Martin Brochu

Characterizing the profile of obese patients who are metabolically healthy

The presence of obesity-related metabolic disturbances varies widely among obese individuals. Accordingly, a unique subset of obese individuals has been described in the medical literature, which seems to be protected or more resistant to the development of metabolic abnormalities associated with obesity. These individuals, now known as ‘metabolically healthy but obese’ (MHO), despite having excessive body fatness, display a favorable metabolic profile characterized by high levels of insulin sensitivity, no hypertension as well as a favorable lipid, inflammation, hormonal, liver enzyme and immune profile. However, recent studies have indicated that this healthier metabolic profile may not translate into a lower risk for mortality. Mechanisms that could explain the favorable metabolic profile of MHO individuals are poorly understood. However, preliminary evidence suggests that differences in visceral fat accumulation, birth weight, adipose cell size and gene expression-encoding markers of adipose cell differentiation may favor the development of the MHO phenotype. Despite the uncertainty regarding the exact degree of protection related to the MHO status, identification of underlying factors and mechanisms associated with this phenotype will eventually be invaluable in helping us understand factors that predispose, delay or protect obese individuals from metabolic disturbances. Collectively, a greater understanding of the MHO individual has important implications for therapeutic decision making, the characterization of subjects in research protocols and medical education.

Sarcopenic/Obesity and Physical Capacity in Older Men and Women: Data From the Nutrition as a Determinant of Successful Aging (NuAge)—the Quebec Longitudinal Study

Sarcopenia and obesity have been independently associated with physical capacity impairments. However, few studies have investigated the impact of sarcopenic/obesity on physical capacity in older individuals using objective measures of physical capacity and body composition. This study included 904 older individuals aged between 68 and 82 years old. Body composition (fat mass (FM) and lean body mass (LBM) by dual‐energy X‐ray absorptiometry (DXA)), physical capacity (timed up and go, chair stands, walking speed at normal and fastest pace, and one leg stand), sum of reported chronic conditions and physical activity level were measured. A global physical capacity score was then calculated giving a maximal score of 20. Finally, four groups were created within genders based on sarcopenia and obesity ((i) nonsarcopenic/nonobese; (ii) sarcopenic/nonobese; (iii) nonsarcopenic/obese; (iv) sarcopenic/obese). The four groups were significantly different for the sit‐to‐stand test and the one leg stand test (P < 0.05) and only for the one leg stand test in women (P < 0.05). In both genders results for the global physical capacity score revealed that both obese groups (sarcopenic and nonsarcopenic) were similar (P = 0.14 in men and P = 0.19 in women) and had a lower global physical capacity score compared to nonsarcopenic/nonobese individuals (P < 0.05). In addition, sarcopenic women displayed a higher score than both obese nonsarcopenic and obese sarcopenic groups (P < 0.01). Sarcopenic/obese men and women do not display lower physical capacity compared to nonsarcopenic/obese individuals in this cohort of well‐functioning older men and women. Obesity per se appears to contribute more to lower physical capacity than sarcopenia.

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

To the Editor: A unique subset of obese individuals has been identified that appears to be protected against obesityrelated metabolic disturbances [1, 2]. These individuals, now known as ‘metabolically healthy but obese’ (MHO) individuals, display a favourable metabolic profile, characterised by high levels of insulin sensitivity, normal lipid and inflammation profiles and no sign of hypertension, despite having excessive body fatness. In fact, the metabolic profiles of MHO postmenopausal women are virtually indistinguishable from those of young lean women [3]. Interestingly, a recent longitudinal study reported that the protective metabolic profile observed in MHO individuals was associated with lower incidences of type 2 diabetes and cardiovascular diseases [4]. Moreover, evidence suggests that MHO individuals may account for as much as 20–30% of the obese population [5]. An important question that seems to be unresolved is whether MHO individuals would gain any metabolic benefit from weight loss. Indeed, several studies have shown that weight loss improves insulin sensitivity and metabolic abnormalities and reduces the risk for type 2 diabetes in obese individuals [6, 7]. However, attempts to achieve weight loss in MHO individuals, by way of diet, may be actually counterproductive and potentially harmful. One may even question the need to aggressively treat MHO individuals given their favourable metabolic profile. Therefore, the aim of the present study was to investigate the effect of a 6 month energy-restricted diet on insulin sensitivity using the euglycaemic–hyperinsulinaemic clamp technique in a sample of MHO postmenopausal women. This study was approved by the ethics committee of the University of Montreal. After reading and signing the consent form, each participant was invited to the Metabolic Unit for testing. The women then entered a medically supervised 6 month weight loss programme, which aimed to reduce body weight by 10%. To achieve a level of energy restriction, the baseline resting metabolic rate was extrapolated over a 24 h period (kcal/min×1,440 min) and multiplied by an activity factor of 1.4, which corresponds to a sedentary state. Thereafter, instructions on how to follow a hypoenergetic diet Diabetologia (2008) 51:1752–1754 DOI 10.1007/s00125-008-1038-4

