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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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Conflict Disclosures In Nutrition Research

As someone who has often engaged in research projects, consultation, or speaking engagements sponsored or otherwise supported by industry (all of which I happily acknowledge and declare), I am a keen observer of the ongoing discussion about when and how researchers need to be wary of potential biases and conflicts. As I pointed out in previous posts, among all of the potential conflicts, the financial one is perhaps the easiest to declare and otherwise manage. A recent article by John Ionnadis and John Trepanowski, published in JAMA, discusses the wide range of conflicts (most of which may be non-financial), that one may wish to have declared and exposed, especially when it comes to nutrition research. The authors single our nutrition research for good reasons: “…the totality of an individual’s diet has important effects on health, most nutrients and foods individually have ambiguously tiny (or nonexistent) effects. Substantial reliance on observational data for which causal inference is notoriously difficult also limits the clarifying ability of nutrition science. When the data are not clear, opinions and conflicts of interest both financial and nonfinancial may influence research articles, editorials, guidelines, and laws. Therefore, disclosure policies are an important safeguard to help identify potential bias. “ While the potential for financial conflict in relationship to the food industry is well recognised and there are now well-established “disclosure norms”, other conflicts, of which there are many, are not routinely acknowledged, let alone, disclosed. For one, there are significant financial conflicts that have nothing to do with taking money from industry: “Many nutrition scientists and experts write books about their opinions and diet preferences. Given the interest of the public in this topic, books about nutrition, diets, and weight loss often appear on best-selling lists, even though most offer little to no evidence to support their frequently bold claims.” Furthermore, “Financial conflicts of interest can also appear in unexpected places. For example, many not-for-profit nutrition initiatives require considerable donor money to stay solvent. Public visibility through the scientific literature and its reverberation through press releases, other media coverage, and social media magnification can be critical in this regard.” Even these financial conflicts can perhaps be dealt with through established disclosure norms. But conflicts can get even more complicated when it starts reflecting researchers’ own personal views and biases:: “Allegiance bias and preference for favorite theories are prevalent across science and can affect any field of study. It is… 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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Better Fat Than Unfit

The 2018 JAMA special issue on obesity also includes a brief paper by Ann Blair Kennedy and colleagues reviewing the debate (which really isn’t much of a debate to anyone who knows the data) on whether it is more important to be fit than to worry about being fat (it is). As the authors review, there is now ample data showing that cardio-respiratory fitness (CRF) is far more important for the prediction of cardiovascular mortality than the level of fatness (measured as BMI or otherwise). In fact, once you account for differences in “fitness”, actual BMI levels almost cease to matter in terms of predicting longevity. Unfortunately, as the authors point out, most studies linking obesity to cardiovascular outcomes (including studies on the so-called obesity “paradox”), fail to properly measure or account for cardiovascular fitness, thereby ignoring the most important confounder of this relationship. For clinicians (and anyone concerned about their excess weight), it is helpful to remember that while achieving and maintaining a significant weight loss is a difficult (and often futile) undertaking, achieving and maintaining a reasonable degree of cardiorespiratory fitness is possible at virtually any shape or size. Thus, as the authors point out, “…in current US society, many people progressively gain weight and lose CRF as they age. Conceivably, maintaining CRF may be more important than preventing the development of obesity. However, for people who are overweight or have mild to moderate obesity, there are effective ways to improve CRF, including exercise and lifestyle interventions and there is general agreement that having low levels of PA is unhealthy. Increasing PA to help keep individuals from becoming unfit can be achieved if patients meet current PA guidelines of 150 minutes of moderate or 75 minutes of vigorous PA per week.” Clearly, if your primary concern related to your patients’ excess body fat is about their cardiovascular health, you would probably be doing them a far greater service by getting them to improve their cardiorespiratory fitness rather than simply lose a few pounds (and no, exercise is not the best way to lose weight!). On the other hand, if there are other health issues that are of primary concern (e.g. sleep apnea, osteoarthritis, fatty liver disease, etc.) or the degree of excess fat significantly affects mobility or other aspects of quality of life, then perhaps a frank discussion about available and effective “weight-loss” treatments appears warranted. Let us not… Read More »

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