Monday, January 26, 2015

Endocrine Society Clinical Practice Guidelines For The Pharmacological Treatment of Obesity

sharma-obesity-medications6Last week, the US Endocrine Society released a rather comprehensive set of evidence-based clinical practice guidelines for the pharmacological management of obesity, published in the Journal of Clinical Endocrinology and Metabolism.

The recommendations in the 21-page document follow the rather rigorous Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) group (from 0 to 4 stars) and goes beyond just evaluating the evidence in favour of pharmacological treatment of obesity itself but also for the pharmacological treatment of overweight and obese individuals presenting other medical conditions.

Here are the (in my opinion) most important recommendations from this document:

1) While diet, exercise and behavioural interventions are recommended in all patients with obesity,

“Drugs may amplify adherence to behavior change and may improve physical functioning such that increased physical activity is easier in those who cannot exercise initially. Patients who have a history of being unable to successfully lose and maintain weight and who meet label indications are candidates for weight loss medications.(****)”

2) “If a patient’s response to a weight loss medication is deemed effective (weight loss > 5% of body weight at 3 mo) and safe, we recommend that the medication be continued. If deemed ineffective (weight loss < 5% at 3 mo) or if there are safety or tolerability issues at any time, we recommend that the medication be discontinued and alternative medications or referral for alternative treatment approaches be considered. (****)”

3) “If medication for chronic obesity management is prescribed as adjunctive therapy to comprehensive life- style intervention, we suggest initiating therapy with dose escalation based on efficacy and tolerability to the recommended dose and not exceeding the upper approved dose boundaries. (**)”

The guidelines also make specific recommendations for the pharmacological treatment of overweight and obese individuals presenting with a wide range of other medical issues, including 2 diabetes mellitus (T2DM), cardiovascular disease, psychiatric illness, epilepsy, rheumatoid arthritis, COPD, HIV/AIDS and allergies.

For example:

“In patients with T2DM who are overweight or obese, we suggest the use of antidiabetic medications that have additional actions to promote weight loss (such as glucagon-like peptide-1 [GLP-1] analogs or sodium-glu- cose-linked transporter-2 [SGLT-2] inhibitors), in addi- tion to the first-line agent for T2DM and obesity, metformin. (***)”

The guidelines also discuss the pros and cons of the anti-obesity medications currently available in the US (phentermine, orlistat, phentermine/topiramate, lorcaserin, buproprion/naltrexone, and liraglutide), which we can only hope will soon also become available to patients outside the US.

The entire document is available here.

@DrSharma
Edmonton, AB

VN:F [1.9.22_1171]
Rating: 8.7/10 (3 votes cast)
VN:F [1.9.22_1171]
Rating: +2 (from 2 votes)


Wednesday, January 21, 2015

Activity Trumps Weight Loss For Health?

Despite the sharma-obesity-exercise2The fact that it is better to be fit and fat than skinny and unfit is not new – indeed, I would regard the evidence on this as pretty conclusive.

Nevertheless, for those, who still harbour any remaining doubts, the study by Ulf Ekelund on behalf of the EPIC Investigators, recently published in the American Journal of Clinical Nutrition should drive this message home.

This analysis looks at the relationship between physical activity and all-cause mortality in 334,161 European men and women followed for about 12.4 y (corresponding to 4,154,915 person-years).

No matter how the researchers looked at the data, activity levels appeared a better predictor of mortality than BMI or waist circumference.

Thus the authors calculated that while avoiding all inactivity would theoretcally reduce all-cause mortality by 7.35%, trying to maintain a “normal weight” (or rather a BMI less than 30) would reduce mortality by only 3.66% (although avoiding obesity AND inactivity did have the greatest effect).

Despite the limitations of these type of cross-sectional analyses, which as a rule, tend to overestimate the potential benefits of an actual intervention, the message is clear – it appears that even small increases in physical activity in inactive individuals can have substantially greater benefits to health than obsessing about losing a few pounds.

This is indeed useful information, as we have long known that increasing physical activity in most cases does surprisingly little in terms of weight loss but rather a lot in terms of increasing health and fitness.

So do not despair if the hours your patients are putting in at the gym are not changing those numbers on the scale – the health benefits are still worth the effort.

