Monday, December 15, 2014

Triple-Homone Breakthrough For Obesity?

The new peptide offers a triple hormone effect in a single-cell molecule. Credit: Indiana University

The new peptide offers a triple hormone effect in a single-cell molecule.
Credit: Indiana University

This week, a group of researchers working from Munich, Germany and Indiana, USA, report, what may be a major breakthrough in the treatment of obesity and type 2 diabetes.

In their paper, published in Nature Medicine, the researchers use a range of sophisticated experiments to demonstrate that a novel peptide, which combines agonistic actions of three hormones (GLP-1, GIP and glucagon) into a single molecule, can fully reverse diabetes and reduce body weight by over 30% in mice.

Despite this just being a mouse study, the triple combination findings are no accident. Rather, these researchers have rationally designed this molecule based on the known actions of these three hormones.

As the authors describe it, their finding

predominantly results from synergistic glucagon action to increase energy expenditure, GLP-1 action to reduce caloric intake and improve glucose control, and GIP action to potentiate the incretin effect and buffer against the diabetogenic effect of inherent glucagon activity.”

According to their report, this “designer” peptide,

“…demonstrates supraphysiological potency and equally aligned constituent activities at each receptor, all without cross-reactivity at other related receptors. Such balanced unimolecular triple agonism proved superior to any existing dual coagonists and best-in-class monoagonists to reduce body weight, enhance glycemic control and reverse hepatic steatosis in relevant rodent models.”

Similar activity in humans would indeed represent a breakthrough, potentially providing a medical treatment that may be as (if not more) potent than bariatric surgery.

While the path to human development is generally long and stony, there are at least some folks who are optimistic: the molecule has been licensed to  Marcadia Biotech Inc., now fully owned by the Swiss pharma giant Roche. 

Clearly, this will be an exciting space to watch.

@DrSharma
Edmonton, AB

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Friday, December 12, 2014

Prevalence and Treatment of Depression In Canada

sharma-obesity-mental-health1Depression can be a significant factor both in the development of obesity and as an important barrier to its treatment.

Now a paper by Sabrina Wong and colleagues from the University of British Columbia, in a paper published in CMAJ open, present data on the prevalence and treatment of depression in Canadian primary care practices.

The authors analysed electronic medical record data from the Canadian Primary Care Sentinel Surveillance Network, of over 300,000 patients who had at least one encounter with their primary care provider between Jan. 1, 2011, and Dec. 31, 2012.

Of these, 14% had a diagnosis of depression.

Women with a BMI greater than 30 were about 20% more likely to also have depression than women with a BMI below 25. No such relationship was noted in men.

Overall, 25% of individuals with a diagnosis of depression also had at least one other chronic condition as well as about 50% more doctor visits than individuals without depression.

Clearly, depression is a common problem in primary care and weight management in patients (particularly women) presenting with this problem needs to be addressed (not least because many of the medications often used to manage depression may well be part of the problem).

@DrSharma
Edmonton, AB

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Thursday, December 11, 2014

How Effective Is Obesity Management In Primary Care?

sharma-obesity-doctor-kidLosing weight with behavioural interventions in the context of a clinical trial, where you are often dealing with volunteers who are generally provided interventions that are far better structured and standardised than we can ever hope to deliver in a primary care settings, tells us little about the effectiveness of such interventions in real life.

Now a paper by Tom Wadden and colleagues from the University of Pennsylvania, published in JAMA, presents a systematic review of the behavioral treatment of obesity in patients encountered in primary care settings as delivered by primary care practitioners working alone or with trained interventionists (eg, medical assistants, registered dietitians), or by trained interventionists working independently..

A search of the literature yielded 12 trials, involving 3893 participants, that met inclusion-exclusion criteria and prespecified quality ratings.

At 6-months weight changes in the intervention groups ranged from a loss of 0.3 kg to 6.6 kg compared to a gain of 0.9 kg to a loss of 2.0 kg in the control group.

As one may expect, interventions that prescribed both reduced energy intake (eg, ≥ 500 kcal/d) and increased physical activity (eg, ≥150 minutes a week of walking), with traditional behavioral therapy, generally produced larger weight loss than interventions without all three specific components.

Also, more treatment sessions (in person or by telephone) were associated with greater mean weight loss and likelihood of patients losing 5% or more of baseline weight.

Unfortunately, overtime, weight loss in both groups declined with longer follow-up (12-24 months).

Thus, the authors conclude that,

“Intensive behavioral counseling can induce clinically meaningful weight loss, but there is little research on primary care practitioners providing such care. The present findings suggest that a range of trained interventionists, who deliver counseling in person or by telephone, could be considered for treating overweight or obesity in patients encountered in primary care settings.”

Whether any of this is worth the cost and effort was not discussed. My guess is that to see greater success in primary care we need better treatments that move well beyond the rather simplistic ‘eat-less move-more’ paradigm.