Resistance training on physical performance in disabled older female cardiac patients

PURPOSE We evaluated the value of resistance training on measures of physical performance in disabled older women with coronary heart disease (CHD). METHODS The study intervention consisted of a 6-month program of resistance training in a randomized controlled trial format. Training intensity was at 80% of the single-repetition maximal lift. Control patients performed light yoga and breathing exercises. Study participants included 42 women with CHD, all >or= 65 yr of age and community dwelling. Subjects were screened by questionnaire to have low self-reported physical function. The primary study measurements related to the performance of 16 household activities of the Continuous Scale Physical Functional Performance test (CSPFP). These ranged from dressing, to kitchen and cleaning activities, to carrying groceries and walking onto a bus with luggage, and a 6-min walk. Activities were measured in time to complete a task, weight carried during a task, or distance walked. Other measures included body composition, measures of aerobic fitness and strength, and questionnaire-based measures of physical function and depression score. RESULTS Study groups were similar at baseline by age, aerobic capacity, strength, body composition, and in performing the CSPFP. After conditioning, 13 of 16 measured activities were performed more rapidly, or with increased weight carried, compared with the control group (all P < 0.05). Maximal power for activities that involved weight-bearing over a distance, increased by 40% (P < 0.05). CONCLUSIONS Disabled older women with CHD who participate in an intense resistance-training program improve physical capacity over a wide range of household physical activities. Benefits extend beyond strength-related activities, as endurance, balance, coordination, and flexibility all improved. Strength training should be considered an important component in the rehabilitation of older women with CHD.

Identifying metabolically healthy but obese individuals in sedentary postmenopausal women.

The purpose of this study was to compare different methods to identify metabolically healthy but obese (MHO) individuals in a cohort of obese postmenopausal women. We examined the anthropometric and metabolic characteristics of 113 obese (age: 57.3 ± 4.8 years; BMI: 34.2 ± 2.7 kg/m2), sedentary postmenopausal women. The following methods were used to identify MHO subjects: the hyperinsulinemic–euglycemic clamp (MHO: upper quartile of glucose disposal rates); the Matsuda index (MHO: upper quartile of the Matsuda index); the homeostasis model assessment (HOMA) index (MHO: lower quartile of the HOMA index); having 0–1 cardiometabolic abnormalities (systolic/diastolic blood pressure ≥130/85 mm Hg, triglycerides (TG) ≥1.7 mmol/l, glucose ≥5.6 mmol/l, HOMA >5.13, high‐sensitive C‐reactive protein (hsCRP) >0.1 mg/l, high‐density lipoprotein‐cholesterol (HDL‐C) <1.3 mmol/l); and meeting four out of five metabolic factors (HOMA ≤2.7, TG ≤1.7 mmol/l, HDL‐C ≥1.3 mmol/l, low‐density lipoprotein‐cholesterol ≤2.6 mmol/l, hsCRP ≤3.0 mg/l). Thereafter, we measured insulin sensitivity, body composition (dual‐energy X‐ray absorptiometry), body fat distribution (computed tomography scan), energy expenditure, plasma lipids, inflammation markers, resting blood pressure, and cardiorespiratory fitness. We found significant differences in body composition (i.e., peripheral fat mass, central lean body mass (LBM)) and metabolic risk factors (i.e., HDL‐C, hsCRP) between MHO and at risk individuals using the different methods to identify both groups. In addition, significant differences between MHO subjects using the different methods to identify MHO individuals were observed such as age, TG/HDL, hsCRP, and fasting insulin. However, independently of the methods used, we noted some recurrent characteristics that identify MHO subjects such as TG, apolipoprotein B, and ferritin. In conclusion, the present study shows variations in body composition and metabolic profile based on the methods studied to define the MHO phenotype. Therefore, an expert consensus may be needed to standardize the identification of MHO individuals.

