Marc-Andre Cornier

Assessing Adiposity: A Scientific Statement From the American Heart Association

The prevalence of obesity in the United States and the world has risen to epidemic/pandemic proportions. This increase has occurred despite great efforts by healthcare providers and consumers alike to improve the health-related behaviors of the population and a tremendous push from the scientific community to better understand the pathophysiology of obesity. This epidemic is all the more concerning given the clear association between excess adiposity and adverse health consequences such as cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The risks associated with overweight/obesity are primarily related to the deposition of adipose tissue, which leads to excess adiposity or body fatness. Furthermore, weight loss, specifically loss of body fat, is associated with improvement in obesity-related comorbidities. Before weight loss interventions can be recommended, however, patients must be assessed for their adiposity-related risk. Unfortunately, healthcare providers and systems have not done a good job of assessing for excess adiposity even in its simplest form, such as measuring body mass index (BMI). It is for these reasons that we must emphasize the importance of assessing adiposity in clinical practices. Although it can be argued that the entire population should be targeted as an important public health issue with a goal of prevention of weight gain and obesity, there are currently so many “at risk” individuals that simple strategies to identify and treat those individuals are necessary. We must identify those individuals at highest risk of comorbidities in order to identify those who might benefit the most from aggressive weight management. This scientific statement will first briefly review the epidemiology of obesity and its related comorbidities, supporting the need for improved assessment of adiposity in daily clinical practice. This will be followed by a discussion of some of the challenges and issues associated with assessing adiposity and then by a review …

Bariatric Surgery and Cardiovascular Risk Factors

The rate of obesity is rising logarithmically, especially in those with severe obesity (body mass index [BMI] >40 kg/m2). Cardiologists, endocrinologists, internists, family practitioners, and most healthcare professionals are increasingly confronted with the severely obese patient and with postoperative bariatric patients because obesity is associated with significant morbidity and increased mortality. In addition, more adolescents these days are severely obese. Substantial long-term successes of lifestyle modifications and drug therapy have been disappointing in this population. The National Institutes of Health has suggested that surgical therapy be proposed to those patients with BMI >40 kg/m2 or >35 kg/m2 with serious obesity-related comorbidities such as systemic hypertension, type 2 diabetes mellitus, and obstructive sleep apnea. When indicated, surgical intervention leads to significant improvements in decreasing excess weight and comorbidities that can be maintained over time. These include diabetes mellitus, dyslipidemia, liver disease, systemic hypertension, obstructive sleep apnea, and cardiovascular dysfunction. Recent prospective, nonrandomized, observational, or case-control population studies have also shown bariatric surgery to prolong survival in the severely obese. Different types of bariatric procedures are being performed. Historically, operative mortality was between 0.1% and 2.0% with more recent data not exceeding 1%. Early complications include pulmonary embolus (0.5%), anastomotic leaks (1.0% to 2.5%), and bleeding (1.0%). Late complications include anastomotic stricture, anastomotic ulcers, hernias, band slippage, and behavioral maladaptation. The number of bariatric operations being performed is increasing tremendously as a result of increasing medical need and the evolution of safer surgical techniques and guidelines. Currently, bariatric surgery should be reserved for patients who have severe obesity in whom efforts at medical therapy have failed and an acceptable operative risk is present. The terms overweight, obese, and severe obesity refer to a clinical continuum. Excess adiposity should be considered a chronic disease that has serious health consequences. An …

The Effects of Overfeeding on the Neuronal Response to Visual Food Cues in Thin and Reduced-Obese Individuals

Background The regulation of energy intake is a complex process involving the integration of homeostatic signals and both internal and external sensory inputs. The objective of this study was to examine the effects of short-term overfeeding on the neuronal response to food-related visual stimuli in individuals prone and resistant to weight gain. Methodology/Principal Findings 22 thin and 19 reduced-obese (RO) individuals were studied. Functional magnetic resonance imaging (fMRI) was performed in the fasted state after two days of eucaloric energy intake and after two days of 30% overfeeding in a counterbalanced design. fMRI was performed while subjects viewed images of foods of high hedonic value and neutral non-food objects. In the eucaloric state, food as compared to non-food images elicited significantly greater activation of insula and inferior visual cortex in thin as compared to RO individuals. Two days of overfeeding led to significant attenuation of not only insula and visual cortex responses but also of hypothalamus response in thin as compared to RO individuals. Conclusions/Significance These findings emphasize the important role of food-related visual cues in ingestive behavior and suggest that there are important phenotypic differences in the interactions between external visual sensory inputs, energy balance status, and brain regions involved in the regulation of energy intake. Furthermore, alterations in the neuronal response to food cues may relate to the propensity to gain weight.

