically unhealthy overweight/obesity (MUO) are distinct clinical phenotypes classified by the presence of cardiometabolic risk factors in an individual. In the present study, we investigated temporal trends in the prevalence of MHO in Korean adolescents using nationally representative data. METHODS Data from the Korea National Health and Nutrition Examination Survey 2011-2019 were used in this study. A total of 5,667 adolescents (3,014 boys, 53.2%) aged 10-18 years was included in this study. MHO was defined as a body mass index ≥85th percentile for the corresponding age and sex and absence of any cardiometabolic risk factors. RESULTS The prevalence of overweight/obesity showed an increasing trend from 18.8% (boys 17.3% and girls 20.6%) in 2011 to 23.7% (boys 24.0% and girls 23.5%) in 2019 (p for trend=0.045). The overall prevalence of MHO during 2011-2019 was 39.2%, which was higher in girls than in boys (boys 33.5%, girls 46.2%, p<0.001), and the change in prevalence of MHO from 2011 to 2019 (from 34.8% to 35.7%) was not significant. Among MUO, the most prevalent cardiometabolic risk factor was dysglycemia (48.8%), followed by elevated blood pressure (41.5%), low high-density lipoprotein cholesterol (35.0%), and high triglycerides (29.7%). CONCLUSION We observed a high prevalence of MHO in Korean youth with overweight/obesity. Although the prevalence of overweight/obesity increased, the prevalence of MHO was stable during 2011-2019. A risk-stratified approach based on metabolic health status can help reducing the medical and socioeconomic costs associated with obesity treatment.
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Affiliation(s)
- Hwa Young Kim
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Jae Hyun Kim
- Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea,Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea,Address for correspondence: Jae Hyun Kim Department of Pediatrics, Seoul National Universit y Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam 13620, Korea
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12
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Lin YH, Chang HT, Tseng YH, Chen HS, Chiang SC, Chen TJ, Hwang SJ. Factors related to overweight and obese populations maintaining metabolic health. PeerJ 2022; 10:e13242. [PMID: 35433130 PMCID: PMC9012173 DOI: 10.7717/peerj.13242] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 03/18/2022] [Indexed: 01/13/2023] Open
Abstract
Background For people who are overweight or obese, maintaining a metabolically healthy status can decrease the risks of developing cardiovascular diseases and Type 2 diabetes. Despite this, only a limited amount of research has discussed the metabolically healthy overweight and obesity (MHOO) population in Asia and the factors associated with them maintaining their metabolic health. Methods This study enrolled 195 MHOO participants from communities in northern Taiwan during 2009-2010 (baseline). Of the 195 participants, 89 completed the follow-up assessment after a median follow-up time of nine years. Body type was determined by body mass index (BMI, kg/m2). We defined overweight as a BMI ≥ 24 kg/m2 and <27 kg/m2 and defined obese as a BMI ≥ 27 kg/m2. Metabolic health was defined as the absence of cardiometabolic diseases and the presence of ≤1 of the cardiometabolic risk factors, namely hypertension, hyperglycemia, hypertriglyceridemia, and low serum high-density lipoprotein cholesterol. Metabolic health, BMI, and other covariates were evaluated at both baseline and follow-up. Generalized estimating equations (GEE) models were used to analyze the factors associated with maintenance of metabolic health during the follow-up period. Results At baseline, the mean age of the study participants was 47.4 (SD 5.3) years and 46 (51.7%) of the participants were women. There were 51 (57.3%) individuals who maintained their metabolic health status at the time of the nine-year follow-up. The detrimental factors pertaining to metabolic health included older age, longer duration until follow-up, BMI ≥ 27 kg/m2, and increase in waist circumference. No significant relationships were observed between sociodemographic factors and lifestyle factors, such as sex, level of education, cigarette smoking, alcohol consumption, and physical activity, and sustained metabolic health among MHOO individuals. Conclusions To maintain metabolic health and prevent negative changes in health status, control of bodyweight and waist circumference should remain a priority for MHOO individuals even when there are no metabolic disorders present.
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Affiliation(s)
- Yi-Hsuan Lin
- Department of Family Medicine, Cheng Hsin General Hospital, Taipei, Taiwan,Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Hsiao-Ting Chang
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yen-Han Tseng
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Harn-Shen Chen
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shu-Chiung Chiang
- Institute of Hospital and Health Care Administration, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Tzeng-Ji Chen
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan,Institute of Hospital and Health Care Administration, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Shinn-Jang Hwang
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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13
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Malnutrition and Biomarkers: A Journey through Extracellular Vesicles. Nutrients 2022; 14:nu14051002. [PMID: 35267977 PMCID: PMC8912428 DOI: 10.3390/nu14051002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 02/24/2022] [Accepted: 02/25/2022] [Indexed: 02/04/2023] Open
Abstract
Extracellular vesicles (EVs) have been identified as active components in cellular communication, which are easily altered both morphologically and chemically by the cellular environment and metabolic state of the body. Due to this sensitivity to the conditions of the cellular microenvironment, EVs have been found to be associated with disease conditions, including those associated with obesity and undernutrition. The sensitivity that EVs show to changes in the cellular microenvironment could be a reflection of early cellular alterations related to conditions of malnutrition, which could eventually be used in the routine monitoring and control of diseases or complications associated with it. However, little is known about the influence of malnutrition alone; that is, without the influence of additional diseases on the heterogeneity and specific content of EVs. To date, studies in “apparently healthy” obese patients show that there are changes in the size, quantity, and content of EVs, as well as correlations with some metabolic parameters (glucose, insulin, and serum lipids) in comparison with non-obese individuals. In light of these changes, a direct participation of EVs in the development of metabolic and cardiovascular complications in obese subjects is thought to exist. However, the mechanisms through which this process might occur are not yet fully understood. The evidence on EVs in conditions of undernutrition is limited, but it suggests that EVs play a role in the maintenance of homeostasis and muscle repair. A better understanding of how EVs participate in or promote cellular signaling in malnutrition conditions could help in the development of new strategies to treat them and their comorbidities.
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14
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Corrales P, Vidal-Puig A, Medina-Gómez G. Obesity and pregnancy, the perfect metabolic storm. Eur J Clin Nutr 2021; 75:1723-1734. [PMID: 33911209 DOI: 10.1038/s41430-021-00914-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 03/15/2021] [Accepted: 03/29/2021] [Indexed: 02/02/2023]
Abstract
Pregnancy is a physiological stress that requires dynamic, regulated changes affecting maternal and fetal adiposity. Excessive accumulation of dysfunctional adipose tissue defined by metabolic and molecular alterations cause severe health consequences for mother and fetus. When subjected to sustained overnutrition, the cellular and lipid composition of the adipose tissue changes predisposing to insulin resistance, diabetes, and other metabolic disorders compromising the outcome of the pregnancy. Moreover, excessive maternal weight gain, usually in the context of obesity, predisposes to an increased flux of nutrients from mother to fetus throughout the placenta. The fetus of an obese mother will accumulate more adiposity and may increase the risk of future metabolic disorder later in life. Thus, further understanding of the interaction between maternal metabolism, epigenetic regulation of the adipose tissue, and their transgenerational transfer are required to mitigate the adverse health outcomes for the mother and the fetus associated with maternal obesity.
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Affiliation(s)
- Patricia Corrales
- Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain.
| | - Antonio Vidal-Puig
- Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
- Wellcome Trust Sanger Institute, Hinxton, UK
- Cambridge University Nanjing Centre of Technology and Innovation, Nanjing, PR China
| | - Gema Medina-Gómez
- Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain.
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15
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Tutunchi H, Naeini F, Ebrahimi-Mameghani M, Najafipour F, Mobasseri M, Ostadrahimi A. Metabolically healthy and unhealthy obesity and the progression of liver fibrosis: A cross-sectional study. Clin Res Hepatol Gastroenterol 2021; 45:101754. [PMID: 34303827 DOI: 10.1016/j.clinre.2021.101754] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 06/22/2021] [Accepted: 06/23/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND The development of liver fibrosis is the most important predictor of adverse outcomes in patients with non-alcoholic fatty liver disease (NAFLD). Little is known regarding the risk factors for the progression of NAFLD to liver fibrosis. The present cross-sectional study aimed to examine the association of liver fibrosis with metabolically healthy and unhealthy obesity among patients with NAFLD. METHODS The severity of fatty liver was examined using ultrasonography. We used the NAFLD fibrosis score to determine the severity of liver fibrosis. Anthropometric indices, physical activity, and body composition were assessed. Blood samples were collected to determine serum metabolic parameters. Participants without any component of metabolic syndrome and homeostasis model assessment of insulin resistance (HOMA-IR) <2.5 were considered as metabolically healthy. To examine the association of liver fibrosis with metabolically healthy and unhealthy obesity, multivariable-adjusted odds ratios (ORs) were applied. RESULTS The current study included a total of 246 patients with NAFLD and low probability of fibrosis. 46.3% of subjects were metabolically healthy and 53.7% were metabolically unhealthy. Among metabolically healthy subjects, multivariable-adjusted ORs (CIs) for worsening of NAFLD fibrosis score comparing body mass indexes (BMIs) 23.0-24.9, 25-29.9, and ≥30 with a BMI=18.5-22.9 kg/m2 were 1.28 (1.09-1.56), 1.99 (1.49-2.63), and 3.96 (2.89-4.71), respectively. The corresponding ORs (95% CIs) among metabolically unhealthy subjects were 1.39 (1.32-1.64), 2.27 (1.98-2.49), and 4.11 (3.12-4.93), respectively. Moreover, in both healthy and unhealthy individuals, higher percentages of body fat and waist circumference were significantly associated with worsening of NAFLD fibrosis score. CONCLUSION Excess body fat contributes to the progression of liver fibrosis regardless of metabolic health status.