Metabolically healthy but obese individuals: relationship with hepatic enzymes

The purpose of this study was to investigate the level of plasma hepatic enzymes in obese women displaying the metabolically healthy but obese (MHO) phenotype. We studied 104 obese, sedentary, postmenopausal women. Subjects were classified as MHO or at risk based on insulin sensitivity as assessed with the oral glucose tolerance test-derived Matsuda index. Subjects were divided into quartiles according to insulin sensitivity values. Subjects in the upper quartile were categorized as MHO, whereas subjects in the lower 3 quartiles represented at-risk subjects. Outcome measures were hepatic enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, and gamma-glutamyltransferase [GGT]], high-density lipoprotein cholesterol, triglycerides, triglycerides to high-density lipoprotein cholesterol ratio, apolipoprotein B, fatty liver index, body composition (dual-energy x-ray absorptiometry), and visceral adipose tissue (computed tomography). The MHO individuals had significantly lower concentrations of ALT, AST, and GGT as well as a lower fatty liver index compared with at-risk subjects (P < .05). In addition, lean body mass index and visceral adipose tissue were significantly lower in MHO individuals (P < .05). Moreover, stepwise regression analysis showed that ALT explained 17.9% of the variation in insulin sensitivity in our cohort, which accounted for the greatest source of unique variance. Results of the present study indicate that postmenopausal women displaying the MHO phenotype present favorable levels of ALT, AST, and GGT. Lower concentrations of hepatic enzymes, in particular, lower circulating ALT levels, in MHO individuals may reflect lower hepatic insulin resistance and lower liver fat content; and this could be involved, at least in part, in the protective profile of MHO individuals.

Effects of Home Versus Supervised Exercise for Patients With Intermittent Claudication

PURPOSE This study was performed to test the efficacy of a supervised, hospital-based exercise program compared with a home-based exercise program involving minimal supervision, for both walking ability and quality of life measures in patients with exercise-limiting intermittent leg claudication. METHODS Twenty-one patients were assigned randomly to 12 weeks of supervised exercise or to a home-based exercise group. After 12 weeks the participants in the supervised group transitioned to a home-based program. Both groups were then reevaluated at the end of 24 weeks. The initial claudication distance (ICD) and absolute claudication distance (ACD) on progressive treadmill exercise was measured at baseline, 12 weeks, and 24 weeks. Additionally, self-reported quality of life status was evaluated using the MOS SF-36 questionnaire. RESULTS Each group improved (P < 0.01) ACD from baseline to 12 weeks, which was sustained at the 24-week follow-up. Both groups experienced similar long-term improvements (P < 0.05) in ACD (521.5 +/- 253.4 meters to 741.9 +/- 365.6 meters for the supervised group, 532.2 +/- 263.5 meters to 715.0 +/- 394.4 meters in the home group, P not significant, between groups). The supervised group experienced a greater improvement (P < 0.01) in the ICD after 12 weeks than the home group but not at 24 weeks. The on-site group also experienced significant improvements in ICD after 24 weeks (P < 0.05). Neither group manifested an improvement in self-reported physical function or mental health as assessed by the MOS SF-36. CONCLUSION A structured exercise program was more effective in improving the ICD over a 24-week period than a less formal, home-based program. However, if patients are screened properly and receive adequate instruction, a home-based program can be a safe, low-cost alternative providing similar long-term (24 weeks) exercise benefits in ACD.

Obesity, body fat distribution, and coronary artery disease.

