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

VN:F [1.9.22_1171]
Rating: 8.3/10 (3 votes cast)
VN:F [1.9.22_1171]
Rating: 0 (from 2 votes)


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

VN:F [1.9.22_1171]
Rating: 10.0/10 (2 votes cast)
VN:F [1.9.22_1171]
Rating: +1 (from 1 vote)


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

VN:F [1.9.22_1171]
Rating: 9.0/10 (2 votes cast)
VN:F [1.9.22_1171]
Rating: +1 (from 1 vote)


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

VN:F [1.9.22_1171]
Rating: 7.0/10 (1 vote cast)
VN:F [1.9.22_1171]
Rating: 0 (from 0 votes)


Friday, December 5, 2014

Hypothalamic Inflammation In Human Obesity

sharma-obesity-astrogliosisRegular readers may recall the exciting body of work from animal models of obesity showing that hypothalamic inflammation involving microscarring (gliosis) may play an important role in appetite and energy regulation in obesity.

Now, a study by Josep Puig and colleagues from the University of Girona, Spain, published in the Journal of Clinical Endocrinology and Metabolism, provides evidence for a similar process in humans.

The researchers used an MRI technique called diffusion tensor imaging (DTI) to measure hypothalamic damage in 24 consecutive middle-aged obese subjects (average BMI 43) and 20 healthy volunteers (average BMI 24).

Not only did the obese participants show greater signs of hypothalamic inflammation but these changes were also strongly associated with higher BMI, fat mass, inflammatory markers, carotid-intima media thickness, and hepatic steatosis and lower scores on cognitive tests.

While these studies do not prove cause and effect, these findings are consistent with findings in animal models and point to the role of pro-inflammatory pathways in the areas of the brain known to be intimately linked to appetite and energy regulation.

Understanding what exactly triggers this inflammatory response (in animal models, one fact appears to be a high-fat diet) and how this process could be inhibited, may open new avenues for obesity prevention and treatment.

@DrSharma
Madrid, Spain

ResearchBlogging.orgPuig J, Blasco G, Daunis-I-Estadella J, Molina X, Xifra G, Ricart W, Pedraza S, Fernández-Aranda F, & Fernández-Real JM (2014). Hypothalamic damage is associated with inflammatory markers and worse cognitive performance in obese subjects. The Journal of clinical endocrinology and metabolism PMID: 25423565

VN:F [1.9.22_1171]
Rating: 7.3/10 (4 votes cast)
VN:F [1.9.22_1171]
Rating: +1 (from 1 vote)

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

» More news articles...

Publications

"Conditions Presenting with Symptoms of Peripheral Arterial Disease."

» Browse and download more journal publications...

Watch Dr. Sharma in the News!

Dr. Sharma - NEWS Videos

Listen to Dr. Sharma!

Dr. Sharma - on CBC.ca

Watch Dr. Sharma on Listen Up


  • Subscribe via Email

    Enter your email address:

    Delivered by FeedBurner




  • Arya Mitra Sharma
  • Disclaimer

    Postings on this blog represent the personal views of Dr. Arya M. Sharma. They are not representative of or endorsed by Alberta Health Services or the Weight Wise Program.
  • Archives

     

  • RSS Weighty Matters

  • Click for related posts

  • Disclaimer

    Medical information and privacy
    Any medical discussion on this page is intended to be of a general nature only. This page is not designed to give specific medical advice. If you have a medical problem you should consult your own physician for advice specific to your own situation.


  • Meta

  • Obesity Links

  • If you have benefitted from the information on this site, please take a minute to donate to its maintenance.

  • Home | News | KOL | Media | Publications | Trainees | About
    Copyright 2008–2014 Dr. Arya Sharma, All rights reserved.
    Blog Widget by LinkWithin