@DrSharma
Reykjavik, Iceland

VN:F [1.9.22_1171]
Rating: 10.0/10 (4 votes cast)
VN:F [1.9.22_1171]
Rating: +4 (from 4 votes)


Monday, January 19, 2015

Sleep Apnea And Quality Of Life In Iceland

Laugarvatn Fontana Geothermal Baths, Iceland

Laugarvatn Fontana Geothermal Baths, Iceland

This week, I am in Reykjavik on behalf of the Icelandic Medical Association to speak at their 2015 Annual Conference.

Despite its proverbial rugged outdoorsy lifestyle with ample time spent in natural hot spring spas and saunas (both of which I enjoyed yesterday, thanks to my excellent hosts), Iceland has a significant obesity problem of its own – reason enough for this problem to be taken seriously (I will be meeting with the Icelandic health minister and his staff to discuss this issue later this week).

There is indeed a small but active obesity research community in Iceland with growing experience in the management of this disease.

One important contribution, for e.g. is the recent paper by Erla Bjornsdottir and colleagues from the University of Iceland, published in the Journal of Sleep Research, that examines the impact of two years of treatment vs. non treatment of moderate to severe obstructive sleep apnea (OSA) on quality of life in over 800 overweight or obese individuals newly diagnosed with this condition.

The comparator group consisted of 750 randomly selected Icelanders. The researchers also compared users and non-users of CPAP treatment within the individuals diagnosed with sleep apnea.

Overall, as one might expect, the quality of life (measured by the SF-12 questionnaire) of untreated individuals with OSA was markedly worse that of the general population, even when matched for age, body mass index, gender, smoking, diabetes, hypertension and cardiovascular disease.

Surprisingly, however, despite a positive trend towards improvement in physical quality of life from baseline to follow-up in users and the most obese individuals, there were no significant overall differences between full and non-users.

This is particularly surprising as I have often seen dramatic changes in the quality of life and general well-being in patients with OSA, who started on CPAP treatment in my practice (but I guess anecdotes are always tempered by averages).

Based on their findings, the researchers conclude that the co-morbidities of obstructive sleep apnea, such as obesity, insomnia and daytime sleepiness (often not fully controlled by CPAP), appear to have a substantial effect on life qualities and may need to be taken into account and addressed with additional interventions.

The message here, I believe, is that despite its effectiveness for better control of breathing, simply putting patients on CPAP and hoping for the best may not be quite enough to improve the substantially reduced quality of life associated with this disorder.

@DrSharma
Reykjavik, Iceland

VN:F [1.9.22_1171]
Rating: 0.0/10 (0 votes cast)
VN:F [1.9.22_1171]
Rating: +1 (from 1 vote)


Friday, January 16, 2015

The Physiological Benefits Of Laughter

theater_masksAs regular readers are well aware, over the past year, I have been exploring the use of stand-up comedy in communicating about the science of obesity to anyone who cares to listen.

While preparing for this new venture included working with professional comedians, taking improv classes, and, yes, impromptu appearances at local “open-stages”, I have also delved into the (sometimes rather serious) literature on the science of comedy and laughter.

Indeed, as one may suspect, there is indeed a rather large and growing body of scientific literature on humor, comedy and laughter – including its physiological and psychological effects, its therapeutic use (in everything from depression and chronic pain to cancer and obesity), and as a communication tool for health professionals.

Anyone interested in this topic, may wish to refer to a recent article by Dexter Louie and colleagues from the University of California, Harvard Medical School and the Joslin Diabetes Centre on laughter as a tool for lifestyle medicine that recently appeared in the American Journal of Lifestyle Medicine (btw – a term that I really don’t like).

The article begins with a brief discussion of the three preeminent theories (out of over 100 competing ideas) of why we laugh, which are summarized as follows (the examples are mine):

1. Release theory, which argues that laughter is the physical manifestation of repressed desires and motivations (which explains potty jokes).

2. Superiority theory, which posits that laughter is a means of increasing one’s self-esteem at the expense of others (which is probably why most people laugh at fat jokes).

3. Incongruity theory, which states that humor is created by a sense of incongruity between two or more objects within a joke (e.g. an obesity doctor making jokes about obesity doctors).

The article then goes on to briefly review the physiological effects of laughter, whereby it makes a clear distinction between spontaneous and and self-induced laughter:

“The former refers to “genuine” or unforced laughter, often in response to a stimulus, whereas the latter describes laughter that is simulated de novo. Spontaneous laughter is often associated with positive mood, whereas simulated laughter is primarily physical and is not necessarily associated with positive emotions or feelings. Neuroimaging suggests that different neural pathways are used in these 2 forms of laughter.”

