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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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The Highs and Lows of BMI and Mortality

sharma-obesity-dexa-scan1Almost all biological variables are detrimental to health at the extremes.

A blood pressure that is too high can kill you – so can a blood pressure that is too low.

A blood sugar that is too high can kill you – so can a blood sugar that is too low.

It turns out that BMI is no different – too high and too low both carry a risk – a risk, however, that is substantially confounded by actual body fat%, which is not reliably measured by BMI.

This is basically the message in a paper by my colleagues Raj Padwal and co from the University of Alberta in a paper published in the Annals of Internal Medicine.

The researchers looked at data from about 50,000 women and 5,000 men (mean age, 63.5 years; mean BMI, 27.0 kg/m2) referred for bone mineral density (BMD) testing with dual-energy x-ray absorptiometry (DXA), which they linked to administrative databases.

Given the size and demographics of the cohort, death occurred in almost 5000 women over a median of 6.7 years and 1000 men over a median of 4.5 years.

Women in the lowest BMI and body fat% quintiles had a 40% higher risk of dying (compared to quintile 3). Risk of dying were also about 20% greater in the highest body fat% quintile for women.

Similarly in men, both low BMI (HR, 1.45 for quintile 1) and high body fat percentage (HR, 1.59 for quintile 5) were associated with increased mortality.

The exciting bit about this study is that the researchers had both BMI and body fat% available to them and were able to show that both variables independently of each other contribute to mortality risk.

Thus, the worst possible combination in both men and women was low BMI and high body fat%.

Or, as the authors put it,

“Low BMI and high body fat percentage were both associated with increased all-cause mortality. Mortality increased as BMI decreased and body fat percentage increased…..Thus, our results suggest that BMI may be an inappropriate surrogate for adiposity, and this limitation may explain the presence of the obesity paradox in many studies.”

As the authors discuss, these finding should have clinical implications as they clearly demonstrate the limitations of BMI as a measure of health risk.

“..our findings underscore that the risk for all-cause mortality increases with both increasing adiposity and decreasing BMI in a general population of middle-aged and older adults. These findings also suggest the importance of using direct measures of adiposity when building prognostic or even exploratory models.”

@DrSharma
Edmonton, AB

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BMI Versus Fitness In Hypertension Risk

sharma-obesity-blood-pressureA higher BMI has long been associated with increased risk of hypertension (and there are many important physiological mechanisms at play to account for this relationship).

Now a study by Crump and colleagues published in JAMA Intern Medicine suggests that some of this risk may be mitigated by increased physical fitness.

The cohort study involving over 1.5 million Swedish young men in Sweden, who underwent standardized aerobic capacity, muscular strength, and BMI measurements obtained at a military conscription examination and were followed for up to 40 years.

Almost 100,000 men went on to develop hypertension, whereby both high BMI and low aerobic capacity (but not muscular strength) were associated with increased risk of hypertension, independent of family history or socioeconomic factors.

A combination of high BMI (overweight or obese vs normal) and low aerobic capacity (lowest vs highest tertile) was associated with the highest risk of hypertension.

The association with aerobic fitness was apparent at every level of BMI.

Form this study the authors conclude that high BMI and low aerobic capacity in late adolescence are associated with higher risk of hypertension in adulthood.

Although one must also be cautious in assuming causality with regard to associations found in such studies, the observations are certainly compatible with the notion that increased cardiorespiratory fitness may well mitigate some of the impact of increased BMI on hypertension risk.

@DrSharma
Edmonton, AB

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Severity Of Sleep Apnea Is Related To Distance From Sleep Centre

sharma-obesity-sleepapnea1Although sleep apnea is one of the most common and devastating complications of obesity, it remains woefully under-diagnosed and under-treated.

One factor accounting for this may well be the lack of timely access to sleep testing.

Now, a study by Hirsch Allen and colleagues from the University of British Columbia Hospital Sleep Clinic, published in the Annals of the American Thoracic Society, examined the relationship between severity of sleep apnea and travel times to the clinic in 1275 patients referred for suspected sleep apnea.

After controlling for a number of confounders including gender, age, obesity and education, travel time was a significant predictor of OSA severity with each 10 minute increase in travel time associated with an apnea-hypopnea-index increase of 1.4 events per hour.

The most likely explanation for these findings is probably related to the fact that the more severe the symptoms, the more likely patients are to travel longer distances to undergo a sleep study.

Thus, travel distance may well be a significant barrier for many patients accounting for a large proportion of undiagnosed sleep apnea – at least for milder forms.

Given the often vast distances in Canada one can only wonder about just how much sleep apnea goes under diagnosed because of this issue.

@DrSharma
Edmonton, AB

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