ORIGINAL ARTICLE Open questions about metabolically normal obesity

Subsets of obese subjects without any cardiometabolic risk factors have been repeatedly described. This raises questions whether obesity ‘per se’ enhances the risk for cardiovascular or metabolic diseases and whether healthy obese subjects would benefit from a medical treatment. In order to answer these questions, as a first step, an expert consensus should be reached for the definition of metabolic normality. In fact, up to now, different parameters related to the metabolic syndrome and/or to insulin sensitivity have been utilized across studies. Once an agreement is reached, population-based studies should be undertaken to establish the incidence of metabolic normality among obese subjects. Furthermore, many other parameters such as age, sex, race, fat distribution and physical activity should be monitored to obtain results representative of a general population. Longitudinal studies aimed at investigating the evolution of the cardiometabolic profile of healthy obese subjects are also needed. In conclusion, data from the literature strongly suggest that a regular surveillance of the cardiometabolic parameters and a prevention of any further weight gain should be applied to healthy obese individuals, whereas possible benefits of a weight loss treatment are still a matter of debate. International Journal of Obesity (2010) 34, S18–S23; doi:10.1038/ijo.2010.235

[1]  V. Messier,et al.  Identifying Metabolically Healthy but Obese Individuals in Sedentary Postmenopausal Women , 2010, Obesity.

[2]  L. Lynch,et al.  The Relationship of Omental and Subcutaneous Adipocyte Size to Metabolic Disease in Severe Obesity , 2010, PloS one.

[3]  L. McLaren,et al.  Social class, gender, and time use: implications for the social determinants of body weight? , 2009, Health reports.

[4]  S. Nikkari,et al.  Lipids in Health and Disease , 2009 .

[5]  J. Kuk,et al.  Are Metabolically Normal but Obese Individuals at Lower Risk for All-Cause Mortality? , 2009, Diabetes Care.

[6]  E. Demerath,et al.  Genetic analysis of self-reported physical activity and adiposity: The Southwest Ohio Family Study , 2009, Public Health Nutrition.

[7]  A. Tchernof,et al.  Fat Depot‐specific Impact of Visceral Obesity on Adipocyte Adiponectin Release in Women , 2009, Obesity.

[8]  M. Roden,et al.  Ectopic lipids and organ function , 2009, Current opinion in lipidology.

[9]  C. Aguilar-Salinas,et al.  High adiponectin concentrations are associated with the metabolically healthy obese phenotype. , 2008, The Journal of clinical endocrinology and metabolism.

[10]  W. Hul,et al.  Association of SIRT1 gene variation with visceral obesity , 2008, Human Genetics.

[11]  K. Reynolds,et al.  The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999-2004). , 2008, Archives of internal medicine.

[12]  Fritz Schick,et al.  Identification and characterization of metabolically benign obesity in humans. , 2008, Archives of internal medicine.

[13]  G. Siest,et al.  Five-year alterations in BMI are associated with clustering of changes in cardiovascular risk factors in a gender-dependant way: the Stanislas study , 2008, International Journal of Obesity.

[14]  E. Lambert,et al.  Determinants of Insulin‐resistant Phenotypes in Normal‐weight and Obese Black African Women , 2008, Obesity.

[15]  R. Rabasa-Lhoret,et al.  Metabolically healthy but obese women: effect of an energy-restricted diet , 2008, Diabetologia.

[16]  Kieran Clarke,et al.  Uncomplicated obesity is associated with abnormal aortic function assessed by cardiovascular magnetic resonance , 2008, Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance.

[17]  R. Vasan,et al.  Bmc Medical Genetics Genome-wide Association to Body Mass Index and Waist Circumference: the Framingham Heart Study 100k Project , 2022 .

[18]  Sabine Brasche,et al.  Weight change, weight cycling and mortality in the ERFORT Male Cohort Study , 2007, European Journal of Epidemiology.

[19]  Tracey McLaughlin,et al.  Heterogeneity in the prevalence of risk factors for cardiovascular disease and type 2 diabetes mellitus in obese individuals: effect of differences in insulin sensitivity. , 2007, Archives of internal medicine.

[20]  J. Meigs,et al.  Insulin Resistance as Estimated by Homeostasis Model Assessment Predicts Incident Symptomatic Cardiovascular Disease in Caucasian Subjects From the General Population , 2007, Diabetes Care.

