Is a nutritional therapeutic approach unsuitable for metabolically healthy but obese women?

Abstract

Metabolically healthy but obese postmenopausal women are a subset of obese individuals who do not show obesityrelated metabolic abnormalities such as insulin resistance, a pro-atherosclerotic lipid profile, a proinflammatory state and hypertension [1,2]. In longitudinal studies, this phenotype was associated with reduced risks of developing type 2 diabetes and cardiovascular disease [3].These 'fit-fat individuals' are of interest because they constitute a model that may provide insight into the pathogenesis of insulin resistance in humans. In addition, they represent a potential clinical challenge in that they may require a different therapeutic strategy from that used to treat obese and insulin-resistant women.With respect to the pathogenic issue, it is presently unclear why these women are protected. Initially, investigators focused on elucidating the mechanism underlying this protective effect, with the aim of identifying potential therapeutic targets for the treatment of obese and insulinresistant individuals. It was reported that a lower visceral fat content, despite a high body fat content, and a lower accumulation of fat within ectopic sites may contribute to the favourable metabolic profile [2,4]. These metabolically healthy but obese postmenopausal women had lower circulating levels of high-sensitivity C-reactive protein compared with 'at-risk' women [5], suggesting that the lack of a systemic proinflammatory condition, common in obesity, may explain the protection. It is also possible that the higher insulin sensitivity may be due to a primary genetic metabolic event that contributes to a protective metabolic profile but at the same time influences the early onset of obesity. This is consistent with a study on Pima Indians showing that insulin sensitivity is a predictor of future obesity [6]. The importance of these distinctive features is confirmed by the profile of metabolically obese but normal-weight women, who are characterised by a diametrically opposite profile. These women have a higher body fat content in spite of a normal BMI, and show the cluster of phenotypic risk factors associated with the insulin resistance syndrome [7,8].With respect to the clinical relevance of metabolically healthy but obese women, in this issue of Diabetologia, Karelis et al. [9] report the original finding that these women may respond differently to an energy-restricted diet than insulin-resistant obese women. From an original population of 121 obese women recruited for a weight loss programme, the authors present data on two selected subgroups of women: those within the upper quartile (the metabolically healthy but obese postmenopausal women) and those within the lower quartile (insulin-resistant and 'at-risk' individuals) of insulin sensitivity values as assessed by means of the euglycaemic-hyperinsulinaemic clamp. The clamp was performed before and after the Diabetologia

Hypocaloric Diet and Regular Moderate Aerobic Exercise Is an Effective Strategy to Reduce Anthropometric Parameters and Oxidative Stress in Obese Patients

“…These findings are in line with those showing that excess fat is involved in the generation of oxidative stress [30]. Even if it has been suggested that physical exercise rather than an energy-restricted diet could be recommended as an essential method for body weight reduction [31,32], in this work we showed that the protective benefit generated by HD treatment could be reinforced by regular moderate aerobic exercise. This benefit could to be related to an induction of antioxidant enzymes.…”

Effects of a lifestyle intervention in metabolically benign and malign obesity

“…All three studies showed an improvement in cardiovascular risk profile in OIR, but not in MHO, women, despite similar weight loss [8][9][10]. In view of these findings and the limited healthcare resources, the necessity and the benefit of a lifestyle intervention in MHO individuals has been questioned [11,12]. On the other hand, while OIR individuals clearly benefit from the lifestyle intervention [8][9][10], it is important to know whether this effect is sufficient to place them in a position where protection from obesity-related metabolic consequences is expected.…”

A Weight Loss Diet Intervention Has a Similar Beneficial Effect on Both Metabolically Abnormal Obese and Metabolically Healthy but Obese Premenopausal Women

“…It has indeed been suggested that weight loss in postmenopausal MHO women may be unnecessary and paradoxically harmful given the favorable metabolic profile of these individuals [18]. Whether these findings also apply to premenopausal obese women remains to be investigated [14]. …”

“…Intervention studies investigating the effect of weight loss on cardiometabolic risk factors in MHO individuals have yielded contradictory results, and the question of whether weight loss is also a priority in MHO individuals is still under debate [2,14]. Evangelou et al [15] reported that MHO individuals showed lower reduction in their body weight after a 3-month low-fat diet plus weight-reducing drugs compared with a 6 years older group of obese and overweight patients with metabolic syndrome, whereas Kantartzis et al [16] showed similar body weight reductions in both MHO individuals and an obese group of men and women with insulin resistance after a 9-month lifestyle intervention program.…”