The researchers review a range of studies documenting the positive effects of spontaneous laughter on stress hormones, endorphins, immune response, pain tolerance, anxiety as well as studies showing that the cardiovascular response to a good laugh are virtually identical to those elicited by a bout of physical exercise (exercise physiologists take note!).

Despite these promising findings, the authors are also quick to point out that,

“There is great potential for future research in laughter. Randomized controlled large-scale trials are needed to further elucidate the physiologic effects of laughter.”

In the second part of the article, the authors discuss whether or not physicians should use humor as a tool to induce therapeutic laughter?

“Of course, health is a serious and often grave matter, and humor delivered at inappropriate times can be devastating, insensitive, and crass……Within the bounds of appropriateness, however, both humor and laughter can be beneficial. For one, laughter shared between the provider and patient conveys a measure of trust and light-heartedness. Furthermore, humor can improve communication, as a joke can signal a transition in the conversation from the serious to more benign topics.”

The authors even have suggestions on how to address the issue of laughter in clinical practice:

“Providers can ask, “What has made you laugh recently?” or “How often do you laugh?” Inquiring about laughter opens the door to light heartedness and also could lead to counseling on laughter and sharing the latest research with the patient. More important, it allows the provider to determine what the patient finds funny, thereby allowing the provider to tailor recommendations to better fit the patient’s needs and preferences. This also contains the potential to deepen the therapeutic relationship between patient and provider. Put together with a more structured approach, the health care provider could consider prescribing laughter to patients.”

And here is what a laughter prescription could look like (directly borrowed from exercise prescriptions):

(F) Frequency: once a week
(I) Intensity: belly laughing
(T) Time: 30 minutes

(T) Type: your favorite sit-com

While much remains to be studied in terms of the therapeutic use of laughter (e.g. spontaneous vs. self-induced, individual vs. group laughter, dose-response relationships, laughter yoga, etc.), as the authors point out, there is an increasing body of evidence pointing to potential benefits for health and well-being.

Or, as the authors put it,

“With no downsides, side-effects, or risks, perhaps it is time to consider laughter seriously.”

@DrSharma
Edmonton, AB

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


Tuesday, January 13, 2015

Leptin Mediates Obesity Hypertension – End Of Story!

sharma-obesity-obese_miceSome times you think that a scientific question has long been adequately answered when someone comes along and puts any remaining doubts to rest.

This happened last week, when Stephanie Simonds and an international group of researchers, in a paper published in Cell, present a rather elegant and sophisticated range of studies clearly demonstrating that the adipocyte-derived hormone leptin is a key mediator of hypertension in diet-induced (and probably other types of) obesity.

The reason I thought that this question had already long been put to rest was due to a series of rather convincing animal and human studies published in the early 2000s (some of which I was directly involved in) that nicely demonstrated a) that obesity in hypertension is largely mediated by an increase in (renal) sympathetic activity; b) that leptin stimulates sympathetic activity and sodium retention; c) in dogs and humans leptin concentrations are closely correlated with sympathetic nerve activity and blood pressure. We’ve also known that obese mice lacking leptin or its receptor do not develop hypertension despite considerable weight gain.

If anyone should have any remaining questions, these are now answered in the paper by Simonds and colleagues which uses an array of experiments involving animals deficient in leptin or leptin receptors, humans with loss-of-function mutations in leptin and the LepR and show that leptin’s effects on blood pressure are mediated by neuronal circuits in the dorsomedial hypothalamus (DMH), an effect that is prevented or reversed by blocking leptin with a specific antibody, antagonist, or inhibition of the activity of LepR-expressing neurons in the DMH. 

All of this is interesting and highlights the fact that adipose tissue is far more than a simple storage organ for fat but rather a tissue that plays an active role in the regulation of a wide range of bodily functions.

Leptin alone, just one of the many hormones secreted by fat cells (often collectively referred to as adipokines), has been shown to play an important role in appetite and energy regulation, immune function and bone development.

As for bringing us a step closer to obesity treatments, the study suggests that it may not be easily possible to harness leptin as a treatment for weight loss, as one expected side effect would be an increase in blood pressure and heart rate – effects that have limited the clinical tolerability of other “sympathomimetic” drugs.

@DrSharma
Edmonton, AB

VN:F [1.9.22_1171]
Rating: 0.0/10 (0 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

  • 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 2008–2015 Dr. Arya Sharma, All rights reserved.
    Blog Widget by LinkWithin