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Affiliation(s)
- Helda Tutunchi
- Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Naeini
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran university of medical science, Tehran, Iran
| | - Mehrangiz Ebrahimi-Mameghani
- Social Determinant of Health Research Center, School of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farzad Najafipour
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Majid Mobasseri
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Ostadrahimi
- Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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16
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Santos D, Carvalho E. Adipose-related microRNAs as modulators of the cardiovascular system: the role of epicardial adipose tissue. J Physiol 2021; 600:1171-1187. [PMID: 34455587 DOI: 10.1113/jp280917] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 08/24/2021] [Indexed: 11/08/2022] Open
Abstract
Adipose tissue expansion and subsequent metabolic dysfunction has been considered one of the major risk factors for development of cardiometabolic disease. Epicardial adipose tissue (EAT) in particular is a unique subtype of visceral adipose tissue located on the surface of the heart, around the coronary arteries. Due to its proximity, EAT can modulate the local metabolic and immune function of cardiomyocytes and coronary arteries. Several microRNAs have been described as key players in both cardiac and vascular function that when dysregulated will contribute to dysfunction. Here we review the influence of obesity in the crosstalk between specific adipose tissue types, in particular the EAT-secreted microRNAs, as key modulators of cardiac disease progression, not only as early biomarkers but also as therapeutic targets for cardiometabolic disease.
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Affiliation(s)
- Diana Santos
- PhD Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal.,Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.,Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal
| | - Eugenia Carvalho
- Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.,Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal.,Portuguese Diabetes Association (APDP), Lisbon, Portugal
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17
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Rohner M, Heiz R, Feldhaus S, Bornstein SR. Hepatic-Metabolite-Based Intermittent Fasting Enables a Sustained Reduction in Insulin Resistance in Type 2 Diabetes and Metabolic Syndrome. Horm Metab Res 2021; 53:529-540. [PMID: 34192792 PMCID: PMC8360708 DOI: 10.1055/a-1510-8896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 05/12/2021] [Indexed: 11/03/2022]
Abstract
Insulin resistance is the hallmark of Type 2 Diabetes and is still an unmet medical need. Insulin resistance lies at the crossroads of non-alcoholic fatty liver disease, obesity, weight loss and exercise resistance, heart disease, stroke, depression, and brain health. Insulin resistance is purely nutrition related, with a typical molecular disease food intake pattern. The insulin resistant state is accessible by TyG as the appropriate surrogate marker, which is found to lead the personalized molecular hepatic nutrition system for highly efficient insulin resistance remission. Treating insulin resistance with a molecular nutrition-centered approach shifts the treatment paradigm of Type 2 Diabetes from management to cure. This allows remission within five months, with a high efficiency rate of 85%. With molecular intermittent fasting a very efficient treatment for prediabetes and metabolic syndrome is possible, improving the non-alcoholic fatty liver disease (NAFL) state and enabling the body to lose weight in a sustainable manner.
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Affiliation(s)
| | - Robert Heiz
- Zentrum für Komplementärmedizin AG, Uster,
Switzerland
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18
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Elías-López D, Vargas-Vázquez A, Mehta R, Cruz Bautista I, Del Razo Olvera F, Gómez-Velasco D, Almeda Valdes P, Aguilar-Salinas CA. Natural course of metabolically healthy phenotype and risk of developing Cardiometabolic diseases: a three years follow-up study. BMC Endocr Disord 2021; 21:85. [PMID: 33910543 PMCID: PMC8080399 DOI: 10.1186/s12902-021-00754-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 04/19/2021] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Whether the metabolically healthy obese (MHO) phenotype is a single, stable or a transitional, fluctuating state is currently unknown. The Mexican-Mestizo population has a genetic predisposition for the development of type 2 diabetes (T2D) and other cardiometabolic complications. Little is known about the natural history of metabolic health in this population. The aim of this study was to analyze the transitions over time among individuals with different degrees of metabolic health and body mass index, and evaluate the incidence of cardiometabolic outcomes according to phenotype. METHODS The study population consisted of a metabolic syndrome cohort with at least 3 years of follow up. Participants were apparently-healthy urban Mexican adults ≥20 years with a body mass index (BMI) ≥20 kg/m2. Metabolically healthy phenotype was defined using the criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) metabolic syndrome criteria and the subjects were stratified into 4 groups according to their BMI and metabolic health. For cardiometabolic outcomes we estimated the incidence of cardiometabolic outcomes and standardized them per 1, 000 person-years of follow-up. Finally, to evaluate the risk for transition and development of cardiometabolic outcomes, we fitted Cox Proportional Hazard regression models. RESULTS Amongst the 5541 subjects, 54.2% were classified as metabolically healthy and 45.8% as unhealthy. The MHO prevalence was 39.3%. Up to a third of the population changed from their initial category to another and the higher transition rate was observed in MHO (42.9%). We also found several novel factors associated to transition to metabolically unhealthy phenotype; socioeconomic status, number of pregnancies, a high carbohydrate intake, history of obesity and consumption of sweetened beverages. Similarly, visceral adipose tissue (VAT) was a main predictor of transition; loss of VAT ≥5% was associated with reversion from metabolically unhealthy to metabolically healthy phenotype (hazard ratio (HR) 1.545, 95%CI 1.266-1.886). Finally, we observed higher incidence rates and risk of incident T2D and hypertension in the metabolically unhealthy obesity (MUHO) and metabolically unhealthy lean (MUHL) phenotypes compared to MHO. CONCLUSIONS Metabolic health is a dynamic and continuous process, at high risk of transition to metabolically unhealthy phenotypes over time. It is imperative to establish effective processes in primary care to prevent such transitions.
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Affiliation(s)
- Daniel Elías-López
- Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. CP 14080; Tlalpan, México City, Mexico
- Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Arsenio Vargas-Vázquez
- Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. CP 14080; Tlalpan, México City, Mexico
- MD/PhD (PECEM) Program, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | - Roopa Mehta
- Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. CP 14080; Tlalpan, México City, Mexico
- Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Ivette Cruz Bautista
- Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. CP 14080; Tlalpan, México City, Mexico
| | - Fabiola Del Razo Olvera
- Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. CP 14080; Tlalpan, México City, Mexico
| | - Donaji Gómez-Velasco
- Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. CP 14080; Tlalpan, México City, Mexico
| | - Paloma Almeda Valdes
- Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. CP 14080; Tlalpan, México City, Mexico
- Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | - Carlos A Aguilar-Salinas
- Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. CP 14080; Tlalpan, México City, Mexico.
- Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México.
- Instituto Tecnologico y de Estudios Superiores de Monterrey Tec Salud, México City, México.
- División de Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
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Gómez-Zorita S, Queralt M, Vicente MA, González M, Portillo MP. Metabolically healthy obesity and metabolically obese normal weight: a review. J Physiol Biochem 2021; 77:175-189. [PMID: 33704694 DOI: 10.1007/s13105-020-00781-x] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 12/23/2020] [Indexed: 02/07/2023]
Abstract
Despite the general relationship between obesity and its co-morbidities, there are both obese individuals who scarcely present the associated pathologies (metabolically healthy obese; MHO) and individuals who present obesity alterations despite having normal weight (metabolically obese normal weight; MONW). It is still difficult to define metabolically MHO and MONW individuals because different classifications have been used in the studies reported. Indeed, different inclusion criteria have been used to discriminate between metabolically healthy and metabolically unhealthy subjects. Due to this and other reasons, such as differences in ethnicity, genetics, and lifestyle of the populations, data concerning the prevalence of MHO and MONW are very variable. The main determinants of MHO are type of growth (hypertrophy or hyperplasia), anatomical location, inflammation of adipose tissue, ectopic fat accumulation, genetic factors, and lifestyles factors. In the case of MONW, the main determinants are genetic background and lifestyle factors. With regard to treatment, it is not clear whether MHO subjects would benefit from traditional lifestyle interventions, based on diet energy restriction and increased physical activity. For MONW subjects, there is still no specialized treatment, and the therapies are the same as those used in obese subjects.
