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blog – Dr. Sharma's Obesity Notes



Views and news on obesity research and management from the University of Alberta Obesity Chair



Last Build Date: Mon, 16 Apr 2018 12:00:09 +0000

 



When To Recommend Weight Loss For Obesity

Mon, 16 Apr 2018 12:00:09 +0000

Obesity medicine, which I define as the medical care of someone living with obesity, should approach patients holistically with the aim of improving their overall health and well-being. Advice to lose weight may or may not be part of obesity management – much can be gained for someone living with obesity by promoting their health behaviours, getting them to feel better about themselves, improving their mental health, and helping them better managing their health issues.  Much of this can be achieved with no or very little weight loss. Thus, we must consider the question of when weight loss would specifically need to be part of the treatment objectives. In my own practice, I approach this problem by considering the following three questions: Is this a problem unrelated to abnormal or excess body weight? Is this a problem aggravated by abnormal or excess body weight? Is this a problem caused by abnormal or excess body weight? From what I hear from my patients, the most common mistakes in medical practice fall into the first group – trying to address unrelated issues with weight loss recommendations. There are endless stories of patients going to see their health provider with problems clearly unrelated to their body fat (e.g. a broken arm, a sore throat, the flu, depression, migraines, etc.), who simply get told to lose weight. Indeed, there is evidence to suggest that patients with obesity are less likely to undergo diagnostic testing, most likely based on the assumption that their problems are simply related to their excess weight. This is not only where grave medical errors can be made (late or misdiagnosis), but also where the advice to lose weight is clearly wrong. If the presenting problem has nothing to do with excess weight, then no amount of weight loss will fix it. The second category deals with issues that are not causally related to abnormal or excess body fat but where the underlying problem either causes more symptoms or is more difficult to treat because of the patient’s size or fat distribution. There are countless medical problems that fall into this category. For e.g.  a heart or respiratory problem entirely unrelated to excess weight (e.g. a valvular defect or asthma) can become worse, cause more symptoms, or be much more difficult to treat simply because of the patient’s size. This group also includes issues like neck or joint pain from a trauma… Read More »



The Heterogeneity of Obesity

Tue, 27 Mar 2018 12:00:32 +0000

In the same manner in that there is not one predisposing factor for the development of obesity, the phenotypic clinical presentation of obesity is likewise extraordinarily heterogenous. (This has some authors speaking of “obesities” rather than “obesity”). While it is now well established that BMI is a measure of size rather than health, it is perhaps less well recognised how the different types of body fat and their storage in various fat depots and organs can contribute to cardiometabolic disease (location, location, location!). Now, a comprehensive review by Ian Neeland from the University of Texas Southwestern Medical Center, Dallas, together with my colleagues Paul Poirier and JP Despres from Laval University in Quebec, published in Circulation discusses the cardiovascular and metabolic heterogeneity of obesity. As the authors point out, “Although the BMI has been a convenient and simple index to monitor the growth in obesity prevalence at the population level, many metabolic and clinical studies have revealed that obesity, when defined on the basis of the BMI alone, is a remarkably heterogeneous condition. For instance, patients with similar body weight or BMI values have been shown to display markedly different comorbidities and levels of health risk.” Not only has BMI never emerged as a significant component in risk engines such as the Framingham risk score, there are many individuals with obesity who never develop metabolic complications or heart disease during the course of their life. The paper offers a good review of what the author describe as adipose dysfunction or “adiposopathy” = “sick fat”. Thus, in some individuals, there is an accumulation of “unhealthy” fat (particularly visceral and ectopic fat), whereas in others, excess fat predominantly consists of “healthy” fat (predominantly in subcutaneous depots such as the hips and thighs). The authors thus emphasise the importance of measuring fat location with methods ranging from simple anthropometric measures (e.g. waist circumference) to comprehensive imaging techniques (e.g. MRI). The authors also provide a succinct overview of exactly how this “sick fat” contributes to cardiometabolic risk and briefly touches on the behavioural, medical, and surgical management of patients with obesity and elevated cardiometabolic risk. I, for one, was also happy to see the inclusion of the Edmonton Obesity Staging System in their reflections on this complex issue. This paper is certainly suggested reading for anyone interested in the link between obesity and cardiovascular disease. @DrSharma Edmonton, AB



