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 »
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 »
In my talks, I have often joked about how to best keep weight off – just carry around a backpack that contains the lost pounds to fool the body into thinking the weight is still there. It turns out that what was intended as a joke, may in fact not be all too far from how the body actually regulates body weight. As readers of these posts are well aware, body weight is tightly controlled by a complex neuroendocrine feedback system that effectively defends the body against weight loss (and somewhat, albeit less efficiently, protects against excessive weight gain). Countless animal experiments (and human observations) show that following weight loss, more often than not, body weight is regained, generally precisely to the level of initial weight. With the discovery of leptin in the early 90s, an important afferent part of this feedback system became clear. Loss of fat mass leads to a substantial decrease in leptin levels, which in turn results in increased appetite and decreased metabolic rate, both favouring weight regain and thus, restoration of body weight to initial levels. Now, an international team of researchers led by John-Olov Jansson from the University of Gothenburg, Sweden, in a paper published in the Proceeding of the National Academy of Science (PNAS), provides compelling evidence for the existence of another afferent signal involved in body weight regulation – one derived from weight-bearing bones. Prompted by observations that prolonged sedentariness can promote weight gain, independent of physical activity, the researchers hypothesised that, “…there is a homeostat in the lower extremities regulating body weight with an impact on fat mass. Such a homeostat would (together with leptin) ensure sufficient whole body energy depots but still protect land-living animals from becoming too heavy. A prerequisite for such homeostatic regulation of body weight is that the integration center, which may be in the brain, receives afferent information from a body weight sensor. Thereafter, the integration center may adjust the body weight by acting on an effector.” In a first series of experiments, the researchers observed that implanting a weight corresponding to about 15% of body weight into rodents (rats and mice), resulted in a rapid “spontaneous” adjustment in body weight so that the combined weight of the animal plus the weight implant corresponded more-or-less to that of control animals. Within two weeks of implanting the weights, ∼80% of the increased loading was counteracted by reduced… Read More »
There is no reasonable argument against the fact that excess weight gain is one of the key drivers of diabetes risk, and it should come as no surprise to anyone, that losing weight (though bariatric surgery or otherwise) dramatically improves glycemic control in people living with type 2 diabetes. So what exactly can we learn from the DIRECT study published by Michael Lean and colleagues in The Lancet? For one, this is a large cluster-randomised trial of obesity intervention conducted entirely in a non-specialist primary care setting with significant weight loss (at least 15 Kg) and diabetes remission (defined as glycated haemoglobin (HbA1c) of less than 6·5% after at least 2 months off all antidiabetic medications) as the pre-defined primary outcome at 12 months. In the intervention centres, a nurse or dietitian (as available locally) was given a total of 8 h structured training by the study research dietitians experienced in the Counterweight-Plus program. Initial weight loss was induced with a total diet replacement phase using a low energy formula diet (825–853 kcal/day) for 3 months (extendable up to 5 months if wished by participant), followed by structured food reintroduction of 2–8 weeks (about 50% carbohydrate, 35% total fat, and 15% protein), and an ongoing structured programme with monthly visits for long-term weight loss maintenance. Given the primary care non-specialist setting of this trial, the key findings (as summarized by the authors), were perhaps surprising: “Just less than a quarter of participants in the intervention group achieved weight loss of 15 kg or more at 12 months, half maintained more than 10 kg loss, and almost half had remission of diabetes, off antidiabetic medication….Remission was closely related to the degree of weight loss maintained at 12 months, with achievement in 86% of participants with at least 15 kg weight loss, and 73% of those with weight loss of 10 kg or more. 28% of all eligible individuals volunteered to participate,17 and 79% completed the intensive total diet replacement phase…” In general, the intervention was well tolerated with 117 out of 150 participants (78%) in the intervention group completing the intervention. So here are the key learning from DIRECT: For one, there should no longer be any doubt that “remission” of Type 2 diabetes is possible in a substantial number of patients, if we can help them achieve and sustain significant weight loss – the odds of experiencing remission are directly proportional… Read More »
Readers will recall, that once-weekly injections of the novel long-acting GLP-1 analogue semaglutide was recently shown (in patients with type 2 diabetes) to result in a rather impressive weight loss. Now, a phase II dose-finding study comparing various oral doses of semaglutide to subcutaneous injections in patients with type 2 diabetes was just published in JAMA. The 26-week trial with 5-week follow-up included around 600 patients with type 2 diabetes and insufficient glycemic control using diet and exercise alone or a stable dose of metformin were randomized to once-daily oral semaglutide of 2.5 mg (n = 70), 5 mg (n = 70), 10 mg (n = 70), 20 mg (n = 70), 40-mg 4-week dose escalation (standard escalation; n = 71), 40-mg 8-week dose escalation (slow escalation; n = 70), 40-mg 2-week dose escalation (fast escalation, n = 70), oral placebo (n = 71; double-blind) or once-weekly subcutaneous semaglutide of 1.0 mg (n = 70) for 26 weeks. Mean change in HbA1c level from baseline to week 26 decreased with oral semaglutide (dosage-dependent range, −0.7% to −1.9%) and subcutaneous semaglutide (−1.9%) and placebo (−0.3%); Significant reductions were also seen in body weight with both oral (dosage-dependent range, −2.1 kg to −6.9 kg) and subcutaneous semaglutide (−6.4 kg) vs placebo (−1.2 kg)> Adverse events (largely consisting of mild to moderate gastrointestinal events) were as expected and relatively comparable between the treatment arms. Although this was a diabetes study, these findings clearly hold promise for the further development of an oral formulation of semaglutide for the obesity indication. @DrSharma Tønsberg, Noway Disclaimer: I have served as a consultant for Novo Nordisk, the maker of semaglutide.