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Affiliation(s)
- Saioa Gómez-Zorita
- Nutrition and Obesity Group. Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Institute, Vitoria, Spain. .,BIOARABA Health Research Institute, Vitoria, Spain. .,CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Vitoria, Spain.
| | - Maite Queralt
- Nutrition and Obesity Group. Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Institute, Vitoria, Spain
| | - Maria Angeles Vicente
- BIOARABA Health Research Institute, Vitoria, Spain.,Alava University Hospital (Osakidetza), Vitoria, Spain
| | - Marcela González
- Nutrition and Food Science Department, Faculty of Biochemistry and Biological Sciences, National University of Litoral and National Scientific and Technical Research Council (CONICET), 3000, Santa Fe, Argentina
| | - María P Portillo
- Nutrition and Obesity Group. Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Institute, Vitoria, Spain.,BIOARABA Health Research Institute, Vitoria, Spain.,CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Vitoria, Spain
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20
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Min J, Hu X, Zhang J, Zeng T, Wang Y, Tian S, Liu G, Zhong X, Qiu K, Peng M, Chen L. Short-Term Changes in Metabolically Healthy Overweight/Obesity Status Impact the Susceptibility to Type 2 Diabetes in Chinese Adults. Diabetes Metab Syndr Obes 2021; 14:2561-2571. [PMID: 34135608 PMCID: PMC8200172 DOI: 10.2147/dmso.s313475] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 05/27/2021] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Changes in transition from metabolically healthy overweight/obesity (MHO) to metabolically unhealthy overweight/obesity (MUO) are associated with the risk for cardiometabolic complications. This study aims to investigate the effects of short-term dynamic changes in body mass index (BMI) and metabolic status on the risk of type 2 diabetes (T2D) and to identify biological predictors for the MHO-to-MUO transition. PATIENTS AND METHODS A total of 4604 subjects from the REACTION study were included for a 3-year follow-up. Subjects were categorized based on their BMI and metabolic syndrome status. Overweight/obesity was defined as BMI ≥ 24 kg/m2. Metabolically healthy was defined as having two or fewer of the metabolic syndrome components proposed by the Chinese Diabetes Society. Thus, subjects were divided into four groups: metabolically healthy normal weight (MHNW), MHO, metabolically unhealthy normal weight (MUNW), and MUO. RESULTS Compared with MHNW, MHO was not predisposed to an increased risk for T2D (OR 1.08, 95% CI 0.64-1.83, P = 0.762). However, a 3-year transition probability of 20.6% was identified for subjects who shifted from MHO to MUO; this conversion increased the risk of T2D by 3-fold (OR 3.04, 95% CI 1.21-7.68, P = 0.018). The fatty liver index independently predicted the MHO-to-MUO transition with an OR 3.14 (95% CI 1.56-7.46, P = 0.002) when comparing the fourth quartile to the first quartile. CONCLUSION This study reveals that metabolic changes affect the short-term susceptibility to T2D in the overweight/obese Chinese population, and the fatty liver index is an efficient clinical parameter for identifying those with a metabolic deterioration risk.
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Affiliation(s)
- Jie Min
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Xiang Hu
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Jiaoyue Zhang
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Tianshu Zeng
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Ying Wang
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Shenghua Tian
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Geng Liu
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Xueyu Zhong
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Kangli Qiu
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Miaomiao Peng
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Lulu Chen
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
- Correspondence: Lulu Chen Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, People’s Republic of ChinaTel +86 27 8572 6082Fax +86 27 8535 6365 Email
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21
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Burton-Pimentel KJ, Pimentel G, Hughes M, Michielsen CC, Fatima A, Vionnet N, Afman LA, Roche HM, Brennan L, Ibberson M, Vergères G. Discriminating Dietary Responses by Combining Transcriptomics and Metabolomics Data in Nutrition Intervention Studies. Mol Nutr Food Res 2020; 65:e2000647. [PMID: 33325641 PMCID: PMC8221028 DOI: 10.1002/mnfr.202000647] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 11/03/2020] [Indexed: 12/17/2022]
Abstract
Scope Combining different “omics” data types in a single, integrated analysis may better characterize the effects of diet on human health. Methods and results The performance of two data integration tools, similarity network fusion tool (SNFtool) and Data Integration Analysis for Biomarker discovery using Latent variable approaches for “Omics” (DIABLO; MixOmics), in discriminating responses to diet and metabolic phenotypes is investigated by combining transcriptomics and metabolomics datasets from three human intervention studies: a postprandial crossover study testing dairy foods (n = 7; study 1), a postprandial challenge study comparing obese and non‐obese subjects (n = 13; study 2); and an 8‐week parallel intervention study that assessed three diets with variable lipid content on fasting parameters (n = 39; study 3). In study 1, combining datasets using SNF or DIABLO significantly improve sample classification. For studies 2 and 3, the value of SNF integration depends on the dietary groups being compared, while DIABLO discriminates samples well but does not perform better than transcriptomic data alone. Conclusion The integration of associated “omics” datasets can help clarify the subtle signals observed in nutritional interventions. The performance of each integration tool is differently influenced by study design, size of the datasets, and sample size.
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Affiliation(s)
- Kathryn J Burton-Pimentel
- Federal Department of Economic Affairs, Education and Research EAER, Agroscope, Schwarzenburgstrasse 161, Bern, 3003, Switzerland
| | - Grégory Pimentel
- Federal Department of Economic Affairs, Education and Research EAER, Agroscope, Schwarzenburgstrasse 161, Bern, 3003, Switzerland
| | - Maria Hughes
- UCD Institute of Food and Health, School of Public Health, Physiotherapy, and Sports Science, University College Dublin, Belfield, Dublin 4, D04 C7X2, Ireland.,Diabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Research, Belfield, Dublin 4, Ireland.,Nutrigenomics Research Group, UCD Conway Institute and UCD Institute of Food and Health, School of Public Health, Physiotherapy and Sports Science, Belfield, Dublin 4, D04 V1W8, Ireland
| | - Charlotte Cjr Michielsen
- Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University and Research, P.O. Box 17, Wageningen, 6700 AA, The Netherlands
| | - Attia Fatima
- UCD Institute of Food and Health, School of Public Health, Physiotherapy, and Sports Science, University College Dublin, Belfield, Dublin 4, D04 C7X2, Ireland.,Nutrigenomics Research Group, UCD Conway Institute and UCD Institute of Food and Health, School of Public Health, Physiotherapy and Sports Science, Belfield, Dublin 4, D04 V1W8, Ireland
| | - Nathalie Vionnet
- Service of Endocrinology, Diabetes and Metabolism, Lausanne University Hospital, Lausanne, 1011, Switzerland
| | - Lydia A Afman
- Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University and Research, P.O. Box 17, Wageningen, 6700 AA, The Netherlands
| | - Helen M Roche
- UCD Institute of Food and Health, School of Public Health, Physiotherapy, and Sports Science, University College Dublin, Belfield, Dublin 4, D04 C7X2, Ireland.,Diabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Research, Belfield, Dublin 4, Ireland.,Nutrigenomics Research Group, UCD Conway Institute and UCD Institute of Food and Health, School of Public Health, Physiotherapy and Sports Science, Belfield, Dublin 4, D04 V1W8, Ireland.,Institute for Global Food Security, Queens University Belfast, Belfast, BT7 1NN, United Kingdom
| | - Lorraine Brennan
- UCD Institute of Food & Health, School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, D04 V1W8, Ireland
| | - Mark Ibberson
- Vital IT, Quartier UNIL-Sorge, Lausanne, 1015, Switzerland.,Swiss Institute of Bioinformatics, Quartier UNIL-Sorge, Lausanne, 1015, Switzerland
| | - Guy Vergères
- Federal Department of Economic Affairs, Education and Research EAER, Agroscope, Schwarzenburgstrasse 161, Bern, 3003, Switzerland
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22
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Lundqvist S, Börjesson M, Cider Å, Hagberg L, Ottehall CB, Sjöström J, Larsson MEH. Long-term physical activity on prescription intervention for patients with insufficient physical activity level-a randomized controlled trial. Trials 2020; 21:793. [PMID: 32933577 PMCID: PMC7493144 DOI: 10.1186/s13063-020-04727-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 09/06/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Physical activity (PA) can be used to prevent and treat diseases. In Sweden, licensed healthcare professionals use PA on prescription (PAP) to support patients to increase their PA level. The aim of this randomized controlled trial was to evaluate a 2-year intervention of two different strategies of PAP treatment for patients with insufficient PA level, after a previous 6-month period of ordinary PAP treatment in a primary health care setting. METHODS We included 190 patients, 27-77 years, physically inactive with metabolic risk factors where the patients were not responding to a previous 6-month PAP treatment with increased PA. The patients were randomized to either enhanced support from a physiotherapist (PT group) or continued ordinary PAP treatment at the health care centre (HCC group). The PAP treatment included an individualized dialogue; an individually dosed PA recommendation, including a written prescription; and a structured follow-up. In addition to PAP, the PT group received aerobic fitness tests and more frequent scheduled follow-ups. The patient PA level, metabolic health, and health-related quality of life (HRQOL) were measured at baseline and at 1- and 2-year follow-ups. RESULTS At the 2-year follow-up, 62.9% of the PT group and 50.8% of the HCC group had increased their PA level and 31.4% vs. 38.5% achieved ≥ 150 min of moderate-intensity PA/week (difference between groups n.s.). Over 2 years, both groups displayed increased high-density lipoproteins (HDL) (p = 0.004 vs. baseline), increased mental health status (MCS) (p = 0.036), and reduced body mass index (BMI) (p = 0.001), with no difference between groups. CONCLUSION During long-term PAP interventions, the PA level, metabolic health, and HRQOL increased in patients at metabolic risk without significant differences between groups. The results indicate to be independent of any changes in pharmacological treatment. We demonstrated that the PAP treatment was feasible in ordinary primary care. Both the patients and the healthcare system benefitted from the improvement in metabolic risk factors. Future studies should elucidate effective long-term PAP-treatment strategies. TRIAL REGISTRATION ClinicalTrials.gov NCT03012516 . Registered on 30 December 2016-retrospectively registered.