@DrSharma
Edmonton, AB

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Monday, December 8, 2014

Effectiveness Of Obesity Management For Osteoarthritis

sharma-obesity-knee-osteoarthritis1Osteoarthritis is one of the most common and disabling complications of obesity. Irrespective of whether or not the osteoarthritis is directly caused by excess weight, there is little doubt that the sheer mechanical forces acting on the affected joints will significantly impact mobility and quality of life.

Now the Canadian Agency for Drugs and Technologies in Health (CADTH) has released a report on the Clinical Effectiveness of Obesity Management Interventions Delivered in Primary Care for Patients with Osteoarthritis.

This systematic review of the literature leads to the following findings:

1) Dietary weight loss interventions, either alone or in combination with exercise produce greater reductions in the peak knee compressive force and plasma levels of interleukin-6 (IL-6) in knee OA patients compared with exercise-induced weight loss.

2) There is a significantly greater reduction in pain and improvements in functions in patients who received diet plus exercise interventions compared with either diet–only or exercise–only interventions.

3) Regardless of the type of weight-loss interventions, participants who lost 10% or more of baseline body weight had greater reductions in knee compressive force, systemic IL-6 concentrations, and pain, as well as gained greater improvement in function than those who lost less of their baseline weight.

4) Participants who lost the most weight also experienced greater loss of bone mass density at the femoral neck and hip, but not the spine, without a significant change of their baseline clinical classification with regards to osteoporosis or osteopenia.

Thus, in summary, weight loss, particularly when achieved through a combination of both diet and exercise can result in significant improvement in physical function, mobility, and pain scores in individuals with osteoarthritis.

Unfortunately, this is by no means easy to achieve and even harder to sustain.

Although I may sound like a broken record – we desperately need better treatments for obesity.

@DrSharma
Edmonton, AB

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Friday, November 28, 2014

When Something is Not Better Than Nothing

diet journalThis is the title of a recent article by Nikhil Dhurandar and other members of the Energy Balance Measurement Working Group (of which I am a member), published in the International Journal of Obesity and refers to the inadequacies of our current methods for assessing energy intake and expenditure.

In the paper, the authors argue that while an assessment of energy balance may well be a critical issue both for research and clinical practice, our current methods for assessing this are woefully inaccurate and may well be leading us in the wrong direction.

Thus, for example, there is no shortage of information on the fact that self-reported dietary energy intake (EI) is woefully inaccurate (despite all efforts over the past decades to try and make this more accurate) to the point of being near useless in individuals and even less meaningful in population studies – at least when it comes to the assessment of energy balance.

The same is unfortunately true for assessments of physical activity energy expenditure (PAEE) where errors ranging in the 100s of calories are the norm rather than the exception.

This leads the authors to the rather sweeping conclusion that,

“…self-reports of EI and PAEE are so poor that they are wholly unacceptable for scientific research on EI and PAEE. While new strategies for objectively determining energy balance are in their infancy, it is unacceptable to use decidedly inaccurate instruments, which may misguide health care policies, future research, and clinical judgment. The scientific and medical communities should discontinue reliance on self-reported EI and PAEE.”

While this may well hold true for research, I am not that sure about the implications for clinical practice.

This is because, the very act of self-monitoring has been shown to influence behaviour – irrespective of the precision of such monitoring (at least I am not aware of a single study showing that the accuracy of food records makes any difference to the outcome).

There is indeed overwhelming evidence that patients who use any form of self-monitoring (pen and paper or electronic) eat better and are more physically active than people who don’t.

While trying to determine someone’s precise energy balance by poring over these records is a rather futile exercise (the difference between the records and what actually happens may be in the 100s of calories), I do know that my patients who keep food and activity records do better than those who don’t.

Nevertheless, as far as research is concerned (or making clinical decisions based on assuming that the actual energy balance is anywhere close to the deceptively precise numbers calculated from such record), I agree with the authors that our current methods are highly inadequate and, what is worse, may well be misleading.

I, for one,happily ignore most of the data that comes from self-reported studies on diet or activity (which, incidentally is the vast majority of research on these issues), never mind that much of these data come from epidemiological studies, where any inference of causality is speculation at best.

On the other hand, precise or not, I do encourage all of my patients to self-monitor as I know this changes behaviour – no matter if these records are off by 100s of calories.

@DrSharma
Barcelona, Spain

ResearchBlogging.orgDhurandhar NV, Schoeller D, Brown AW, Heymsfield SB, Thomas D, Sørensen TI, Speakman JR, Jeansonne M, & Allison DB (2014). Energy balance measurement: when something is not better than nothing. International journal of obesity (2005) PMID: 25394308

 

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In The News

Diabetics in most need of bariatric surgery, university study finds

Oct. 18, 2013 – Ottawa Citizen: "Encouraging more men to consider bariatric surgery is also important, since it's the best treatment and can stop diabetic patients from needing insulin, said Dr. Arya Sharma, chair in obesity research and management at the University of Alberta." Read article

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