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Can Planned Cheating Help You Stick With Your Diet?

pepperoni-pizza-slice-3Many diet plans praise the importance of strict adherence to whatever the storyline of the diet happens to be. This includes tips on what foods to avoid or to never eat. Indulging in these “forbidden” foods, is considered cheating and failure.

Now, research by┬áRita Coelho do Vale and colleagues, published in the Journal of Consumer Psychology, explores the notion that planned “cheats” can substantially improve adherence with restrictive diets.

Using a set of controlled dietary experiments (both simulated and real dieting), the researchers tested the notion that┬ágoal deviations (a more scientific term for “cheats”) in the plan helps consumers to regain or even improve self-regulatory resources along the goal-pursuit process and can thus enhance the likelihood that the final goal is attained.

That, is exactly what they found:

Compared to individuals who followed a straight and rigid goal, individuals with planned deviations helped subjects┬áregain self-regulatory resources, helped┬ámaintain subjects’ motivation to pursue with regulatory tasks, and (3) has a positive impact on affect experienced, which are all likely to facilitate long-term goal-adherence.

Thus, the authors conclude that, “…it may be beneficial for long-term goal-success to occasionally be bad, as long it is planned.

This is not really that new to those of us, who recommend or use planned “treats” as a way to make otherwise restrictive diets bearable.

Good to see that there is now some research to support this notion.

@DrSharma
Edmonton, AB

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What Behaviours Are Important For Optimal Outcomes With Bariatric Surgery?

sharma-obesity-gastric_bypass_roux-en-y3Bariatric surgery is by far the most effective treatment for severe obesity but outcomes vary from one patient to the next.

Now a paper by James Mitchell and colleagues, published in JAMA Surgery, reports on the postoperative eating behaviors and weight control strategies that are associated with differences in body weight seen at 3 years after bariatric surgery.

The study looks at self-reported data from over 2000 participants in the The Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study, a multicenter observational cohort study at 10 US hospitals in 6 geographically diverse clinical centers in the USA. Participants completed detailed surveys regarding eating and weight control behaviors prior to surgery and then annually after surgery for 3 years.

The researchers assessed 25 postoperative behaviors related to eating, weight control practices, and the use of alcohol, smoking, and illegal drugs.

The three key behaviours associated with poor outcomes were lack of weekly self-weighing, continuing to eat when feeling full more than once a week, and eating continuously during the day.

Thus, a participant who postoperatively started to self-weigh regularly, stopped eating when feeling full, and stopped eating continuously during the day after surgery would be predicted to lose almost 40% of their baseline weight compared to only 24% weight loss in participants who did not adopt these behaviours.

Other behaviours that had negative influences on outcomes included problematic use of alcohol, smoking and illegal drugs.

Thus, as one may have suspected all along, helping patients adopt and adhere to behavioural changes that include self-montioring and mindful eating behaviours can be expected to substantially affect the success of bariatric surgery.

@DrSharmma
Seoul, South Korea

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Zafgen Abandons Belanorib Program But Continues Exploring MetAP2 Inhibitor For Obesity

sharma-obesity-insulin-injectionRegular readers may recall previous posts on the novel anti-obesity compound belanorib, a MetAP2 inhibitor that showed remarkable weight loss efficacy both in patients with Prader-Willi Syndrome as well as hypothalamic obesity.

Unfortunately, as noted before, several cases of venous thromoboembolisms led to a halt of ongoing trials during which the company (Zafgen) sought to better understand the possible mechanism for this serious adverse effect and explore the possibility of implementing a risk mitigation strategy.

As announced by the company in a press release earlier this week,

“Following its discussions with the FDA and review of other considerations, Zafgen has determined that the obstacles, costs and development timelines to obtain marketing approval for beloranib are too great to justify additional investment in the program, particularly given the promising emerging profile of ZGN-1061. The Company is therefore suspending further development of beloranib in order to focus its resources on ZGN-1061.”

The press release also describes the new compound ZGN-1061 as a,

“…fumagillin-class, injectable small molecule second generation MetAP2 inhibitor that was discovered by Zafgen’s researchers and has been shown to have an improved profile relative to previous inhibitors in the class.┬áLike other MetAP2 inhibitors that have shown promise in the treatment of metabolic diseases including severe and complicated obesity, ZGN-1061 modulates the activity of key cellular processes that control the body’s ability to make and store fat, and utilize fat and glucose as an energy source.┬áZGN-1061 is also anticipated to help reduce hunger and restore balance to fat metabolism, enabling calories to once again be used as a productive energy source, leading to weight loss and improved metabolic control. ZGN-1061 has an emerging safety profile and dosage form that are believed to be appropriate for the treatment of prevalent forms of severe and complicated obesity, and is currently in Phase 1 clinical development. Zafgen holds exclusive worldwide rights for the development and commercialization of ZGN-1061.”

According to the press release,

“The compound has similar efficacy, potency, and range of activity in animal models of obesity as beloranib, but displays highly differentiated properties and a reduced potential to impact thrombosis, supporting the value of the compound as a more highly optimized MetAP2 inhibitor.”