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Affiliation(s)
- Stefan Lundqvist
- Department of Health and Rehabilitation, Unit of Physiotherapy, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. .,Centrum för fysisk aktivitet Göteborg, Gothenburg, Region Västra Götaland, Sweden.
| | - Mats Börjesson
- Center for Health and Performance (CHP), University of Gothenburg, Gothenburg, Sweden.,Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Sahlgrenska University Hospital/Östra, Gothenburg, Region Västra Götaland, Sweden
| | - Åsa Cider
- Department of Health and Rehabilitation, Unit of Physiotherapy, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lars Hagberg
- University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | | | - Johan Sjöström
- Centrum för fysisk aktivitet Göteborg, Gothenburg, Region Västra Götaland, Sweden
| | - Maria E H Larsson
- Department of Health and Rehabilitation, Unit of Physiotherapy, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Research and Development Primary Health Care, Gothenburg, Region Västra Götaland, Sweden
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23
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Genetic markers and continuity of healthy metabolic status: Tehran cardio-metabolic genetic study (TCGS). Sci Rep 2020; 10:13600. [PMID: 32788640 PMCID: PMC7423921 DOI: 10.1038/s41598-020-70627-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 07/23/2020] [Indexed: 12/29/2022] Open
Abstract
Obese individuals can be categorized as “healthy obese” (MHO) and “unhealthy obese” (MUO) based on the presence or absence of metabolic abnormality. This study sets out to assess potential genetic causes behind persistence of healthy metabolic status in individuals categorized as “healthy obese”. This study was conducted in the framework of the Tehran cardio-metabolic genetic study (TCGS). 766 MHO subjects at the start of the study followed up 15 years for occurrence of metabolic unhealthy status. These two groups (persistent MHO, MUO) were compared regarding the presence or absence of 16 single nucleotide polymorphisms (SNPs) identified as being associated with obesity phenotype in previous studies. We used logistic regression model for assessing the association between MHO/MUO with candidate SNPs. By the end of the follow up, 206 (27%) were categorized as the persistent MHO and 560 (73%) as MUO groups. Considering interaction effect between some SNP and sex, a sex stratification analysis was applied. When the analysis was performed by gender, rs1121980 associated with a decrease, and rs7903146 with an increase in the likelihood of persistent MHO individuals. Another analysis was separately performed on postmenopausal women from both groups; it showed that rs13107325 was associated with an increase in the likelihood of persistent MHO status in this subgroup of woman. In all cases, the markers had dominant inheritance. This findings suggest that the expression of some genetic markers are associated with persistence of healthy metabolic status, in female obese individuals.
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24
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Perrone MA, Babu Dasari J, Intorcia A, Gualtieri P, Marche M, Di Luozzo M, Merra G, Bernardini S, Romeo F, Sergi D. Phenotypic classification and biochemical profile of obesity for cardiovascular prevention. GAZZETTA MEDICA ITALIANA ARCHIVIO PER LE SCIENZE MEDICHE 2020. [DOI: 10.23736/s0393-3660.20.04259-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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25
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Smith GI, Mittendorfer B, Klein S. Metabolically healthy obesity: facts and fantasies. J Clin Invest 2020; 129:3978-3989. [PMID: 31524630 DOI: 10.1172/jci129186] [Citation(s) in RCA: 378] [Impact Index Per Article: 75.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
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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Abstract
PURPOSE OF REVIEW To present a comprehensive overview regarding criteria, epidemiology, and controversies that have arisen in the literature about the existence and the natural course of the metabolic healthy phenotype. RECENT FINDINGS The concept of metabolically healthy obesity (MHO) implies that a subgroup of obese individuals may be free of the cardio-metabolic risk factors that commonly accompany obese subjects with adipose tissue dysfunction and insulin resistance, known as having metabolic syndrome or the metabolically unhealthy obesity (MUO) phenotype. Individuals with MHO appear to have a better adipose tissue function, and are more insulin sensitive, emphasizing the central role of adipose tissue function in metabolic health. The reported prevalence of MHO varies widely, and this is likely due the lack of universally accepted criteria for the definition of metabolic health and obesity. Also, the natural course and the prognostic value of MHO is hotly debated but it appears that it likely evolves towards MUO, carrying an increased risk for cardiovascular disease and mortality over time. Understanding the pathophysiology and the determinants of metabolic health in obesity will allow a better definition of the MHO phenotype. Furthermore, stratification of obese subjects, based on metabolic health status, will be useful to identify high-risk individuals or subgroups and to optimize prevention and treatment strategies to compact cardio-metabolic diseases.
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Affiliation(s)
- Agathocles Tsatsoulis
- Department of Endocrinology, School of Health Sciences, University of Ioannina, 451 10, Ioannina, Greece.
| | - Stavroula A Paschou
- Division of Endocrinology and Diabetes, "Aghia Sophia" Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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27
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Abstract
A peculiar category of persons with obesity lacking common metabolic disturbances has been depicted and termed as metabolically healthy obesity (MHO). Yet, although MHO patients are free of obesity-associated complications, they might not be entirely precluded from developing cardio-metabolic disorders. Among patients with morbid obesity (MO) who are referred to bariatric surgery, a subset of metabolically healthy MO (MHMO) has been identified and the question arises if these patients would benefit from surgery in terms of mitigating the peril of cardio-metabolic complications. We revisited the pathophysiological mechanisms that define MHO, the currently available data on the cardio-metabolic risk of these patients and finally we reviewed the benefits of bariatric surgery and the urge to better characterize MHMO before submission to surgery.
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Affiliation(s)
- Adriana Florinela Cătoi
- Pathophysiology Department, Faculty of Medicine, 'Iuliu Hațieganu', University of Medicine and Pharmacy Cluj-Napoca Romania, Cluj-Napoca, Romania.
| | - Luca Busetto
- Department of Medicine, University of Padova, Padua, Italy
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28
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Jeske M. Constructing complexity: collective action framing and rise of obesity research. BIOSOCIETIES 2020. [DOI: 10.1057/s41292-020-00182-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Abstract
The last few decades have witnessed a global rise in the number of older individuals. Despite this demographic shift, morbidity within this population group is high. Many factors influence healthspan; however, an obesity pandemic is emerging as a significant determinant of older people's health. It is well established that obesity adversely affects several metabolic systems. However, due to its close association with overall cardiometabolic health, the impact that obesity has on cholesterol metabolism needs to be recognised. The aim of the present review is to critically discuss the effects that obesity has on cholesterol metabolism and to reveal its significance for healthy ageing.
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30
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Camhi SM, Must A, Gona PN, Hankinson A, Odegaard A, Reis J, Gunderson EP, Jacobs DR, Carnethon MR. Duration and stability of metabolically healthy obesity over 30 years. Int J Obes (Lond) 2019; 43:1803-1810. [PMID: 30158567 PMCID: PMC6395568 DOI: 10.1038/s41366-018-0197-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 07/19/2018] [Accepted: 07/30/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Obese adults who are free from metabolic risk factors may develop risk factors over time. Our objective was to characterize development of obesity and duration of metabolically healthy obese (MHO) over 30 years. METHODS Participants in CARDIA who developed obesity (BMI ≥ 30 kg/m2) at follow-up exams during years 7, 10, 15, 20, 25, and 30 were analyzed. MHO was defined as obese and having 0 or 1 risk factor: ≥SBP/DBP 130/85 mmHg; fasting glucose ≥100 mg/dL/5.55 mmol/L; fasting triglycerides (≥150 mg/dL/1.69 mmol/L); and HDL-C (men <40 mg/dL/1.036 mmol/L, women <50 mg/dL/1.295 mmol/L) or on any medication(s) for these conditions. MHO duration (years) and obesity duration (years) were estimated for each subsequent time-point; and an overall cumulative duration was also calculated over available follow-up. MHO duration (%) was approximated as MHO duration ÷ obesity duration. Stable MHO was defined as 100% MHO duration over follow-up, while transient MHO was defined as <1-99%. Chi-squared tests were used to compare proportions by sex and race across obesity phenotypes. Multivariable-adjusted ANCOVA, adjusting for baseline BMI, age, race, and sex, was used to analyze obesity duration in all individuals who developed obesity, and also compare MHO duration (%) across race and sex in transient MHO individuals. RESULTS Of the 987 eligible participants who developed obesity, 51% were African American (AA), 56% were women. Higher percentages of AA were classified as transient MHO, and higher proportions of females were MHO (both p < 0.0001). Obesity duration (years) was higher in transient MHO compared with stable MHO (mean difference: 6.2 ± 0.5 years, p < 0.0001). Of those with transient MHO, African Americans (51.4 ± 1.6%) were more likely to have longer MHO duration compared to Caucasians (44.4 ± 1.9%, p = 0.005). CONCLUSION MHO status can be a transient phenotype which differs by sex and race. Future studies are needed to explore modifiable lifestyle/behavioral predictors associated with longer MHO duration.
