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Exenatide For Weight Loss In Hypothalamic Obesity

sharma-obesity-hypothalamusObesity caused by disruption of the hypothalamic centres that control body weight are among the most challenging forms of obesity to treat. Patients often experience relentless appetite with loss of satiety resulting in often dramatic weight gain. Causes can range from physical trauma to tumors that impact on the functioning of the hypothalamus.

Now, a study by Jefferson Lormenick and colleagues from Vanderbilt University, Nashville, Tennessee, published in OBESITY, describes the use of the GLP-1 analogue exenatide for weight loss in individuals with hypothalamic obesity.

The baseline weight of the 10 participants (7 female) was about 140 kg.

Overall, 8 individuals completed the 52 weeks of study.

Although the average weight loss of the entire group was not significant, 6 of the 8 participants, who did complete the 52 weeks of treatment, did lose about 6 kg.

While these results may sound disappointing, even this modest degree of weight loss in some patients, given the complexity of hypothalamic obesity, is remarkable, especially as participants were not offered any additional diet or lifestyle modification during the study.

It is also worth noting that untreated participants continued to gain weight over the study period.

As for the limitations of the study the authors also note that,

“Medication adherence was moderate and it is possible that long-acting GLP1RA could have better efficacy. HO is a heterogeneous disorder and better understanding of each patient’s hypothalamic damage may identify patients with improved responsiveness to GLP1RAs. The majority of our patients developed HO in childhood and longstanding obesity may be more refractory to treatment.”

Clearly, the use of GLP-1 analogues deserve further study for use in this patient population.

@DrSharma
Edmonton, AB

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Welcome To The International Congress on Obesity, Vancouver 2016

ICO2016This weekend sees the start of the XIII International Congress on Obesity (ICO), hosted by the World Obesity Federation in partnership with the Canadian Obesity Network (CON) in Vancouver, Canada.

As this year’s Congress President, together with World Obesity Federation President Dr. Walmir Coutinho, it will be our pleasure to welcome delegates from around the world to what I am certain will be a most exciting and memorable event in one of the world’s most beautiful and livable cities.

The program committee, under the excellent leadership of Dr. Paul Trayhurn, has assembled a broad and stimulating program featuring the latest in obesity research ranging from basic science to prevention and management.

I can also attest to the fact that the committed staff both at the World Obesity Federation and the Canadian Obesity Network have put in countless hours to ensure that delegates have a smooth and stimulating conference.

The scientific program is divided into six tracks:

Track 1: From genes to cells

  • For example: genetics, metagenomics, epigenetics, regulation of mRNA and non–coding RNA, inflammation, lipids, mitochondria and cellular organelles, stem cells, signal transduction, white, brite and brown adipocytes

Track 2: From cells to integrative biology

  • For example: neurobiology, appetite and feeding, energy balance, thermogenesis, inflammation and immunity, adipokines, hormones, circadian rhythms, crosstalk, nutrient sensing, signal transduction, tissue plasticity, fetal programming, metabolism, gut microbiome

Track 3: Determinants, assessments and consequences

  • For example: assessment and measurement issues, nutrition, physical activity, modifiable risk behaviours, sleep, DoHAD, gut microbiome, Healthy obese, gender differences, biomarkers, body composition, fat distribution, diabetes, cancer, NAFLD, OSA, cardiovascular disease, osteoarthritis, mental health, stigma

Track 4: Clinical management

  • For example: diet, exercise, behaviour therapies, psychology, sleep, VLEDs, pharmacotherapy, multidisciplinary therapy, bariatric surgery, new devices, e-technology, biomarkers, cost effectiveness, health services delivery, equity, personalised medicine

Track 5: Populations and population health

  • For example: equity, pre natal and early nutrition, epidemiology, inequalities, marketing, workplace, school, role of industry, social determinants, population assessments, regional and ethnic differences, built environment, food environment, economics

Track 6: Actions, interventions and policies

  • For example: health promotion, primary prevention, interventions in different settings, health systems and services, e-technology, marketing, economics (pricing, taxation, distribution, subsidy), environmental issues, government actions, stakeholder and industry issues, ethical issues

I look forward to welcoming my friends and colleagues from around the world to what will be a very busy couple of days.

For more information on the International Congress on Obesity click here

For more information on the World Obesity Federation click here

For more information on the Canadian Obesity Network click here

@DrSharma
Edmonton, AB

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Liraglutide Alters Brain Activity Related to Highly Desirable Food Cues

sharma-obesity-brainLiraglutide, a GLP-1 analogue now available for the treatment of obesity (as Saxenda) in North America, works by reducing appetite and increasing satiety, thus making it easier to lose weight and keep it off (with continuing treatment).

Now, a study by Olivia Farr and colleagues, in a paper published in Diabetologia not only present data showing the presence of GLP-1 receptors in human cortex, hypothalamus and medulla, but also provide functional evidence for altered  brain response to food cues.

After documenting the presence of GLP-1 receptor in human brains using immunohistochemistry, the researchers conducted a randomised controlled placebo-controlled, double-blind, crossover trial in 18 individuals with type 2 diabetes who were treated with placebo and liraglutide for a total of 17 days each (0.6 mg for 7 days, 1.2 mg for 7 days, and 1.8 mg for 3 days).