The Three Clinical Faces of Obesity

Wed, 07 Mar 2018 13:00:55 +0000

In my experience, patients presenting with obesity tend to fall into three categories, each of which requires a distinct management approach. They are 1) Active Gainers, 2) Weight Stable, and 3) Post-Weight Loss. Active Gainers are patients currently at their lifetime maximum and continuing to gain significant amounts of weight – i.e. more than the usual 0.5 to 1 lb/year. Patients in this category require immediate attention – if nothing happens, their weight will most likely just continue to increase. The good news is that in almost every patient in this category, there is an identifiable reason for the ongoing weight gain – this can be psychosocial (e.g. depression, binge-eating disorder, etc.), due to a medical comorbidity (arthritis, chronic pain, etc.) or medications (e.g. atypical antipsychotics, hypoglycemic agents, etc.). From a management perspective, the sooner we identify and address the underlying problem, the sooner we can slow or even halt the rate of weight gain – in this patient – gaining less weight than before is the first sign of success. There is really no point trying to embark on losing weight as long as the underlying problem driving the weight gain has not been addressed, as this is likely to make sustained weight loss even more unlikely that it already is.. Weight Stable patients are those that present with excess weight but are relatively weight stable. Even though they may be at their lifetime maximum, they have been pretty much the same weight (perhaps a few lbs up or down but nothing drastic) for several years (sometimes even decades). By definition, a patient who is weight stable is in caloric balance, and thus, by definition is not eating too much. In fact, these patients are eating the exact number of calories needed to sustain their bodies, which is why they are weight stable. (Remember, even if you are weight-stable eating 4000 Cal a day, you are technically not “overeating”.)  These patients of course have experienced significant weight gain in the past (historical weight gain), but whatever it was that caused them to gain weight is no longer an active problem (e.g. pregnancy, past depression, etc) – and therefore, probably doesn’t need to addressed (although, I always find it of interest to find out what caused the weight gain in the first place). With these patients, we can determine whether or not their weight is affecting their health, and if… Read More »



Long-Term Mental Health Impact of Childhood Bullying

Fri, 23 Feb 2018 13:00:05 +0000

As I hear regularly from my patients, virtually all of them, who were larger during childhood have experienced weight-based bullying – sadly, weight-based bullying remains among the top causes of bullying among kids today. Now, a paper by Marie-Claude Geoffroy and coleagues, in a paper published in CMAJ, provide data on a longitudinal assessment of the impact of childhood bullying (peer victimisation) on mental health outcomes in midadolescense. The researchers examined data from the Quebec Longitudinal Study of Child Development, a prospective cohort of children born in 1997/98 who were followed until age 15 years. Data was available for 1363 participants with self-reported victimization from ages 6 to 13 years and their mental health status at 15 years. Overall, there were three 3 trajectories of peer victimization – most kids fell into the groups with little (27%) or moderate (60%). However, about 15% of kids fell into a third group, who apparently had been chronically exposed to the most severe and long-lasting levels of victimization. While there seemed to be little (if any) mental health impact in the mild and moderate group, kids in the severely bullied group were 2.6 times likelier to experience debilitating depression, 3.3. times more likely to experience generalised anxiety, and 3.5 times more likely to be suicidal, than individuals in mildly victimized individuals. Thus, as the authors conclude, “Childhood peer victimization begins at a young age and can lead to mental illness in adolescence. Interventions to prevent severe peer victimisation should begin before children start school.” While the paper does not specifically single out the motives for bullying, given the prevalence of weight/size-based bullying, these findings are probably quite relevant for those of us involved in pediatric obesity management. @DrSharma Edmonton, AB



Sleep Restriction Leads To Less Fat-Loss

Wed, 21 Feb 2018 13:00:49 +0000

Regular readers will be well aware of the increasing data supporting the importance of adequate restorative sleep on metabolism and weight management. Now, a study by Wang Xuewen and colleagues, published in SLEEP, shows just how detrimental sleep deprivation can be during a weight-loss diet. Their study included thirty-six 35-55 years oldadults with overweight or obesity, who were randomized to an 8-week caloric restriction (CR) regimen alone (n=15) or combined with sleep restriction (CR+SR) (n=21). All participants were instructed to restrict daily calorie intake to 95% of their measured resting metabolic rate. Participants in the CR+SR group were also instructed to reduce time in bed on 5 nights and to sleep ad libitum on the other 2 nights each week. The CR+SR group reduced sleep by about 60 minutes per day during sleep restriction days, and increased sleep by 60 minutes per day during ad libitum sleep days, resulting in a sleep reduction of about 170 minutes per week.Although both groups lost a similar amount of weight during the study ~3 Kg). However, the proportion of total mass lost as fat was significantly greater  in the CR group (80% vs. 16%). In line with this substantial difference in fat reduction, resting respiratory quotient was significantly reduced only in the CR group. Importantly, these effects of sleep deprivation on fat loss were observed despite the fact that subjects were allowed to sleep as much as they wanted on the non-restricted days. This suggests that the negative effects of sleep deprivation during weight loss are not made up by “make-up” sleep. Although overall, the amount of weight lost in this study is modest, it clearly fits with the notion that adequate sleep (in this case, during weight loss), can be an important part of weight management. Clearly, the role of sleep in energy homeostasis will remain an interesting field of research, as we continue learning more about how sleep (or rather lack of it) affects metabolism. @DrSharma Edmonton, AB