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Affiliation(s)
| | | | | | | | | | - Jared Reis
- National Heart, Lung, and Blood Institute at the National Institutes of Health, Bethesda, MD, USA
| | - Erica P Gunderson
- Cardiovascular and Metabolic Conditions Section, Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
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Remor JM, Lopes WA, Locateli JC, Oliveira RP, Simões CF, Barrero CAL, Nardo Jr N. Prevalence of metabolically healthy obese phenotype and associated factors in South American overweight adolescents: A cross-sectional study. Nutrition 2019; 60:19-24. [DOI: 10.1016/j.nut.2018.08.017] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 07/16/2018] [Accepted: 08/22/2018] [Indexed: 12/29/2022]
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Abstract
Cardiovascular complications are commonly associated with obesity. However, a subgroup of obese individuals may not be at an increased risk for cardiovascular complications; these individuals are said to have metabolically healthy obesity (MHO). In contrast, metabolically unhealthy individuals are at high risk of cardiovascular disease (CVD), irrespective of BMI; thus, this group can include individuals within the normal weight category (BMI 18.5-24.9 kg/m2). This review provides a summary of prospective studies on MHO and metabolically unhealthy normal-weight (MUHNW) phenotypes. Notably, there is ongoing dispute surrounding the concept of MHO, including the lack of a uniform definition and the potentially transient nature of metabolic health status. This review highlights the relevance of alternative measures of body fatness, specifically measures of fat distribution, for determining MHO and MUHNW. It also highlights alternative approaches of risk stratification, which account for the continuum of risk in relation to CVD, which is observable for most risk factors. Moreover, studies evaluating the transition from metabolically healthy to unhealthy phenotypes and potential determinants for such conversions are discussed. Finally, the review proposes several strategies for the use of epidemiological research to further inform the current debate on metabolic health and its determination across different stages of body fatness.
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Affiliation(s)
- Matthias B Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
- Institute of Nutritional Sciences, University of Potsdam, Nuthetal, Germany.
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Lee MJ, Kim EH, Bae SJ, Choe J, Jung CH, Lee WJ, Kim HK. Protective role of skeletal muscle mass against progression from metabolically healthy to unhealthy phenotype. Clin Endocrinol (Oxf) 2019; 90:102-113. [PMID: 30290006 DOI: 10.1111/cen.13874] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 10/01/2018] [Accepted: 10/01/2018] [Indexed: 12/28/2022]
Abstract
OBJECTIVE Metabolically healthy individuals are known to be resistant to cardiovascular disease development. However, a considerable fraction of those individuals shows deteriorated metabolic health over time. Although skeletal muscle is the primary insulin-responsive target organ, a longitudinal investigation of the skeletal muscle mass in relation to the development of metabolically unhealthy phenotype has not been performed. We aimed to evaluate whether greater skeletal muscle mass is an independent protective factor for the development of metabolically unhealthy phenotype. DESIGN, PARTICIPANTS AND MEASUREMENTS We conducted a retrospective cohort study with 9033 metabolically healthy volunteers who underwent routine health examinations in 2012 and a follow-up examination in 2016. Obesity was defined as Asian-Pacific body mass index criterion ≥25 kg/m2 . Subjects with fewer than two risk factors (elevated blood pressure, triglyceride, glucose, high-sensitivity C-reactive protein, insulin resistance and decreased high-density lipoprotein cholesterol levels) were characterized as metabolically healthy using Wildman criteria. RESULTS At the 4-year follow-up, approximately one-fourth of the nonobese participants and half of the participants with obesity showed metabolic deterioration. In nonobese men and women, higher appendicular skeletal muscle mass (ASM)/weight at baseline was significantly associated with decreased risk of metabolic deterioration. Compared to the lowest quartile of ASM/weight, the adjusted odds ratios (95% confidence intervals) of the highest quartile were 0.68 (0.52-0.89) in nonobese men and 0.64 (0.46-0.90) in nonobese women. However, this association was not observed in obese subjects. CONCLUSIONS Greater skeletal muscle mass at baseline is significantly associated with maintenance of metabolically healthy status, especially in nonobese individuals.
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Affiliation(s)
- Min Jung Lee
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun-Hee Kim
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Jin Bae
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jaewon Choe
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chang Hee Jung
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Woo Je Lee
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hong-Kyu Kim
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Fingeret M, Marques-Vidal P, Vollenweider P. Incidence of type 2 diabetes, hypertension, and dyslipidemia in metabolically healthy obese and non-obese. Nutr Metab Cardiovasc Dis 2018; 28:1036-1044. [PMID: 30139688 DOI: 10.1016/j.numecd.2018.06.011] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Revised: 06/08/2018] [Accepted: 06/13/2018] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND AIMS Metabolically healthy obese (MHO) individuals are devoid of many metabolic abnormalities, but how this condition is maintained over time remains debated. We assessed the prevalence of MHO over time and the incidence of hypertension (HTN), dyslipidemia, and type 2 diabetes mellitus (T2DM) in MHO as compared with metabolically healthy non obese (MHNO). METHODS AND RESULTS Prospective, population-based study including 3038 participants (49.9 ± 9.9 years; 1753 women) free from metabolic syndrome and cardiovascular disease at baseline and examined after a follow-up of 5.6 years and 10.9 years on average. At each follow-up, prevalence of MHO, MHNO, metabolically unhealthy not obese (MUNO), and metabolically unhealthy obese (MUO), as well as of HTN, dyslipidemia, and T2DM, was calculated and stratified by sex, age group, and education. At baseline, 179 (5.7%) MHO participants were identified, of which 62 (34.6%) and 79 (44.1%) remained MHO at 5.6 and 10.9 years follow-up, respectively. At 5.6 years follow-up, MHO participants were more likely to develop low HDL or be on hypolipidemic medication [multivariable-adjusted OR (95% CI): 1.56 (1.02-2.38)], to have dyslipidemia [1.94 (1.33-2.82)], and high triglycerides [2.07 (1.36-3.14)] than MHNO. At 10.9 years follow-up, MHO participants were significantly more likely to develop T2DM [3.44 (1.84-6.43)], dyslipidemia [1.64 (1.14-2.38)], and low HDL or be prescribed hypolipidemic medication [1.57 (1.08-2.27)] than MHNO. Conversely, no differences were found regarding hypertension. CONCLUSION A considerable fraction of MHO individuals lose their status over time, and in metabolically healthy adults, obesity confers a higher risk of developing cardiovascular risk factors.
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Affiliation(s)
- M Fingeret
- NYU School of Medicine, New York, NY, USA.
| | - P Marques-Vidal
- Department of Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
| | - P Vollenweider
- Department of Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
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Eckel N, Li Y, Kuxhaus O, Stefan N, Hu FB, Schulze MB. Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease risk across BMI categories in 90 257 women (the Nurses' Health Study): 30 year follow-up from a prospective cohort study. Lancet Diabetes Endocrinol 2018; 6:714-724. [PMID: 29859908 DOI: 10.1016/s2213-8587(18)30137-2] [Citation(s) in RCA: 262] [Impact Index Per Article: 37.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 04/16/2018] [Accepted: 04/16/2018] [Indexed: 12/28/2022]
Abstract
BACKGROUND Cardiovascular disease risk among individuals across different categories of BMI might depend on their metabolic health. It remains unclear to what extent metabolic health status changes over time and whether this affects cardiovascular disease risk. In this study, we aimed to examine the association between metabolic health and its change over time and cardiovascular disease risk across BMI categories. METHODS Between June and December, 1976, 121 701 female nurses were recruited to the Nurses' Health Study (NHS) of whom 103 298 returned a questionnaire in 1980 used as baseline in this study. After excluding women with a history of cardiovascular disease or cancer, with missing body weight and with underweight. 90 257 women were followed-up from 1980 to 2010 for incident cardiovascular disease. Participants were cross-classified by BMI categories, metabolic health (defined by absence of diabetes, hypertension and hypercholesterolaemia), and change in metabolic health status during follow-up. The cardiovascular component of the NHS is registered with ClinicalTrials.gov, number NCT00005152. FINDINGS During 2 127 391 person-years of follow-up with a median follow-up of 24 years, we documented 6306 cases of cardiovascular disease including 3304 myocardial infarction cases and 3080 strokes. Cardiovascular disease risk of women with metabolically healthy obesity was increased compared with women with metabolically healthy normal weight (HR 1·39, 95% CI 1·15-1·68), but risk was considerably higher in women with metabolically unhealthy normal weight (2·43, 2·19-2·68), overweight (2·61, 2·36-2·89) and obesity (3·15, 2·83-3·50). The majority of metabolically healthy women converted to unhealthy phenotypes (2555 [84%] of 3027 women with obesity, 22 215 [68%] of 32 882 women with normal-weight after 20 years). Women who maintained metabolically healthy obesity during follow-up were still at a higher cardiovascular disease risk compared with women with stable healthy normal weight (HR 1·57, 1·03-2·38), yet this risk was lower than for initially metabolically healthy women who converted to an unhealthy phenotype (normal-weight 1·90, 1·66-2·17 vs obesity 2·74, 2·30-3·27). Particularly incident diabetes and hypertension increased the risk among women with initial metabolic health. INTERPRETATION Even when metabolic health is maintained during long periods of time, obesity remains a risk factor for cardiovascular disease. However, risks are highest for metabolically unhealthy women across all BMI categories. A large proportion of metabolically healthy women converted to an unhealthy phenotype over time across all BMI categories, which is associated with an increased cardiovascular disease risk. FUNDING US National Institutes of Health, German Federal Ministry of Education and Research.
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Affiliation(s)
- Nathalie Eckel
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; University of Potsdam, Institute of Nutritional Sciences, Nuthetal, Germany
| | - Yanping Li
- Department of Nutrition, Harvard T H Chan School of Public Health, Boston, MA, USA
| | - Olga Kuxhaus
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Norbert Stefan
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center München at the University of Tübingen, Tübingen, Germany; Department of Internal Medicine IV, University Hospital of Tübingen, Tübingen, Germany
| | - Frank B Hu
- Department of Nutrition, Harvard T H Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Matthias B Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; University of Potsdam, Institute of Nutritional Sciences, Nuthetal, Germany.
