R. Rabasa-Lhoret

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.

Diabetes : a major co-morbidity of cystic fibrosis

Cystic fibrosis-related diabetes (CFRD) is a frequent complication of cystic fibrosis, its prevalence increases with age of patient and is close to 30% at the age of 30 years. As life expectancy greatly increases, the number of cystic fibrosis patients developing diabetes will increase too. CFRD shares some features with type 1 and type 2 diabetes, initial phase is characterised by postprandial hyperglycaemia followed by a progression toward insulin deficiency. Insulin deficiency is an essential factor in the development of diabetes with an additional contribution of insulin resistance. Systematic screening with an oral glucose tolerance test is recommended from the age of 14 years because clinical signs of CFRD are often confused with signs of pulmonary infection and CFRD occurrence is associated with weight and pulmonary function deterioration. In observational studies CFRD diagnosis is associated with a significant increase in mortality, while treatment allow correction of weight and lung deterioration suggesting that CFRD has a significant impact on CF evolution. Microvascular complications are recognised, although paucity of data does not permit a clear description of their natural history. Annual screening for microvascular complication is recommended. There is no evidence by now that CF patients develop macrovascular complications. The only recommended pharmacological treatment is insulin therapy.

How can we measure insulin sensitivity/resistance?

Insulin resistance represents a major public health problem, as it plays a major role in the pathophysiology of type 2 diabetes mellitus; it is also associated with increased cardiovascular risk and atherogenic dyslipidaemia, and is a central component of the cluster of metabolic abnormalities that comprise the metabolic syndrome. Thus, the development of tools to quantify insulin sensitivity/resistance has been the main objective of a number of studies. Insulin resistance can be estimated with the use of several biological measurements that evaluate different aspects of this complex situation. To that end, it requires various resources, ranging from just a single fasting blood sample for simple indices, such as the HOMA or QUICKI, to a research setting in which to perform the gold-standard hyperinsulinaemic-euglycaemic clamp test. The choice of method for evaluating insulin resistance depends on the nature of the information required (classification of individual subjects, group comparisons, precise measurement of either global, muscle or liver insulin sensitivity/resistance) and on the available resources. The aim of this review is to analyze the most frequently used assay methods in an attempt to evaluate when and why these methods may be useful.

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.

Nutritional intervention to reduce the n −6/ n −3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy subjects

Background/Objectives:Consumption of n−3 polyunsaturated fatty acids (PUFA) has a favourable impact on inflammation and cardiovascular disease. However, the Western diet is characterized by a low n−3 PUFA intake and an imbalance in the n−6/n−3 PUFA ratio. Study the effect 10-week of diet modification to decrease the n−6/n−3 PUFA ratio on cardiovascular risk factors and resting energy expenditure.Subjects and methods:Ten-week dietary intervention in 17 healthy subjects. Dietary intake, euglycemic hyperinsulinemic clamp, indirect calorimetry, lipid profile, hormones, inflammatory markers and erythrocyte membrane fatty acid composition were recorded before and at the end of the intervention. Comparisons are between baseline and post-treatment levels.Results:Dietary records of the linoleic acid/α-linolenic acid ratio (baseline: 32.2 (s.d. 3.7) vs post-intervention: 2.2 (s.d. 0.1), P<0.0001) and erythrocyte membrane fatty acid composition reflected good compliance. Dietary intervention was associated with significant reductions in TNF-α (baseline: 2.2 (s.d. 0.3), post-intervention: 1.5 (s.d. 0.3) pg/ml, P=0.01) and low-density lipoprotein-cholesterol (baseline: 2.5 (s.d. 0.2), post-intervention: 2.3 (s.d. 0.1) mmol/l, P=0.03) and increased adiponectin (baseline: 6.5 (s.d. 0.7), post-intervention: 7.6 (s.d. 0.6) μg/ml, P=0.02). Fasting lipid oxidation was increased (baseline: 0.7 (s.d. 0.1), post-intervention: 0.9 (s.d. 0.1) mg/kg.min, P=0.01), whereas glucose oxidation decreased in both fasting (baseline: 1.6 (s.d. 0.1), post-intervention: 1.3 (s.d. 0.1) mg/kg.min, P=0.02) and hyperinsulinaemic conditions (baseline: 3.6 (s.d. 0.1), post-intervention: 3.3 (s.d. 0.1) mg/kg.min, P=0.04). Insulin sensitivity was not affected by the intervention.Conclusion:A decreased n−6/n−3 PUFA ratio can be achieved with simple dietary counselling, resulting in multiple, potentially favourable effects on the metabolic and inflammatory profiles.