Fit-Fat Paradox Holds For People With Severe Obesity

Thu, 15 Feb 2018 13:00:12 +0000

Regular readers will be quite familiar with the findings that cardiometabolic health appears to be far more related to “fitness” than to “fatness” – in other words, it is quite possible to mitigate the metabolic risks commonly associated with excess body fat by improving cardiorespiratory fitness. Now, a study by Kathy Do and colleagues from York University, Toronto, published in BMC Obesity, shows that this relationship also holds for people with quite severe obesity. The researcher studied 853 patients from the Wharton Medical Clinics in the Greater Toronto Area, who  completed a clinical examination and maximal treadmill test. Patients were then categorized into fit and unfit based on age- and sex-categories and in terms of fatness based on BMI class. Within the sample, 41% of participants with mild obesity (BMI<35) had high fitness whereas only 25% and 11% of the participants with moderate (BMI 35-40) and severe obesity (BMI>40), respectively, had high fitness. Individuals with higher fitness tended to be younger and more likely to be female. While overall fitness did not appear to be independently associated with most of the metabolic risk factors (except systolic blood pressure and triglycerides), the effect of fitness in patients with severe obesity was more pronounced. Thus, the prevalent relative risk for pre-clinical hypertension, hypertriglyceridemia and hypoalphalipoproteinemia and pre-diabetes was only elevated in the unfit moderate and severe obesity groups, and fitness groups were only significantly different in their relative risk for prevalent pre-clinical hypertension within the severe obesity group. Similarly, high fitness was associated with smaller waist circumferences, with differences between high and low fitness being larger in those with severe obesity than with mild obesity. Based on these findings, the researchers conclude that the favourable associations of having high fitness on health may be similar if not augmented in individuals with severe compared to mild obesity. However, it is also apparent based on the rather low number of “fit” individuals in the severe obesity category (only about 1 in 10), that maintaining a high level of fitness proves to be more challenging the higher the BMI. @DrSharma Edmonton, AB



Can Liraglutide Help Grow New Fat Cells?

Wed, 14 Feb 2018 13:00:22 +0000

The human GLP-1 analogue liraglutide is now approved for the long-term medical treatment of obesity in an ever-increasing number of countries. Its safety and clinical effectiveness is now well established and there is no doubt that this is an important addition to the rather limited number of treatment options available to people living with obesity. Interestingly, however, liraglutide has also been shown to promote the differentiation of pre-adipocytes or, in other words, promote the formation of new fat cells. While this may seen worrying or even counter-intuitive, we much remember that having more (smaller) rather than fewer (bigger) fat cells actually has substantial metabolic advantage s- there is indeed ample data showing that large adipocyte cell size and limited capacity to grow fat cells (the extreme case of which is seen in people with lipodystrophy) is actually a key risk factor for metabolic problems including insulin resistance, possible by promoting the accumulation of ectopic fat (e.g. in liver and skeletal muscle). Now, a paper by Yongmei Liand colleagues, published in Molecular Medicine Reports provides additional insight into the cellular pathways involved in liraglutide’s adipogenic effects. Using a series of in vitro experiments, the researchers show that liraglutide does indeed promote the adipogenic differentiation of 3T3-L1 cells (a widely used murine preadipocyte cell line)  through a process that upregulates the expression of C/EBPα and PPARγ at the early phase of adipogenic differentiation, promots the expression of lipogenesis associated genes including aP2, and enhances the accumulated of lipids. At the same time, liraglutide appears to suppress cell proliferation via the Hippo‑yes‑associated protein (YAP) signaling pathway, thereby allowing these cells to transform into mature adipocytes sooner. How relevant these observations are for humans remains to be seen, but certainly the promotion of adipogenic differentiation may hold the potential for improving insulin sensitivity and reducing the metabolic risks associated with excess weight gain. @DrSharma Edmonton, AB Disclaimer: I have received speaking and consulting honoraria from Novo Nordisk, the maker of liraglutide.  