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Abenavoli L, Di Renzo L, Boccuto L, Alwardat N, Gratteri S, De Lorenzo A. Health benefits of Mediterranean diet in nonalcoholic fatty liver disease. Expert Rev Gastroenterol Hepatol 2018; 12:873-881. [PMID: 30033779 DOI: 10.1080/17474124.2018.1503947] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Insulin resistance and obesity-related inflammatory status, associated with genetic, dietary, and lifestyle factors, are involved in its pathogenesis. There is no consensus concerning the pharmacological treatment of NAFLD. However, the international guidelines agree to define a dietetic nutritional management to achieve weight loss, as an essential component of any therapeutic strategy. Areas covered: An overview on the beneficial effects of the Mediterranean diet in the prevention and treatment of NAFLD. Expert commentary: On the basis of its components, the literature reports the beneficial effects of the Mediterranean diet in preventing major chronic diseases, including obesity, diabetes, cardiovascular diseases, and some forms of cancers. In recent years, a growing body of evidence has supported the idea that the Mediterranean diet, associated with physical activity and cognitive behavior therapy, may be the reference nutritional profile for the prevention and the treatment of NAFLD patients.
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Affiliation(s)
- Ludovico Abenavoli
- a Department of Health Sciences , University Magna Graecia , Catanzaro , Italy
| | - Laura Di Renzo
- b Section of Clinical Nutrition and Nutrigenomic, Department of Biomedicine and Prevention , University of Rome Tor Vergata , Rome , Italy
| | - Luigi Boccuto
- c Greenwood Genetic Center, Greenwood , Clemson University School of Health Research , Clemson , SC , USA
| | - Nuha Alwardat
- b Section of Clinical Nutrition and Nutrigenomic, Department of Biomedicine and Prevention , University of Rome Tor Vergata , Rome , Italy
| | - Santo Gratteri
- d Department of Surgery and Medical Science , University Magna Graecia , Catanzaro , Italy
| | - Antonino De Lorenzo
- b Section of Clinical Nutrition and Nutrigenomic, Department of Biomedicine and Prevention , University of Rome Tor Vergata , Rome , Italy
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Xie J, Zhang S, Yu X, Yang Y, Liu Z, Yuan G, Hu S. Association between Liver Enzymes with Metabolically Unhealthy Obese Phenotype. Lipids Health Dis 2018; 17:198. [PMID: 30134916 PMCID: PMC6106819 DOI: 10.1186/s12944-018-0847-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Accepted: 08/10/2018] [Indexed: 01/07/2023] Open
Abstract
Background Obesity could be classified into two phenotypes: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). This study investigated the ability of liver enzymes to identify obesity phenotype. Methods We conducted a cross-sectional study in 2197 obese adults (age > 40 years and BMI ≥25 kg/m2) in a rural area of central China. Results In this population, 75% of the participants have more than one cardiometabolic risk factor. Both GGT and ALT were strongly related to the MUHO phenotype. The association between the fourth quartile of GGT and MUHO risk was strong and independent of confounder risk factors in both genders (adjusted ORs, 1.73 (95%CI 1.03–2.92) for male and 1.82 (95%CI 1.29–2.57) for female). The association between the fourth quartile of ALT and MUHO risk was strong and independent in female, but not in male (adjusted ORs, 1.65 (95%CI 0.86–3.19) for male and 1.88 (95%CI 1.29–2.75) for female). Additionally, AST was not associated with MUHO phenotype. Conclusions Both GGT and ALT are effective markers for identifying MUHO in this population. Furthermore, the ability of GGT may be superior to ALT in male.
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Affiliation(s)
- Junhui Xie
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei Province, China
| | - Shujun Zhang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei Province, China
| | - Xuefeng Yu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei Province, China.
| | - Yan Yang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei Province, China
| | - Zhelong Liu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei Province, China
| | - Gang Yuan
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei Province, China
| | - Shuhong Hu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, Hubei Province, China
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Rodriguez-Garcia E, Ruiz-Nava J, Santamaria-Fernandez S, Fernandez-Garcia JC, Vargas-Candela A, Yahyaoui R, Tinahones FJ, Bernal-Lopez MR, Gomez-Huelgas R. Implications of the Mediterranean diet and physical exercise on the lipid profile of metabolically healthy obese women as measured by nuclear magnetic resonance spectroscopy ( 1 H NMR). Chem Phys Lipids 2018; 213:68-75. [DOI: 10.1016/j.chemphyslip.2018.03.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Revised: 03/08/2018] [Accepted: 03/22/2018] [Indexed: 01/28/2023]
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Fate of the metabolically healthy obese-is this term a misnomer? A study from the Clinical Practice Research Datalink. Int J Obes (Lond) 2018; 43:1093-1101. [PMID: 29777229 DOI: 10.1038/s41366-018-0096-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Revised: 03/06/2018] [Accepted: 04/02/2018] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The metabolically healthy obese (MHO) phenotype may express typical characteristics on long-term follow-up. Little is known about the initiation of this phenotypes and its future stability. AIM The Clinical Practice Research Datalink (CPRD) is a large-scale primary care database. The aim of this study was to assess the stability of, and evaluate the factors associated with a transition into an unhealthy outcome in, a MHO population in the UK. METHODS The CPRD was interrogated for a diagnosis of 'obesity' and cross-referenced with a body mass index (BMI) ≥35 kg/m2; participants were further classified as MH using a clinical diagnostic code or a relative therapeutic code. A hazard cox regression univariate and multivariate analysis evaluated the time to transition for independent variables. RESULTS There were 231,399 patients with a recorded BMI of 35 kg/m2 or greater. Incomplete records were eliminated and follow-up limited to 300 months, the cohort was reduced to 180,560 patients. The prevalence of MHO within the obese population from the CPRD was 128,191/180,560 (71%). MHO individuals, who were of male gender (hazard ratio (HR) 1.23 (1.21-1.25), p = < 0.01), older age group (HR 3.93 (3.82-4.04), p = < 0.01), BMI of 50-60 kg/m2 at baseline (HR 1.32(1.26-1.38), p = 0.01), smokers (HR 1.07(1.05-1.09), p = < 0.01) and regionally from North West England (HR 1.15(1.09-1.21), p = < 0.01) were more prone to an unhealthy transition (to develop comorbidities). Overall, of those MH at baseline, 71,485/128,191(55.8%) remained healthy on follow-up, with a mean follow-up of 113.5 (standard deviations (SD) 78.6) months or 9.4 (SD 6.6) years. CONCLUSIONS From this unique large data set, there is a greater prevalence of MHO individuals in the UK population than in published literature elsewhere. Female gender, younger age group, and lower initial weight and BMI were found to be significant predictors of sustained metabolic health in this cohort. However, there remains a steady progressive transition from a healthy baseline over the years.
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Slagter SN, Corpeleijn E, van der Klauw MM, Sijtsma A, Swart-Busscher LG, Perenboom CWM, de Vries JHM, Feskens EJM, Wolffenbuttel BHR, Kromhout D, van Vliet-Ostaptchouk JV. Dietary patterns and physical activity in the metabolically (un)healthy obese: the Dutch Lifelines cohort study. Nutr J 2018; 17:18. [PMID: 29433580 PMCID: PMC5809859 DOI: 10.1186/s12937-018-0319-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 01/04/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Diversity in the reported prevalence of metabolically healthy obesity (MHO), suggests that modifiable factors may be at play. We evaluated differences in dietary patterns and physical activity between MHO and metabolically unhealthy obesity (MUO). METHODS Cross-sectional data of 9270 obese individuals (30-69 years) of the Lifelines Cohort Study was used. MHO was defined as obesity and no metabolic syndrome risk factors and no cardiovascular disease history. MUO was defined as obesity and ≥2 metabolic syndrome risk factors. Sex-specific associations of dietary patterns (identified by principal component analysis) and physical activity with MHO were assessed by multivariable logistic regression (reference group: MUO). Analyses were adjusted for multiple covariates. RESULTS Among 3442 men and 5828 women, 10.2% and 24.4% had MHO and 56.9% and 35.3% MUO, respectively. We generated four obesity-specific dietary patterns. Two were related to MHO, and in women only. In the highest quartile (Q) of 'bread, potatoes and sweet snacks' pattern, odds ratio (OR) (95% CI) for MHO was 0.52 (0.39-0.70). For the healthier pattern 'fruit, vegetables and fish', an OR of 1.36 (1.09-1.71) in Q3 and 1.55 (1.21-1.97) in Q4 was found for MHO. For physical activity, there was a positive association between moderate physical activity and vigorous physical activity in the highest tertile and MHO in women and men, respectively (OR 1.19 (1.01-1.41) and OR 2.02 (1.50-2.71)). CONCLUSION The healthier diet -characterized by 'fruit, vegetables and fish'- and moderate physical activity in women, and vigorous physical activity in men may be related to MHO. The (refined) carbohydrate-rich 'bread, potatoes and sweet snacks' dietary pattern was found to counteract MHO in women.
