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Reducing Cardiovascular Risk In Adolescents With Bariatric Surgery

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

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Molecular Changes During Weight Gain – Everyone Is Different

As one may well imagine, changes in body weight (up or down) can profoundly affect a vast number of hormonal and metabolic pathways. Now, a team of researchers led by Brian Piening and colleagues, in a paper published in Cell Systems used a broad “omics” based approach to study what happens when people lose ore gain weight. Specifically, the goal of this study was to: (1) assemble a comprehensive map of the molecular changes in humans (in circulating blood as well as the microbiome) that occur over the course of a carefully controlled weight gain and their reversibility with weight loss; and (2) determine whether inulin sensitive (IS) and insulin resistant (IR) individuals who are matched for degree of obesity demonstrate unique biomolecular signatures and/or pathway activation during similar weight gain. The study included 23 carefully selected healthy participants with BMI 25–35 kg/m2, were studied. Samples were collected at baseline. They then underwent a 30-day weight gain period (average 2.8 kg), followed by an eucaloric diet for 7 days, at which point a second fasted sample of blood and stool was collected. Each participant then underwent a caloric-restricted diet under nutritionist supervision for a subsequent 60-day period designed to return each participant back to his/her initial baseline weight, at which point a third set of fasted samples of blood and stool were collected. A subset of participants returned for a follow-up sampling approximately 3 months after the end of the perturbation.Insulin resistance was assessed at baseline using a modified insulin suppression test. The large-scale multi-omics assays performed at all time points on each participant included genomics, proteomics, metabolomics and microbiomics. Despite some differences between the IS and IR group (particularly in differential regulation of inflammatory/immune response pathways), overall, molecular changes were dominated by inter-personal variation (i.e. changes within the same individual), which accounted for more than 90% of the observed variance in some cases (e.g., cytokines). The most striking changes with weight gain were in inflammation response pathways (despite the rather modest weight gain) and were (fortunately) reversed by weight loss. As the authors note, “Comparing the variation in cytokine levels between multiple baselines in a single individual versus across individuals, we observed a striking difference: for almost all cytokines, the within-individual coefficient of variation was under 20%, whereas the variation across individuals was 40%–60%. This shows that our baseline cytokine profiles are unique to the individual, a point that has significant implications for one-size-fits-all clinical cytokine assays for the detection… Read More »

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How Precise Can Obesity Medicine Get?

Another article in the 2018 JAMA special issue on obesity is one by Susan and Jack Yanovski and deals with the issue of using a precision or “personalised” approach to obesity prevention and management. As we know, there are myriad factors that can lead to obesity (environmental, genetic, psychological, medical, etc., etc., etc.), with each patient having their own story and set of drivers and barriers. Furthermore, we know that for any given treatment (whether behavioural, medical, or surgical) there is wide variation in individual outcomes. So, being able to match the right treatment to the right patient, or even better, reliably predict a given patient’s response to a specific treatment could potentially improve outcomes and reduce patient burden and costs. However, as the authors note, currently the only real predictor to treatment response is how well patients respond during the early part of treatment. Thus, we know that patient who lose a significant amount of weight during the first few weeks of medical treatment, tend to have the best long-term success in terms of weight loss. However, this approach is also rather limited. In my own practice, I regularly see patients, who initially do well with behavioural, medical or surgical treatments, but eventually struggle, as well as patients who take longer to respond to a treatment before ultimately doing fine in the long term. We are of course a long way off from having any kind of genetic or other testing that would reliably predict patient responses to treatment. While this may become possible in the future, I am not holding my breath. Not only is every patient’s story different, but the many factors that can determine response (societal, behavioural, psychological, biological, etc.) are almost endless and, moreover, can even vary over time in a given individual. In fact, for most complex chronic diseases (e.g. diabetes, hypertension, depression, etc.), finding the best treatment for a given patient continues to be “trial and error”, or in other words, “empirical”. Despite all the progress in genetic research, this has not really changed for most other complex chronic diseases like hypertension, type 2 diabetes, or dyslipidemia (despite a few rare but notable exceptions). Moveover, as the authors point out, there are many other factors that will determine whether or not a given patient even has access to certain treatments, irrespective of whether or not that treatment is indeed the best treatment for… Read More »

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Counting Calories For Weight Loss – More of The Same