Semaglutide Continues To Hold Promise For Obesity Treatment

Tue, 06 Feb 2018 13:00:56 +0000

This week, the Lancet published the results of the SUSTAIN7 trial, an open-label, parallel-group, phase 3b trial done at 194 hospitals, clinical institutions or private practices in 16 countries. Eligible patients with type 2 diabetes (HbA1c 7·0–10·5% on metformin monotherapy, n=1201), were randomised to once-weekly injections of the GLP-1 analogues semaglutide 0·5 mg, dulaglutide 0·75 mg, semaglutide 1·0 mg, or dulaglutide 1·5 mg. Over the 40 weeks of treatment, participants on semaglutide had a greater reduction in HbA1c than participants who were on corresponding doses of dulaglutide. More interesting, in the context of this blog, semaglutide was also almost twice as effective in lowering mean body weight than dulaglutide. Thus, bodyweight was reduced by 4·6 kg with semaglutide 0·5 mg compared with 2·3 kg with dulaglutide 0·75 mg and by 6·5 kg with semaglutide 1·0 mg compared with 3·0 kg with dulaglutide 1·5 mg. As expected, the most frequent adverse effects were gastrointestinal. Given that this was not actually a trial designed to maximise weight loss (as would have been attempted in a study primarily designed to study semaglutide as a treatment for obesity), these changes in body weight are certainly quite impressive. These findings no doubt hold promise for the further development of semaglutide as an anti-obesity medication. @DrSharma Edmonton, CA Disclaimer: I have received speaking and consulting honoraria from Novo Nordisk, the maker of semaglutide



New European Guidelines on Medical Management After Bariatric Surgery

Fri, 02 Feb 2018 13:00:10 +0000

The European Association for the Study of Obesity (EASO) had now released the new OMTF guidelines Practical Recommendations of the Obesity Management Task Force of the European Association for the Study of Obesity for Post-Bariatric Surgery Medical Management. The guidelines provide the latest guidance on nutritional management, micronutrient supplementation, managing co-morbidities, pharmacotherapy, psychological management, and prevention and management of weight regain. The guidelines also address the issue of post-bariatric surgery pregnancy. Not covered are issues related to dealing with excess skin and rehabilitation (e.g. return to work, reintegration in social activities, education, etc.), both of significant importance, especially in people with severe obesity. As the authors note, “Bariatric surgery is in general safe and effective, but it can cause new clinical problems and it is associated with specific diagnostic, preventive and therapeutic needs. Special knowledge and skills of the clinicians are required in order to deliver appropriate and effective care to the post-bariatric patient. A post-bariatric multidisciplinary follow-up programme should be an integral part of the clinical pathway at centres delivering bariatric surgery, and it should be offered to patients requiring it” These guidelines are now available open access in Obesity Facts. @DrSharma Edmonton, AB



Reducing Cardiovascular Risk In Adolescents With Bariatric Surgery

Thu, 01 Feb 2018 13:00:13 +0000

Given the limited effectiveness of “lifestyle” interventions and the lack of access to medical treatments, many adolescents struggling with severe obesity are left with no option but to consider having bariatric surgery. Now, a paper by Marc Michalsky and colleagues on behalf of the Teens LABS Consortium, in a paper published in Pediatrics, describes the effect of bariatric surgery on cardiovascular risk factors in adolescents undergoing these procedures. The study includes 242 adolescents (76% girls, 72% white, mean age 17 ± 1.6 y,  median BMI 51) undergoing bariatric surgery (Roux-en-Y gastric bypass (n = 161), vertical sleeve gastrectomy (n = 67), or adjustable gastric banding (n = 14)), at five centers. At 3 years following surgery, weight was significantly lower in all groups (28%, 26%, and 8% for RYGB, VSG, and AGB, respectively). Hypertension, observed in 44% of participants, declined to 15% at 3 years. Dyslipidemia observed in 75% of participants, declining to 27% by 1 year and 29% by 3 years. This improvement was largely due to decrease in triclycerides and increases in HDL cholesterol. Baseline diabetes was present in 13% of participants with major metabolic improvement (0.5%) by 3 years. Similarly, baseline impaired fasting glucose (26%) and hyperinsulinemia (74%) dramatically improved by year 3 (4% and 20%, respectively). Improvements in these parameters were related to the degree of weight loss. Remission rates were negatively correlated to higher age and positively correlated to female sex and white race. Overall, the authors conclude that this study documents the improvements in cardiovascular risk factors in adolescent bariatric surgery. Unfortunately, the study does not present any information on surgical complications or reoperation rates, an obvious matter of concern when it comes to surgery in this young population. While there may well have been no alternative to surgical treatment in these kids, we can only hope that eventually medical treatments will become available for this population, hopefully with similar outcomes. Unfortunately, that may well still be a long way off. @DrSharma Edmonton, AB