Obesity is an independent risk factor for the development of coronary artery disease (CAD). Obesity also increases risk for CAD indirectly through its association with insulin resistance, hyperlipidemia, and hypertension. An increased accumulation of fat in the intraabdominal cavity, termed visceral adiposity, is highly correlated with an adverse coronary risk profile. In patients at risk for coronary artery disease, the treatment of obesity results in an improved coronary risk profile. The prevalence of obesity is extremely high in coronary populations, yet the effect of weight loss on cardiovascular outcomes in CAD patients has received relatively little attention. Observational studies in the cardiac rehabilitation setting showed that patients who lose weight and exercise show an improvement in coronary risk profile. Further research is needed to better define the clinical effectiveness of weight loss programs and their benefits in coronary patients.

Resistance Training Does Not Contribute to Improving the Metabolic Profile after a 6-Month Weight Loss Program in Overweight and Obese Postmenopausal Women

CONTEXT Limited data are available regarding the impact of caloric restriction (CR) in combination with resistance training (RT) on the metabolic profile of postmenopausal women. OBJECTIVE The objective of the study was to determine whether RT adds to CR in improving body composition and the metabolic profile. DESIGN AND SETTING This was a 6-month, randomized, clinical trial. PATIENTS Patients included 107 postmenopausal women (body mass index >27 kg/m(2)). INTERVENTION The intervention was a 6-month CR alone or in combination with a RT program. MAIN OUTCOME MEASURES Fat mass (FM), lean body mass (LBM), abdominal sc fat and visceral fat, fasting lipids, insulin sensitivity, resting blood pressure, and inflammation markers were measured. RESULTS Both groups were similar at baseline and significantly decreased body weight, body mass index, FM, percent FM, abdominal sc fat, and visceral fat after the study (P < 0.001), with greater losses of percent FM and trunk FM in the CR + RT group (P < 0.05). LMB significantly decreased in the CR (-0.9 +/- 2.4 kg) and the CR+RT (-0.4 +/- 2.2 kg) groups (P < 0.005), with no difference between them. Both groups significantly improved plasma triglycerides, fasting insulin level, glucose disposal, and markers of the inflammation profile after weight loss (P < 0.05), with no difference between groups. No improvements were observed for the other variables of interest in both groups. CONCLUSIONS CR+RT was associated with greater losses in percent FM and trunk FM compared with CR alone. However, CR+RT was not associated with additional improvements in the metabolic profile compared with CR alone.

The effect of the menopausal transition on body composition and cardiometabolic risk factors: a Montreal-Ottawa New Emerging Team group study

Objective Cardiovascular disease is the first cause of mortality in women in North America. The risk of cardiovascular disease increases sharply after middle age in women, especially after menopause. The aim was to investigate changes in body composition and cardiometabolic profile throughout the menopausal transition. Methods This was a 5-year observational, longitudinal study on the menopausal transition. The study included 102 premenopausal women at baseline (age, 49.9 ± 1.9 y; body mass index, 23.3 ± 2.2 kg/m2). Outcome measures include menopause status, body composition by dual-energy x-ray absorptiometry (total fat mass [FM], trunk FM, and total fat-free mass), waist circumference, visceral and abdominal subcutaneous fat, fasting glucose and insulin levels, homeostasis model assessment of insulin resistance, plasma lipid levels (triglycerides, total cholesterol, and high- and low-density lipoprotein cholesterol), and resting blood pressure. Results Repeated-measure analyses revealed significant increases for FM, percentage FM, trunk FM, visceral fat, plasma fasting glucose, and high-density lipoprotein cholesterol (0.05 > P < 0.01) and a significant decrease for plasma glucose levels after follow-up. Those who were in perimenopause or postmenopause by year 3 of the study showed a significant increase in visceral fat (P < 0.01) compared with baseline. Despite some significant changes in the metabolic profile among the menopause statuses, the women did not show any cardiometabolic deterioration by the end of the study. Conclusions Our results suggest that changes in body composition and fat distribution can occur in nonobese women as they go through the menopausal transition. However, these changes were not accompanied by cardiometabolic deteriorations in the present study.