No relationship between mean plasma glucose and glycated haemoglobin in patients with cystic fibrosis-related diabetes

AIM Cystic fibrosis-related diabetes (CFRD) prevalence has increased dramatically with the improved life expectancy of patients with cystic fibrosis (CF). Glycated haemoglobin (HbA(1c)) is an important tool for monitoring blood glucose control but, unlike in type 1 and type 2 diabetes, a correlation between HbA(1c), fructosamine and mean plasma glucose has not been clearly established in CF. This study aimed to examine the relationship between mean plasma glucose and HbA(1c) or fructosamine in stable patients with CFRD. METHODS Fifteen type 1 diabetes and 13 CFRD patients (HbA(1c)<9.0%; no anaemia), matched for age and body mass index (BMI), provided 72 capillary blood glucose profiles taken 3days/month for three months. At the end of this time, HbA(1c) and fructosamine were measured. Mean plasma glucose was estimated using the Diabetes Control and Complications Trial (DCCT) conversion formula, and linear regressions carried out to establish its relationship with HbA(1c) and fructosamine. RESULTS In type 1 diabetes patients, mean plasma glucose correlated significantly with HbA(1c) (r=0.68; P=0.005). In CFRD patients, no correlation was found between mean plasma glucose and HbA(1c) (r=0.24; P=0.460). Also, no association was found between mean plasma glucose, representing the month before blood sampling, and fructosamine in either group. CONCLUSION Unlike in type 1 diabetes, HbA(1c) did not correlate with mean plasma glucose in CFRD subjects. Thus, having a normal HbA(1c) may not be sufficient to indicate a low risk of diabetes complications in CFRD. Further studies are required to explain such a discrepancy.

Lifestyle behaviours and components of energy balance as independent predictors of ghrelin and adiponectin in young non-obese women

AIM Dysregulation of the normal levels of ghrelin, leptin and adiponectin in young non-obese subjects could promote food intake, diabetes and cardiovascular disease in later stages of life. Little information is available on how plasmatic concentrations of these hormones may be influenced by eating habits and/or components of energy balance in a young population, which if known, could facilitate their voluntary regulation. METHODS In this cross-sectional study we examined the predictors of fasting plasma ghrelin, adiponectin and leptin in a population of well-characterized young non-obese women (N = 63). Energy intake was assessed by 24-hour dietary recall, resting metabolic rate (RMR) by indirect calorimetry, physical activity energy expenditure (PAEE) by tri-axial accelerometer, physical fitness by VO(2 peak), and eating behaviors by self administrated questionnaire. RESULTS Lower RMR and higher HDL-cholesterol were independent predictors of higher plasma ghrelin explaining 17.6% of its variation even after correcting for BMI. Higher total or central fat mass was the only predictor of higher plasma leptin, and no other variable added any power to the prediction equation. Finally, higher energy intake and waist circumference and lower PAEE predicted lower plasma adiponectin in young non-obese women, explaining 43% of the variation in its concentrations even after correcting for total or central fat mass. CONCLUSION Components of the energy balance (ie: energy intake and/or expenditure) influence adiponectin and ghrelin circulating levels. That is, higher energy intake and lower physical activity independently predict lower adiponectin concentrations, whereas lower resting metabolic rate independently predicts higher ghrelin levels in young non-obese women. Prospective studies are needed to examine whether circulating concentrations of ghrelin and adiponectin can be voluntarily regulated by lifestyle interventions.

Anthropometric, metabolic, dietary and psychosocial profiles of underreporters of energy intake: a doubly labeled water study among overweight/obese postmenopausal women--a Montreal Ottawa New Emerging Team study.