[21]  C. Tsigos,et al.  Stress, Visceral Obesity, and Metabolic Complications , 2006, Annals of the New York Academy of Sciences.

[22]  Ralph B D'Agostino,et al.  Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. , 2006, The Journal of clinical endocrinology and metabolism.

[23]  Y. Jang,et al.  Weight loss effect on inflammation and LDL oxidation in metabolically healthy but obese (MHO) individuals: low inflammation and LDL oxidation in MHO women , 2006, International Journal of Obesity.

[24]  D. Prud'homme,et al.  Psychosocial profile of the metabolically healthy but obese postmenopausal woman. , 2006, Diabetes & metabolism.

[25]  G. Reaven All obese individuals are not created equal: insulin resistance is the major determinant of cardiovascular disease in overweight/obese individuals , 2005, Diabetes & vascular disease research.

[26]  Remi Rabasa-Lhoret,et al.  The metabolically healthy but obese individual presents a favorable inflammation profile. , 2005, The Journal of clinical endocrinology and metabolism.

[27]  C. Gallou-Kabani,et al.  Nutritional epigenomics of metabolic syndrome: new perspective against the epidemic. , 2005, Diabetes.

[28]  F. Leonetti,et al.  Prevalence of uncomplicated obesity in an Italian obese population. , 2005, Obesity research.

[29]  H. Lamb,et al.  The association between abdominal visceral fat and carotid stiffness is mediated by circulating inflammatory markers in uncomplicated type 2 diabetes. , 2005, The Journal of clinical endocrinology and metabolism.

[30]  A. Karelis,et al.  Can we identify metabolically healthy but obese individuals (MHO)? , 2004, Diabetes & metabolism.

[31]  R. Ross,et al.  Duration of overweight and metabolic health risk in American men and women. , 2004, Annals of epidemiology.

[32]  C. Lamendola,et al.  Prevalence of insulin resistance and associated cardiovascular disease risk factors among normal weight, overweight, and obese individuals. , 2004, Metabolism: clinical and experimental.

[33]  H. Oflaz,et al.  Determination of endothelial function and early atherosclerotic changes in healthy obese women. , 2003, Diabetes, nutrition & metabolism.

[34]  T. Garland,et al.  Genetic selection of mice for high voluntary wheel running: effect on skeletal muscle glucose uptake. , 2001, Journal of applied physiology.

[35]  E. A. Sims,et al.  What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women? , 2001, The Journal of clinical endocrinology and metabolism.

[36]  R. Hanson,et al.  Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. , 2000, Diabetes.

[37]  S. Reis,et al.  Weight cycling and high-density lipoprotein cholesterol in women: evidence of an adverse effect: a report from the NHLBI-sponsored WISE study. Women's Ischemia Syndrome Evaluation Study Group. , 2000, Journal of the American College of Cardiology.

[38]  D A Follmann,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2000 by The Endocrine Society Quantitative Insulin Sensitivity Check Index: A Simple, Accurate Method for Assessing Insulin Sensitivity In Humans , 2022 .

[39]  G. Colditz,et al.  The disease burden associated with overweight and obesity. , 1999, JAMA.

[40]  M. Thun,et al.  Body-mass index and mortality in a prospective cohort of U.S. adults. , 1999, The New England journal of medicine.

[41]  M. Matsuda,et al.  Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. , 1999, Diabetes care.

[42]  J. Levine,et al.  Role of nonexercise activity thermogenesis in resistance to fat gain in humans. , 1999, Science.

[43]  S. Kiechl,et al.  Prevalence of insulin resistance in metabolic disorders: the Bruneck Study. , 1998, Diabetes.

[44]  E. Ferrannini,et al.  Influence of duration of obesity on the insulin resistance of obese non-diabetic patients , 1998, International Journal of Obesity.

[45]  E. Ferrannini,et al.  Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR). , 1997, The Journal of clinical investigation.

[46]  R. Turner,et al.  Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man , 1985, Diabetologia.

[47]  Manning Feinleib,et al.  Obesity as an Independent Risk Factor for Cardiovascular Disease: A 26‐year Follow‐up of Participants in the Framingham Heart Study , 1983, Circulation.

[48]  G. Shulman,et al.  Metabolic defects in lean nondiabetic offspring of NIDDM parents: a cross-sectional study. , 1997, Diabetes.