Sex-Based Differences in the Behavioral and Neuronal Responses to Food

Sex-based differences in food intake related behaviors have been observed previously. The objective of this study was to examine sex-based differences in the behavioral and neuronal responses to food. 22 women and 21 men were studied. After 6 days of controlled eucaloric feeding, ad libitum energy intake (EI) was measured for 3 days. Appetite ratings using visual analog scales were obtained before and after each meal. Functional magnetic resonance imaging was performed in the overnight fasted state on the last day of eucaloric feeding while subjects were presented visual stimuli of food and neutral non-food objects. While hunger and prospective consumption were not different between sexes, women had higher post-meal satiety ratings and dietary restraint than men. Images of hedonic foods resulted in significantly greater activation of lateral and dorsolateral prefrontal cortex (DLPFC) and parietal cortex in women as compared to men. No brain regions were more activated in men as compared to women. Men increased their EI during the ad libitum diet phase. While measures of appetite or feeding behaviors did not correlate with either neuronal activation or subsequent EI, DLPFC activation in response to hedonic foods was negatively correlated with EI. In summary, greater prefrontal neuronal responses to food cues in women may suggest increased cognitive processing related to executive function, such as planning, guidance or evaluation of behavior. Finally, increased DLPFC activation, perhaps relating to inhibitory cognitive control in response to food cues may be a better predictor of food intake than behavioral measures.

The Effects of Exercise on the Neuronal Response to Food Cues

Increased physical activity is associated with successful long-term weight loss maintenance due to mechanisms likely more complex than simply increased energy expenditure. The impact of physical activity on the central regulation of food intake may be an important mechanism of this effect. The objective of this study was to examine the effects of exercise training and acute exercise on the neuronal response to food cues as well as eating behaviors. fMRI was performed in the fasted state at baseline and again after a 6 month progressive exercise intervention (supervised, 5 days/wk) both with and without an acute exercise bout in 12 overweight/obese (5 women, 7 men; BMI 33 ± 4 kg/m(2)) healthy adults. fMRI data were acquired while subjects were presented with visual stimuli of foods of high hedonic value as compared to neutral control objects. Questionnaires on eating behaviors, ratings of appeal and desire for foods, and ratings of appetite (hunger, satiety, prospective intake) using visual analog scales were also performed at baseline and again after the 6-month exercise intervention. While only a trend was observed for a reduction in body weight (102 ± 5 to 99 ± 6 kg, p=0.09), a significant reduction in fat mass was observed (36.4 ± 2.8 to 33.7 ± 3.2 kg, p=0.04), although as expected changes in fat mass were variable (-10.0 to +3.7 kg). Chronic exercise was associated with a reduction in the neuronal response to food, primarily in the posterior attention network and insula. A significant positive correlation between the change in fat/body mass and the change in insula response to food cues with chronic exercise was observed. An acute exercise bout attenuated the effects of chronic exercise. The exercise intervention, however, did not impact any of the measures of appetitive behavior. In summary, despite no effects on behavioral measures of appetite, chronic exercise training was associated with attenuation in the response to visual food cues in brain regions known to be important in food intake regulation. The insula, in particular, appears to play an important role in the potential exercise-induced weight loss and weight loss maintenance.

New and emerging weight management strategies for busy ambulatory settings: a scientific statement from the American Heart Association endorsed by the Society of Behavioral Medicine.