Background/Objectives:To analyze the anthropometric, metabolic, psychosocial and dietary profiles of underreporters, identified by the doubly labeled water technique, in a well-characterized population of overweight and obese postmenopausal women.Subjects/Methods:The study population consisted of 87 overweight and obese sedentary postmenopausal women (age: 57.7±4.8 years, body mass index: 32.4±4.6 kg/m2). Subjects were identified as underreporters based on the energy intake to energy expenditure ratio of <0.80. We measured (1) body composition (by dual-energy X-ray absorptiometry), (2) visceral fat (by computed tomography), (3) blood profile, (4) resting blood pressure, (5) peak oxygen consumption (VO2 peak), (6) total energy expenditure, (7) muscle strength and (8) psychosocial and dietary profiles.Results:Out of 87 subjects, 50 (57.5%) were identified as underreporting subjects in our cohort. Underreporters showed higher levels of body mass index, fat mass, visceral fat, hsC-reactive protein, perceived stress and percentage of energy from protein, as well as lower levels of VO2 peak, dietary intake of calcium, fiber, iron, vitamin B-1 and 6, as well as servings of fruit and vegetables. Logistic regression analysis showed that fat mass, odd ratio 1.068 (95% confidence interval 1.009–1.130) and perceived stress, odd ratio 1.084 (95% confidence interval 1.011–1.162) were independent characteristics of underreporters.Conclusions:Results from this study show significant differences in anthropometric, metabolic, psychosocial and dietary profiles between underreporters and non-underreporters in our cohort of overweight and obese postmenopausal women.

Metabolic profile and quality of life in class I sarcopenic overweight and obese postmenopausal women: a MONET study.

Sarcopenia is believed to be associated with disability and metabolic complications. The objective of this study was to examine the metabolic and quality-of-life profile of sarcopenic overweight and obese postmenopausal women. In this cross-sectional study of 136 healthy overweight and obese postmenopausal women, 9 class I sarcopenic women were identified. Class I sarcopenia was defined as an appendicular lean body mass index (ALBMI) <or= 6.44 kg.m(-2) (appendicular lean body mass/height). Outcome measures were body composition (dual energy X-ray absorptiometry and computed tomography), blood lipids, inflammation markers, blood pressure, insulin sensitivity (homeostasis model assessment and hyperinsulinemic-euglycemic clamp), cardiorespiratory fitness, and quality of life (Medical Outcomes Study General Health Survey questionnaire). By design, class I sarcopenic women (n = 9) had a significantly lower ALBMI and appendicular lean body mass than nonsarcopenic women (n = 127). In addition, class I sarcopenic women tended to have lower levels of insulin resistance (p = 0.070) and fasting glucose (p = 0.054). However, no difference between the groups was observed for quality of life. This study showed that, in our sample of class I sarcopenic overweight and obese postmenopausal women, subjects did not present an unfavourable metabolic or quality-of-life profile, compared with nonsarcopenic overweight and obese postmenopausal women.

Association of insulin sensitivity and muscle strength in overweight and obese sedentary postmenopausal women

The objective of this study was to examine the relationship between insulin sensitivity and lower body muscle strength in overweight and obese sedentary postmenopausal women. The design of the study was cross-sectional. The study population consisted of 82 non-diabetic overweight and obese sedentary postmenopausal women (age: 58.2 +/- 5.1 y; body mass index (BMI): 32.4 +/- 4.6 kg.m-2). Subjects were classified by dividing the entire cohort into quartiles based on relative insulin sensitivity expressed per kilograms of lean body mass (LBM) (Q1, < 10.3, vs. Q2, 10.3-12.4, vs. Q3, 12.5-14.0, vs. Q4, >14.0 mg.min-1.kg LBM-1). We measured insulin sensitivity (using the hyperinsulinemic-euglycemic clamp technique), body composition (using dual-energy X-ray absorptiometry), visceral fat and muscle attenuation (using computed tomography), and a lower-body muscle strength index expressed as weight lifted in kilograms per kilogram of LBM (kg.kg LBM-1) (using weight-training equipment). A positive and significant relationship was observed between insulin sensitivity and the muscle strength index (r = 0.37; p < 0.001). Moreover, a moderate but significant correlation was observed between the muscle strength index and muscle attenuation (r = 0.22; p < 0.05). Finally, the muscle strength index was significantly higher in the Q4 group compared with the Q2 and Q1 groups, respectively (3.78 +/- 1.13 vs. 2.99 +/- 0.77 and 2.93 +/- 0.91 kg.kg LBM-1; p < 0.05). Insulin sensitivity is positively associated with lower-body muscle strength in overweight and obese sedentary postmenopausal women.