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Affiliation(s)
- Sandra N. Slagter
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, HPC AA31, P.O. Box 30001, 9700 RB Groningen, The Netherlands
| | - Eva Corpeleijn
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands
| | - Melanie M. van der Klauw
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, HPC AA31, P.O. Box 30001, 9700 RB Groningen, The Netherlands
| | - Anna Sijtsma
- Lifelines Cohort Study, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands
| | - Linda G. Swart-Busscher
- Department of Paramedical Sciences, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands
| | - Corine W. M. Perenboom
- Division of Human Nutrition, Wageningen University, PO Box 17, 6700 AA Wageningen, The Netherlands
| | - Jeanne H. M. de Vries
- Division of Human Nutrition, Wageningen University, PO Box 17, 6700 AA Wageningen, The Netherlands
| | - Edith J. M. Feskens
- Division of Human Nutrition, Wageningen University, PO Box 17, 6700 AA Wageningen, The Netherlands
| | - Bruce H. R. Wolffenbuttel
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, HPC AA31, P.O. Box 30001, 9700 RB Groningen, The Netherlands
| | - Daan Kromhout
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands
| | - Jana V. van Vliet-Ostaptchouk
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, HPC AA31, P.O. Box 30001, 9700 RB Groningen, The Netherlands
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Abstract
Obesity is a complex disease with many causal factors, associated with multiple comorbidities that contribute to significant morbidity and mortality. It is a highly prevalent disease that poses an enormous health and economic burden to society. This article reviews the mechanisms of obesity and its related comorbidities.
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Affiliation(s)
- Jagriti Upadhyay
- Section of Endocrinology, Diabetes and Metabolism, Boston VA Healthcare System, 150 South Huntington Avenue, Boston, MA 02130, USA; Division of Endocrinology, Boston Medical Center, Boston University, 88 East Newton Street, Boston, MA 02118; Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
| | - Olivia Farr
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
| | - Nikolaos Perakakis
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
| | - Wael Ghaly
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
| | - Christos Mantzoros
- Section of Endocrinology, Diabetes and Metabolism, Boston VA Healthcare System, 150 South Huntington Avenue, Boston, MA 02130, USA; Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
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Dietze EC, Chavez TA, Seewaldt VL. Obesity and Triple-Negative Breast Cancer: Disparities, Controversies, and Biology. THE AMERICAN JOURNAL OF PATHOLOGY 2017. [PMID: 29128565 DOI: 10.1016/j.ajpath.2017.09.018"] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Once considered a problem of Western nations, obesity (body mass index ≥30 kg/m2) has rapidly increased since the 1970s to become a major threat to world health. Since 1970, the face of obesity has changed from a disease of affluence and abundance to a disease of poverty. During the last 10 years, studies have mechanistically linked obesity and an obese tumor microenvironment with signaling pathways that predict aggressive breast cancer biology. For example, in the United States, African American women are more likely than non-Hispanic European American women to be obese and to be diagnosed with triple-negative breast cancer (TNBC). In 2008, the Carolina Breast Study found that obesity (increased waist/hip ratio) was linked to an increased incidence of TNBC in premenopausal and postmenopausal African American women. Subsequently, several groups have investigated the potential link between obesity and TNBC in African American women. To date, the data are complex and sometimes contradictory. We review epidemiologic studies that investigated the potential association among obesity, metabolic syndrome, and TNBC in African American women and mechanistic studies that link insulin signaling to the obese breast microenvironment, tissue inflammation, and aggressive TNBC biology.
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Affiliation(s)
- Eric C Dietze
- Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Tanya A Chavez
- Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Victoria L Seewaldt
- Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, California.
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Dietze EC, Chavez TA, Seewaldt VL. Obesity and Triple-Negative Breast Cancer: Disparities, Controversies, and Biology. THE AMERICAN JOURNAL OF PATHOLOGY 2017; 188:280-290. [PMID: 29128565 DOI: 10.1016/j.ajpath.2017.09.018] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Revised: 08/07/2017] [Accepted: 09/26/2017] [Indexed: 12/13/2022]
Abstract
Once considered a problem of Western nations, obesity (body mass index ≥30 kg/m2) has rapidly increased since the 1970s to become a major threat to world health. Since 1970, the face of obesity has changed from a disease of affluence and abundance to a disease of poverty. During the last 10 years, studies have mechanistically linked obesity and an obese tumor microenvironment with signaling pathways that predict aggressive breast cancer biology. For example, in the United States, African American women are more likely than non-Hispanic European American women to be obese and to be diagnosed with triple-negative breast cancer (TNBC). In 2008, the Carolina Breast Study found that obesity (increased waist/hip ratio) was linked to an increased incidence of TNBC in premenopausal and postmenopausal African American women. Subsequently, several groups have investigated the potential link between obesity and TNBC in African American women. To date, the data are complex and sometimes contradictory. We review epidemiologic studies that investigated the potential association among obesity, metabolic syndrome, and TNBC in African American women and mechanistic studies that link insulin signaling to the obese breast microenvironment, tissue inflammation, and aggressive TNBC biology.
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Affiliation(s)
- Eric C Dietze
- Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Tanya A Chavez
- Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Victoria L Seewaldt
- Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, California.
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Lin H, Zhang L, Zheng R, Zheng Y. The prevalence, metabolic risk and effects of lifestyle intervention for metabolically healthy obesity: a systematic review and meta-analysis: A PRISMA-compliant article. Medicine (Baltimore) 2017; 96:e8838. [PMID: 29381992 PMCID: PMC5708991 DOI: 10.1097/md.0000000000008838] [Citation(s) in RCA: 95] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND We conducted a systematic review and meta-analysis to firstly obtain a reliable estimation of the prevalence of metabolically healthy obese (MHO) individuals in obesity, then assessed the risk of developing metabolic abnormalities (MA) among MHO individuals. At last, we evaluated the effects of traditional lifestyle interventions on metabolic level for MHO subjects. METHODS A systematic review and meta-analysis (PRISMA) guideline were conducted, and original studies were searched up to December 31, 2016. The prevalence of MHO in obesity from each study was pooled using random effects models. The relative risks (RRs) were pooled to determine the risk of developing MA for MHO compared with metabolically healthy normal-weight (MHNW) subjects. For the meta-analysis of intervention studies, the mean difference and standardized mean differences were both estimated for each metabolic parameter within each study, and then pooled using a random-effects model. RESULTS Overall, 40 population-based studies reported the prevalence of MHO in obesity, 12 cohort studies and 7 intervention studies were included in the meta-analysis. About 35.0% obese individuals were metabolically healthy in the obese subjects. There were dramatic differences in the prevalence among different areas. However, 0.49 (95% confidence intervals [CI]: 0.38 to 0.60) of the MHO individuals would develop one or more MA within 10 years. Compared with MHNW subjects, the MHO subjects presented higher risk of incident MA (pooled RR = 1.80, 95%CI: 1.53-2.11). Following intervention, there was certain and significant improvement of metabolic state for metabolically abnormal obesity (MAO) subjects. Only diastolic blood pressure had reduced for MHO individuals after intervention. CONCLUSIONS Almost one-third of the obese individuals are in metabolic health. However, they are still at higher risk of advancing to unhealthy state. Therefore, it is still needed to advise MHO individuals to maintain or adopt a healthy lifestyle, so as to counterbalance the adverse effects of obesity.
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Affiliation(s)
| | - Liqun Zhang
- Department of Intensive Care Unit, Zhejiang Putuo Hospital, Zhoushan
| | - Ruizhi Zheng
- Department of Epidemiology and Statistic, Zhejiang University, Hangzhou, Zhejiang
| | - Yishan Zheng
- Department of Intensive Care Unit, The Second Hospital of Nanjing. Teaching Hospital of Medical School of Nanjing University, Nanjing, Jiangsu, China
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Incidence of components of metabolic syndrome in the metabolically healthy obese over 9 years follow-up: the Atherosclerosis Risk In Communities study. Int J Obes (Lond) 2017; 42:295-301. [PMID: 28990591 PMCID: PMC5876059 DOI: 10.1038/ijo.2017.249] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2017] [Revised: 09/13/2017] [Accepted: 09/15/2017] [Indexed: 01/01/2023]
Abstract
Background Some obese adults are not afflicted by the metabolic abnormalities often associated with obesity [the “metabolically healthy obese” (MHO)], however, they may be at increased risk of developing cardiometabolic abnormalities in the future. Little is known about the relative incidence of individual components of metabolic syndrome (MetSyn). Methods We used data from a multi-center, community-based cohort aged 45–64 years at recruitment [the Atherosclerosis Risk in Communities (ARIC) study] to examine the first appearance of any MetSyn component, excluding waist circumference. Body mass index (BMI, kg/m2) and cardiometabolic data were collected at four triennial visits. Our analysis included 3,969 adults who were not underweight and free of the components of MetSyn at the initial visit. Participants were classified as metabolically healthy normal weight (MHNW), over weight (MHOW) and MHO at each visit. Adjusted hazard ratios (HR) and 95% confidence intervals were estimated with proportional hazards regression models. Results The relative rate of developing each risk factor was higher among MHO than MHNW with the strongest association noted for elevated fasting glucose [MHO vs. MHNW, HR: 2.33 (1.77, 3.06)]. MHO was also positively associated with elevated triglycerides [HR: 1.63 (1.27, 2.09)], low HDL-C [HR: 1.68 (1.32, 2.13)] and elevated blood pressure [HR: 1.54 (1.26, 1.88)]. A similar, but less pronounced pattern was noted among the MHOW vs. MHNW. Conclusions We conclude that even among apparently healthy individuals, obesity and overweight are related to more rapid development of at least 1 cardiometabolic risk factor, and that elevations in blood glucose develop most rapidly.