Recent data from the Centers for Disease Control and Prevention show that a staggering 68% of American adults are either overweight or obese, and 34% are obese.1 Although there is evidence that its prevalence is stabilizing, obesity remains an extremely serious public health problem. It is a major risk factor for a wide range of medical (eg, type 2 diabetes mellitus), social (eg, discrimination in employment and education settings), and psychological (eg, depression) conditions.2 Although the effectiveness of different obesity treatments has been evaluated systematically,3 rational, safe, and effective treatments from which the majority of overweight and obese patients can benefit remain elusive. New medications are emerging, but their impact on weight loss has been modest, and their long-term adverse effects are uncertain.4 Bariatric surgery is effective but expensive and is appropriate only for a small proportion of patients in whom the benefits outweigh the risks. Effective and safe commercial and noncommercial behavior modification programs are scarce. Changes in public policy and the “built environment”5 may curb obesity, but such changes take a long time to bring about, and the magnitude of their impact has yet to be established clearly. A recent review, for example, concluded that soft drink taxes have only a small impact on a populations average body mass index (BMI).6 It is widely acknowledged that no single strategy will solve the obesity problem and that effective public health initiatives to prevent and treat obesity will require the involvement of multiple stakeholders, including patients, employers, health plans, governments at all levels, the food and beverage industries, and healthcare providers.7,8 Among these healthcare providers are those who deliver care in busy ambulatory settings, including primary care physicians, nurse practitioners, nurses, registered dietitians, and others. Screening and counseling for obesity in …

Effects of short-term overfeeding on hunger, satiety, and energy intake in thin and reduced-obese individuals.

BACKGROUND Certain individuals appear to be resistant to weight gain in an obesigenic environment, yet the mechanisms for this adaptation are unclear. These individuals may sense positive energy balance more appropriately than those individuals prone to weight gain. RESEARCH METHODS AND PROCEDURES Thirteen thin (7 women, 6 men) and 9 reduced-obese (5 women, 4 men) individuals were studied. Measures of intake were obtained using visual analog scales before and after each meal during eucaloric feeding and during three days of 50% overfeeding. Ad libitum energy intake was measured post-overfeeding. RESULTS Overfeeding resulted in a significant reduction in pre-meal hunger in the thin (68+/-6 to 41+/-6 mm, p<0.0001) compared to the reduced-obese individuals (63+/-7 to 65+/-7 mm, p=0.67). There was a significantly greater increase (p=0.0016) in post-meal satiety scores during overfeeding in the thin (65+/-4 to 88+/-4 mm, p<0.0001) compared to the reduced-obese individuals (72+/-5 to 80+/-5 mm, p=0.04). Thin women had a 30% reduction in daily energy intake (1831+/-47 to 1273+/-79 kcal/day, p=0.005) after overfeeding while no difference was seen in the thin men or reduced-obese group. DISCUSSION Thin individuals appear to sense positive energy balance more appropriately with changes in measures of intake than reduced-obese individuals. These findings are especially true in thin women.

New and Emerging Weight Management Strategies for Busy Ambulatory Settings A Scientific Statement From the American Heart Association

Recent data from the Centers for Disease Control and Prevention show that a staggering 68% of American adults are either overweight or obese, and 34% are obese.1 Although there is evidence that its prevalence is stabilizing, obesity remains an extremely serious public health problem. It is a major risk factor for a wide range of medical (eg, type 2 diabetes mellitus), social (eg, discrimination in employment and education settings), and psychological (eg, depression) conditions.2 Although the effectiveness of different obesity treatments has been evaluated systematically,3 rational, safe, and effective treatments from which the majority of overweight and obese patients can benefit remain elusive. New medications are emerging, but their impact on weight loss has been modest, and their long-term adverse effects are uncertain.4 Bariatric surgery is effective but expensive and is appropriate only for a small proportion of patients in whom the benefits outweigh the risks. Effective and safe commercial and noncommercial behavior modification programs are scarce. Changes in public policy and the “built environment”5 may curb obesity, but such changes take a long time to bring about, and the magnitude of their impact has yet to be established clearly. A recent review, for example, concluded that soft drink taxes have only a small impact on a populations average body mass index (BMI).6 It is widely acknowledged that no single strategy will solve the obesity problem and that effective public health initiatives to prevent and treat obesity will require the involvement of multiple stakeholders, including patients, employers, health plans, governments at all levels, the food and beverage industries, and healthcare providers.7,8 Among these healthcare providers are those who deliver care in busy ambulatory settings, including primary care physicians, nurse practitioners, nurses, registered dietitians, and others. Screening and counseling for obesity in …

Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial

Aim To evaluate the effect of alirocumab on frequency of standard apheresis treatments [weekly or every 2 weeks (Q2W)] in heterozygous familial hypercholesterolaemia (HeFH). Methods and results ODYSSEY ESCAPE (NCT02326220) was a double-blind study in 62 HeFH patients undergoing regular weekly or Q2W lipoprotein apheresis. Patients were randomly assigned (2:1, respectively) to receive alirocumab 150 mg (n = 41) or placebo (n = 21) Q2W subcutaneously for 18 weeks. From day 1 to week 6, apheresis rate was fixed according to the patient’s established schedule; from weeks 7 to 18, apheresis rate was adjusted based on the patient’s low-density lipoprotein cholesterol (LDL-C) response in a blinded fashion. Apheresis was not performed when the LDL-C value was ≥30% lower than the baseline (pre-apheresis) value. The primary efficacy endpoint was the rate of apheresis treatments over 12 weeks (weeks 7–18), standardized to number of planned treatments. In the alirocumab group the least square (LS) mean ± SE (95% confidence interval [CI]) per cent change in pre-apheresis LDL-C from baseline at week 6 was −53.7 ± 2.3 (−58.2 to − 49.2) compared with 1.6 ± 3.1 (–4.7 to 7.9) in the placebo group. The primary efficacy endpoint showed statistically significant benefit in favour of alirocumab (Hodges–Lehmann median estimate of treatment difference: 0.75; 95% CI 0.67–0.83; P < 0.0001). Therefore, alirocumab-treated patients had a 0.75 (75%) additional reduction in the standardized rate of apheresis treatments vs. placebo-treated patients. During this period, 63.4% of patients on alirocumab avoided all and 92.7% avoided at least half of the apheresis treatments. Adverse event rates were similar (75.6% of patients on alirocumab vs. 76.2% on placebo). Conclusions Lipoprotein apheresis was discontinued in 63.4% of patients on alirocumab who were previously undergoing regular apheresis, and the rate was at least halved in 92.7% of patients. Alirocumab was generally safe and well tolerated.

Orbitofrontal Cortex Volume and Brain Reward Response in Obesity

Background/objectives:What drives overconsumption of food is poorly understood. Alterations in brain structure and function could contribute to increased food seeking. Recently, brain orbitofrontal cortex (OFC) volume has been implicated in dysregulated eating but little is known how brain structure relates to function.Subjects/methods:We examined obese (n=18, age=28.7±8.3 years) and healthy control women (n=24, age=27.4±6.3 years) using a multimodal brain imaging approach. We applied magnetic resonance and diffusion tensor imaging to study brain gray and white matter volume as well as white matter (WM) integrity, and tested whether orbitofrontal cortex volume predicts brain reward circuitry activation in a taste reinforcement-learning paradigm that has been associated with dopamine function.Results:Obese individuals displayed lower gray and associated white matter volumes (P<0.05 family-wise error (FWE)- small volume corrected) compared with controls in the orbitofrontal cortex, striatum and insula. White matter integrity was reduced in obese individuals in fiber tracts including the external capsule, corona radiata, sagittal stratum, and the uncinate, inferior fronto-occipital, and inferior longitudinal fasciculi. Gray matter volume of the gyrus rectus at the medial edge of the orbitofrontal cortex predicted functional taste reward-learning response in frontal cortex, insula, basal ganglia, amygdala, hypothalamus and anterior cingulate cortex in control but not obese individuals.Conclusions:This study indicates a strong association between medial orbitofrontal cortex volume and taste reinforcement-learning activation in the brain in control but not in obese women. Lower brain volumes in the orbitofrontal cortex and other brain regions associated with taste reward function as well as lower integrity of connecting pathways in obesity (OB) may support a more widespread disruption of reward pathways. The medial orbitofrontal cortex is an important structure in the termination of food intake and disturbances in this and related structures could contribute to overconsumption of food in obesity.