Screening of patients for a Phase 1 clinical trial evaluating ZGN-1061 for safety, tolerability, and weight loss efficacy over four weeks of treatment is currently underway.

@DrSharma
Edmonton, AB

Disclaimer: I have served as a consultant to Zafgen.

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POMC Mutation Obesity Responds To Melanocortin-4 Receptor Agonist

sharma-obesity-hypothalamusMelanocyte-stimulating hormone (a-MSH), which is produced from the hormone precursor proopiomelanocortin (POMC) and acts on the hypothalamic melanocortin-4 receptor, plays a key role in the regulation of satiety and energy expenditure.

In very rare instances, mutations of the gene coding for POMC can cause severe early onset obesity characterised by increased appetite. Due to other effects of POMC deficiency, patients will present with pale skin, red hair and clinical signs of hypocortisolism.

Now, a paper by Peter K├╝hnen and colleagues published in the New England Journal of Medicine, shows that treating patients with the melanocortin-4 receptor agonist, setmelanotide, can result in significant reduction in appetite and body weight.

The open-label study was performed in two adult patients with POMC deficiency, in cooperation with Rhythm Pharmaceuticals, which provided the study medication and regulatory support.

Both patients weighed around 150 Kg with marked hyperphagia and both responded to treatment with a substantial reduction in appetite and dramatic weight loss of over 20 Kg over 12-13 weeks.

After a brief interruption, one patient was again treated for 42 weeks, ultimately losing 51 kg (32.9% of her initial body weight).

As the authors note,

“Setmelanotide appeared to completely reverse hyperphagia, leading to impressive weight loss and normalization of insulin resistance. More important, both patients reported a dramatic improvement in their quality of life after the initiation of setmelanotide therapy. Moreover, the substantial and ongoing reduction in body weight was similar to the changes observed after leptin administration in patients with leptin deficiency.”

Over all the treatment was well tolerated with no major adverse effects.

While these observations were made in very rare patients with documented POMC deficiency, these findings may have broader implications for individuals with more common “garden-variety” obesity.

“Both patients described here had very high leptin levels before treatment, suggesting leptin resistance. In patients with proopiomelanocortin deficiency, the leptin signal is probably not properly transduced into anorexigenic responses, given the lack of melanocyte-stimulating hormone. Setmelanotide substitutes for melanocyte-stimulating hormone and binds at its receptor, thus overcoming leptin resistance. On the basis of the observation that obese patients without known genetic abnormalities have severe leptin resistance and regain weight owing to a post-dieting increase in appetite, we speculate that setmelanotide may also be effective in nongenetic forms of obesity.”

Appropriate studies in patients with non-POMC deficient obesity are currently underway.

@DrSharma
Atlanta, GA

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Does Glycemic Response to Food Really Affect Appetite?

GI-Foods-7-HealthA popular narrative by proponents of low-glycemic index foods is the notion that high-glycemic index foods lead to a surge in plasma glucose, which in turn stimulates a spike in insulin levels, resulting in a rapid drop in blood glucose levels and an increase in appetite (“crash and crave”).

While this narrative is both biologically plausible and has been popularised by countless low-GI diets and products, the actual science of whether this story really holds true is less robust that you may think.

Now, a study by Bernd Schultes and colleagues, published in Appetite, seriously challenges this narrative.

The study was specifically designed to test the hypothesis that inducing glycemic fluctuations by intravenous glucose infusion is associated with concurrent changes in hunger, appetite, and satiety.

Using a single blind, counter-balanced crossover study in 15 healthy young men, participants were either given an i.v. infusion of 500 ml of a solution containing 50 g glucose or 0.9% saline, respectively, over a 1-h period.

On each occasion, the infusions were performed one hour after a light breakfast (284 kcal).

I.v. glucose markedly increased glucose and insulin concentrations (peak glucose level: 9.7 vs. 5.3 mmol/l in the control group); peak insulin level: 370 vs. 109) followed by a sharp decline in glycaemia to a nadir of 3.0 in the glucose study vs. 3.9 mmol/l at the corresponding time in the control condition.

Despite this wide glycemic fluctuation in the glucose infusion condition, the subjective feelings of hunger, appetite satiety, and fullness did not differ from the control condition throughout the experiment.

Clearly, these findings speak against the conventional narrative that fluctuations in glycemia and insulinemia represent major signals in the short-term regulation of hunger and satiety.

Or, as the authors put it,

Our findings might also challenge the popular concept of low glycemic index diets to lose body weight. Advocates of this dietary approach often argue that large glycemic (and concurrent insulinemic) fluctuations induced by the intake of high glycemic index foods can trigger feelings of hunger and, thus, on the long run favor weight gain. Our results argue against this notion since the sharp drop in circulating glucose after the end of the glucose infusion remained without effect on hunger ratings, at least within the time period covered by our experiment.

As they further note, these findings may explain why,

“…several clinical dietary intervention trials have failed to show an advantage of low glycemic index dietary approaches for weight loss in overweight/obese subjects in comparison with other dietary approaches.”

The lesson here, I guess is that, just because there is a seemingly compelling narrative to support an idea, it does not mean that that’s how biology in real life actually works.

@DrSharma
Edmonton, AB

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