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Eftekharzadeh A, Asghari G, Serahati S, Hosseinpanah F, Azizi A, Barzin M, Mirmiran P, Azizi F. Predictors of incident obesity phenotype in nonobese healthy adults. Eur J Clin Invest 2017; 47:357-365. [PMID: 28294315 DOI: 10.1111/eci.12743] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2016] [Accepted: 03/06/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Despite their different cardiovascular consequences, little is known about predictors of metabolically healthy (MHO) and metabolically unhealthy obesity (MUHO). This cohort study was designed to address this question in participants of the Tehran Lipid and Glucose Study. MATERIALS AND METHODS Employing the Joint Interim Statement (JIS) metabolic syndrome criteria to define MHO/MUHO phenotypes, nonobese, otherwise healthy individuals, aged > 20 years (n = 3489) were recruited and followed up for a median of 13·4 years. RESULTS At the follow-up, MHO incidence rate in obese individuals was 36·6%. Comparing MHO vs. MUHO, female gender [odds ratio (OR) = 3·28, 95% confidence interval (CI) 1·27, 8·46)], increased body mass index (BMI; OR = 1·32, 95% CI: 1·12, 1·60) and elevated high-density lipoprotein cholesterol (HDL-C) levels (OR = 1·04, 95% CI: 1·02, 1·07) were related to higher odds of incident MHO, while older age (OR = 0·95, 95% CI: 0·92, 0·98), increased waist circumference (WC; OR = 0·86, 95% CI: 0·81, 0·91), higher WC gain (OR = 0·91, 95% CI: 0·87, 0·95) and increased diastolic blood pressure (DBP; OR = 0·94, 95% CI: 0·91, 0·98) prevented progression towards MHO. CONCLUSIONS While baseline BMI and WC were detrimental for developing MHO vs. MUHO, gender was the strongest predictor of incident obesity phenotype in healthy nonobese individuals.
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Affiliation(s)
- Anita Eftekharzadeh
- Obesity Research Center, Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Golaleh Asghari
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Serahati
- Obesity Research Center, Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farhad Hosseinpanah
- Obesity Research Center, Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Azizi
- Endocrine Research Center, Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Barzin
- Obesity Research Center, Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parvin Mirmiran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Phillips CM. Metabolically healthy obesity across the life course: epidemiology, determinants, and implications. Ann N Y Acad Sci 2016; 1391:85-100. [PMID: 27723940 DOI: 10.1111/nyas.13230] [Citation(s) in RCA: 125] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Revised: 08/09/2016] [Accepted: 08/18/2016] [Indexed: 12/24/2022]
Abstract
In recent years, different subphenotypes of obesity have been described, including metabolically healthy obesity (MHO), in which a proportion of obese individuals, despite excess body fat, remain free of metabolic abnormalities and increased cardiometabolic risk. In the absence of a universally accepted set of criteria to classify MHO, the reported prevalence estimates vary widely. Our understanding of the determinants and stability of MHO over time and the associated cardiometabolic and mortality risks is improving, but many questions remain. For example, whether MHO is truly benign is debatable, and whether risk stratification of obese individuals on the basis of their metabolic health status may offer new opportunities for more personalized approaches in diagnosis, intervention, and treatment of diabetes remains speculative. Furthermore, as most of the research to date has focused on MHO in adults, little is known about childhood MHO. In this review, we focus on the epidemiology, determinants, stability, and health implications of MHO across the life course.
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Affiliation(s)
- Catherine M Phillips
- HRB Centre for Diet and Health Research, Department of Epidemiology and Public Health, University College Cork, Cork, Ireland; and HRB Centre for Diet and Health Research, School of Public Health, Physiotherapy and Sports Science, University College Dublin, Dublin, Ireland
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Abstract
Obesity is a top public health priority but interventions to reverse the condition have had limited success. About one-in-three obese adults are free of metabolic risk factor clustering and are considered 'healthy', and much attention has focused on the implications of this state for obesity management. Areas covered: We searched for individual studies, systematic reviews, and meta-analyses which examined correlates and outcomes of metabolically healthy obesity. We discuss the key roles of fat distribution and physical activity in determining healthy vs. unhealthy obesity and report a greatly increased risk of incident type 2 diabetes associated with healthy obesity vs. healthy normal weight, among other outcomes. We argue that despite inconsistencies in the definition, patterns across studies clearly show that healthy obesity is a state of intermediate disease risk. Expert commentary: Given the current state of population-level evidence, we conclude that obesity and metabolic dysfunction are inseparable and that healthy obesity is best viewed only as a state of relative health but not of absolute health. We recommend that weight loss through energy restriction be a stand-alone target in addition to increased physical activity for minimising risk of future disease.
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Affiliation(s)
- J A Bell
- a Department of Epidemiology & Public Health , University College London , London , UK
- b School of Sport, Exercise & Health Sciences, Loughborough University , Loughborough , UK
| | - M Hamer
- b School of Sport, Exercise & Health Sciences, Loughborough University , Loughborough , UK
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Doumatey AP, Zhou J, Zhou M, Prieto D, Rotimi CN, Adeyemo A. Proinflammatory and lipid biomarkers mediate metabolically healthy obesity: A proteomics study. Obesity (Silver Spring) 2016; 24:1257-65. [PMID: 27106679 PMCID: PMC4882259 DOI: 10.1002/oby.21482] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Revised: 01/11/2016] [Accepted: 01/11/2016] [Indexed: 12/25/2022]
Abstract
OBJECTIVE The metabolically healthy obesity (MHO) phenotype is an important obesity subtype in which obesity is not accompanied by any metabolic comorbidity. However, the underlying molecular mechanisms remain elusive. In this study, a shotgun proteomics approach to identify circulating biomolecules and pathways associated with MHO was used. METHODS The subjects were 20 African-American women: 10 MHO cases and 10 metabolically abnormal individuals with obesity (MAO) controls. Serum proteins were detected and quantified using label-free proteomics. Differential expression of proteins between the two groups was analyzed, and the list of differentially expressed proteins was analyzed to determine enriched biological pathways. RESULTS Twenty proteins were differentially expressed between MHO and controls. These proteins included: hemoglobin subunits (HBA1, P = 6.00 × 10(-18) ), haptoglobin-related protein (HPR, P = 1.2 × 10(-15) ), apolipoproteins (APOB-100, P = 1.50 × 10(-40) ; APOA4, P = 1.1 × 10(-14) ), retinol-binding protein 4 (RBP4, P = 7.1 × 10(-08) ), and CRP (P = 2.0 × 10(-04) ). MHO was associated with lower levels of proinflammatory and higher levels of anti-inflammatory biomarkers when compared with MAO. Pathway analysis showed enrichment of lipids and inflammatory pathways, including LXR/RXR and FXR/RXR activation, and acute phase response signaling. CONCLUSIONS These findings suggested that protection from dysregulated inflammatory and lipid processes were primary molecular hallmarks of MHO. The candidate biomarkers (AHSG, RBP4, and APOA4) identified in this study are potential prognostic markers for MHO.
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Affiliation(s)
- Ayo Priscille Doumatey
- Center for Research on Genomics and Global HealthNational Human Genome Research Institute, National Institutes of HealthBethesdaMarylandUSA
| | - Jie Zhou
- Center for Research on Genomics and Global HealthNational Human Genome Research Institute, National Institutes of HealthBethesdaMarylandUSA
| | - Ming Zhou
- Laboratory of Proteomics and Analytical Technologies (LPAT) Leidos Biomedical Research IncNational Cancer Institute, National Institutes of HealthFrederickMarylandUSA
| | - DaRue Prieto
- Laboratory of Proteomics and Analytical Technologies (LPAT) Leidos Biomedical Research IncNational Cancer Institute, National Institutes of HealthFrederickMarylandUSA
| | - Charles N. Rotimi
- Center for Research on Genomics and Global HealthNational Human Genome Research Institute, National Institutes of HealthBethesdaMarylandUSA
| | - Adebowale Adeyemo
- Center for Research on Genomics and Global HealthNational Human Genome Research Institute, National Institutes of HealthBethesdaMarylandUSA
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Phillips CM. Metabolically Healthy Obesity: Personalised and Public Health Implications. Trends Endocrinol Metab 2016; 27:189-191. [PMID: 26915289 DOI: 10.1016/j.tem.2016.02.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2015] [Revised: 01/26/2016] [Accepted: 02/05/2016] [Indexed: 12/27/2022]
Abstract
Obesity is a heterogeneous condition; thus, metabolic abnormalities and cardiometabolic risk vary among obese individuals, with a significant proportion considered to be metabolically healthy. However, whether these individuals are truly healthy remains controversial and, therefore, a better understanding of such phenotypes may offer opportunities to improve current obesity diagnosis, intervention, and treatment.
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Affiliation(s)
- Catherine M Phillips
- HRB Centre for Diet and Health Research, Department of Epidemiology and Public Health, University College Cork, Cork, Ireland; HRB Centre for Diet and Health Research, School of Public Health, Physiotherapy and Sports Science, University College Dublin, Dublin, Ireland.
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