If there is one article in the 2018 special issue of JAMA on obesity that we could have well done without, it is surely the one by Eve Guth promoting the age-old notion that simply counting calories is a viable and effective means to manage body weight. As the author suggests: “It is better for physicians to advise patients to assess and then modify their current eating habits and then reduce their caloric ingestion by counting calories. Counseling patients to do this involves provision of simple handouts detailing the calorie content of common foods, suggested meal plan options, an explanation of a nutrition label, and a list of websites with more detailed information. Patients should be advised that eating about 3500 calories a week in excess of the amount of calories expended results in gaining 1 lb (0.45 kg) of body weight. If a patient reduces caloric ingestion by 500 calories per day for 7 days, she or he would lose about 1 lb of body weight per week, depending on a number of other factors. This is a reasonable and realistic place to start because this approach is easily understood and does not ask a patient to radically change behavior.” There is so much wrong with this approach, that it is hard to know exactly where to start. For one, this advise is based on the simplistic assumption that obesity is simply a matter of managing calories to achieve and sustain long-term weight loss. Not only, do we have ample evidence that these type of approaches rarely result in long-term sustained weight-loss but, more importantly this type of advice comfortably ignores the vast body of scientific literature that tells us that body weight is a tightly regulated physiological variable and that there are a host of complex neuroendocrine responses that will defend our bodies against long-term weight loss – mechanisms that most people (irrespective of whether they have obesity or not) will find it exceedingly hard to overcome with “will-power” alone. No doubt, caloric “awareness” can be an eye-opener for many patients and there is good evidence that keeping a food journal can positively influence dietary patterns and even reduce “emotional” eating. But the idea that cognitively harnessing “will-power” to count calories (a very “unnatural” behaviour indeed), thereby creating and sustaining a long-term state of caloric deficit is rather optimistic at best. In fact, legions of people who have been… Read More »

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Long-Term Health Outcomes After Bariatric Surgery

Another series of articles in the 2018 JAMA special issue on obesity, deals with the impact of bariatric surgery on health outcomes and overall mortality. The first article by Sayeed Ikramuddin and colleagues is an observational follow-up of a randomized clinical trial at 4 sites in the United States and Taiwan, involving 120 participants who had a hemoglobin A1c(HbA1c) level of 8.0% or higher and a BMI between 30.0 and 39.9. The study compared intensive lifestyle and medical management intervention based on the Diabetes Prevention Program and LookAHEAD trials for 2 years, with and without (60 participants each) Roux-en-Y gastric bypass surgery followed by observation to year 5. At 5 years, 13 participants (23%) in the gastric bypass group and 2 (4%) in the lifestyle-intensive medical management group had achieved the composite triple end point (HbA1c less than 7.0%, LDL cholesterol less than 100 mg/dL, and systolic blood pressure less than 130 mm Hg). In the fifth year, 31 patients (55%) in the gastric bypass group vs 8 (14%) in the lifestyle–medical management group achieved an HbA1c level of less than 7.0%. As is to be expected, surgical treatment resulted in more serious adverse events (66 vs 38 events), most frequently involving gastrointestinal and surgical complications such as strictures, small bowel obstructions, and leaks. A second study by Gunn Signe Jakobsen and colleagues from Norway, reports on changes in obesity related comorbidities in patients with severe obesity (BMI ≥40 or ≥35 and at least 1 comorbidity) undergoing bariatric surgery (n=932, 92 gastric bypass) or specialized medical (“lifestyle”) treatment (n=956) at a tertiary care outpatient center. Based on drugs dispensed according to the Norwegian Prescription Database and data from the Norwegian Patient Registry and a local laboratory database, surgically treated patients had a greater likelihood of remission (RR, 2.1) and lesser likelihood for new onset of hypertension (RR, 0.4), a greater likelihood of diabetes remission (RR, 3.9) but also a greater risk of new-onset depression (RR, 1.5) and treatment with opioids (RR, 1.3. Again, as expected, surgical patients had a greater risk for undergoing at least 1 additional gastrointestinal surgical procedure (RR, 2.0). From these findings the researchers conclude that adding gastric bypass to lifestyle and intensive medical management alone in patients with severe obesity and type 2 diabetes, there remained a significantly better composite triple end point in the surgical group at 5 years. The third study by Orna Reges and colleagues from… Read More »

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