Using functional MRI neuroimaging studies, the researchers found that liraglutide remarkably decreased activation of the parietal cortex in response to highly desirable (vs less desirable) food images.

They also observed decreased activation in the insula and putamen, areas involved in the reward system.

Furthermore, using neurocognitive testing, the researchers showed that increased ratings of hunger and appetite correlated with increased brain activation in response to highly desirable food cues while on liraglutide.

In contrast, ratings of nausea (a well-known side effect of liraglutide) correlated with decreased brain activation.

As the authors note,

“Our data point to a central mechanism contributing to, or underlying, the effects of liraglutide on metabolism and weight loss.”

These findings no doubt match the reports from my own patients of experiencing less interest in highly palatable foods and finding it much easier to pass up on foods that they would have otherwise found hard to resist.

Clearly, as we learn more about brain function in eating behaviour, we are thankfully moving towards treatments that are clearly proving to be far more effective than just telling patients to “simply eat less” (which I have often likened to telling people with depression to “simply cheer up”).

@DrSharma
Edmonton, Canada

Disclaimer: I have received honoraria for speaking and consulting from Novo Nordisk, the maker of liraglutide

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Weight Loss With Liraglutide Improves Sleep Apnea

sharma-obesity-sleepapnea1The GLP-1 analogue liraglutide (Saxenda), recently launched in North America for the treatment of obesity, has now also been shown to improve symptoms (apnea-hypopnea index – AHI) of obstructive sleep apnea (OSA).

This, according to a paper by Blackman and colleagues published in the International Journal of Obesity.

This 32-week randomized, double-blind trial was conducted in about 360 non-diabetic participants with obesity who had moderate (AHI 15-29.9 events/h) or severe (AHI ⩾30 events/h) OSA and were unwilling/unable to use continuous positive airway pressure therapy (CPAP).

After 32 weeks, the mean reduction in AHI was greater with liraglutide (3.0 mg) than with placebo (-12.2 vs -6.1 events/h).

This improvement in sleep apnea was largely explained by the greater mean percentage weight loss compared with placebo (-5.7 vs -1.6%).

Additional findings included a greater reductions in HbA1c and systolic blood pressure in the participants treated with liraglutide versus placebo.

Liraglutide was generally well tolerated with no unexpected adverse effects.

Thus, it appears that in addition to weight loss, treatment with liraglutide 3.0 mg results in clinically meaningful improvements in the severity of obstructive sleep apnea, an important issue that affects both the cardiometabolic risk and quality of life of so many individuals living with obesity.

@DrSharma
Copenhage, DK

Disclaimer: I have received honoraria as a consultant and speaker for Novo Nordisk, the maker of liraglutide

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Overview of Obesity Management in Primary Care

sharma-obesity-doctor-kidGiven the vast number of individuals who could potentially benefit from effective long-term obesity management, there is no option but to manage most of this problem in primary care settings.

While this approach can be highly effective, it does require training, resources and ongoing (lifelong?) interventions (not unlike most other chronic diseases).

Now a rather comprehensive paper by Soleyman and colleagues from the University of Birmingham, Alabama, published in Obesity Reviews provides an overview of obesity management in primary care.

As readers are well aware, our body weight are tightly regulated by a complex neuroendocrine system and defends us agains weight loss through a multi-faceted physiological response to prevent further weight loss and restore body weight.

As the authors note,

“To maintain weightloss, individuals must adhere to behaviours that oppose these physiological adaptations and the other factorsfavouring weight regain. However, it is difficult for peoplewith obesity to overcome physiology with behaviour over the long term. Common reasons for weight regain include decreased caloric expenditure, decreased self-weighing frequency, increased caloric intake, increased fat intake and eating disinhibition over time.”

The paper provides a succinct overview of the evidence supporting behavioural, medical and surgical obesity treatments.

It also reiterates the basic principles of obesity management as outlined in the various guidelines:

1. Obesity is a chronic disease that requires long-term management. It is important to approach patients with information regarding the health implications.

2. The goal of obesity treatment is to improve the health of the patient, and it is not intended for cosmetic purposes.

3. The cornerstone of therapy is comprehensive lifestyle intervention from informed PCPs or other healthcare professionals.

4. The initial goal of therapy is a weight loss of 5–10% in most patients, as this is sufficient to ameliorate many weight-related complications. However, weight loss of ≥10% may be needed to improve certain weight-related complications, such as obstructive sleep apnoea.

5. Consideration should be given to the use of a weight-loss medication or possible bariatric surgery, as the addition of these treatment modalities to lifestyle therapy can promote greater weight loss and maintain the weight loss for a longer period of time.

6. It is important for clinicians to evaluate the patient for weight-related complications, that can be improved by weight loss, and to consider such patients for more aggressive treatment.

These recommendations (with minor variations) are also very much in line with the 5As of Obesity Management framework championed by the Canadian Obesity Network.

As for how to get more primary care clinics to actually implement these approaches, the authors note that,

“Primary care practitioners need to address the problem of obesity in their patients, just as they would with any other chronic condition such as hypertension or type 2 diabetes, and to ensure that their patients are aware of the health risks of obesity.”

Again something that the Canadian Obesity Network is working hard to promote in this country.

@DrSharma
Edmonton, AB

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