Metabolically healthy but obese women: effect of an energy-restricted diet

Karelis, Antony D.; Messier, Virginie; Brochu, Martin; Rabasa‐Lhoret, Rémi

doi:10.1007/s00125-008-1038-4

Cited by 149 publications

(145 citation statements)

References 7 publications

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“…46 In addition, CR has been shown to significantly improve IS in previously obese, diabetic subjects. 2,47 Coming from a pathological state of IR, which might be comparable to the acute OF in the present study, CR thus seems to have favorable effects on glucose metabolism.…”

Section: Discussionsupporting

confidence: 56%

Effects of brief perturbations in energy balance on indices of glucose homeostasis in healthy lean men

et al. 2011

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BACKGROUND:Little is known about the effects of short-term caloric restriction (CR) and overfeeding (OF) on glucose homeostasis in healthy lean individuals. In addition, it remains unclear whether the effects of CR and OF are reversed by a complementary feeding period. METHODS: Ten healthy men participated in two cycles of controlled 7-day periods of CR and refeeding (RF; protocol A), and OF and CR (protocol B) at ±60% energy requirement. At baseline, insulin sensitivity (IS) was assessed by euglycemic clamp (M). Before and during each feeding cycle, fasting and oral glucose tolerance test-derived indices were used to estimate glucose tolerance, IS and glucose-stimulated insulin secretion. RESULTS: Clamp tests revealed normal IS at baseline (M-values 9.4 ± 2.1 mg kg À1 min À1 , coefficient of variation (CV) inter 22%). M-values were significantly correlated with indices of IS. In protocol A, CR-induced weight loss (À3.0±0.4 kg) was associated with an increase in fasting IS. Postprandial IS and glucose-stimulated insulin secretion remained unchanged, but glucose tolerance decreased. RF decreased fasting and postprandial IS at increased glucose-stimulated insulin secretion. In protocol B, OF significantly increased the body weight ( þ 1.6±0.9 kg). Concomitantly, fasting and postprandial IS decreased at increased glucose-stimulated insulin secretion. Subsequent CR reversed these effects. Inter-individual variability in indices of glucose metabolism was high with coefficients of variation ranging from 9 to 59%. CONCLUSION: Significant changes in glucose metabolism are evident within 7-day periods of controlled OF and underfeeding. Although IS was impaired at the end of the CR --RF cycle, IS was normalized after the OF --CR cycle. At different feeding regimens, homeostatic responses of glucose metabolism were highly variable. Keywords: insulin secretion; insulin sensitivity; glucose homeostasis; weight gain; energy balance INTRODUCTION Long-term perturbations in energy balance, either by overfeeding (OF) or underfeeding, are known to modulate insulin sensitivity (IS). Chronic OF and obesity are commonly characterized by insulin resistance, 1 which has been shown to be completely 2 or partially reversed by acute caloric restriction (CR), as well as by moderate weight loss. 3 --5 On the other hand, IS is preserved or even improved with chronic CR in patients with anorexia nervosa and returned to normal values at the end of refeeding (RF). 6 Although considerable research has been devoted to individuals outside the normal range of body weight, there are only few studies examining the effects of short-term controlled perturbations in energy balance on IS in lean subjects without confounding metabolic abnormalities. 7 --17 Moreover, these studies provide discordant findings that may depend on duration and degree of energy imbalance and macronutrient composition of the diets. Fasting (1 --3 days) consistently caused a decline in IS assessed by clamp-and intravenous glucose tolerance test. 7,8,17 Studies with less severe ...

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Section: Discussionsupporting

confidence: 56%

Effects of brief perturbations in energy balance on indices of glucose homeostasis in healthy lean men

et al. 2011

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“…In conclusion, the study by Karelis et al [9] confirms the effectiveness of an energy-restricted diet for improving whole body insulin sensitivity in association with small reductions in body fat. Interestingly, it also shows that there is a subset of individuals, the most insulin sensitive, that is non-responsive to this treatment and may potentially have a detrimental response.…”

mentioning

confidence: 59%

“…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.…”

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confidence: 99%

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

Perseghin

2008

Diabetologia

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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

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“…Data about the effects of lifestyle modifications specifically in MHO and OIR populations are sparse: two small studies implemented energy-restriction diets for 12 weeks and 6 months in women [8,9], and one a 6 month exercise intervention programme, also in women [10]. 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].…”

Section: Introductionmentioning

confidence: 99%

Effects of a lifestyle intervention in metabolically benign and malign obesity

et al. 2010

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Aims/hypothesis We and others recently characterised metabolically benign or healthy obesity (MHO). In the present study we investigated whether a lifestyle intervention is sufficient to place obese insulin-resistant (OIR) individuals in a position where the possible metabolic consequences are similar to those for MHO individuals. Methods A total of 262 non-diabetic individuals participated in a 9 month lifestyle intervention programme. Obese individuals (BMI≥30.0 kg/m 2 ) were stratified, based on their insulin sensitivity (IS) estimated from an OGTT, into MHO (IS in the upper quartile, n=26) and OIR (IS in the lower three quartiles, n=77). Total body and visceral fat were measured by magnetic resonance (MR) tomography and liver fat by 1 H-MR spectroscopy. Results During the intervention, visceral fat decreased significantly in both groups (both p≤0.009), whereas total body and liver fat decreased only in the OIR group (p< 0.0001; MHO p=0.12 for total body fat and p=0.47 for liver fat). IS improved in the OIR group (p<0.0001), but remained essentially unchanged in the MHO group (p= 0.30). However, despite the significant increase in the OIR group, IS at follow-up barely exceeded 50% of the IS of the MHO group (OIR 9.30±0.53 arbitrary units [AU]; MHO 16.41±1.05 AU; p<0.0001). Conclusions/interpretation IS improves during the lifestyle intervention in OIR individuals. However, it does not reach a level where adequate protection from type 2 diabetes and cardiovascular disease is expected. Thus, stratification of obese individuals based on their metabolic phenotype is important to identify those who are likely to need early pharmacological treatment in addition to the lifestyle intervention.

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Metabolically healthy but obese women: effect of an energy-restricted diet

Cited by 149 publications

References 7 publications

Effects of brief perturbations in energy balance on indices of glucose homeostasis in healthy lean men

Effects of brief perturbations in energy balance on indices of glucose homeostasis in healthy lean men

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

Effects of a lifestyle intervention in metabolically benign and malign obesity

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