Arya M. Sharma, MD

Regular readers of these pages will recall numerous posts on the profound effect of sleep deprivation on appetite and metabolism - a factor, believed by many, to be a major driver of the obesity epidemic (and not just in kids!).

Although epidemiological studies on sleep leave much to be desired both in quality and representativeness, current estimates suggest that we may be sleeping around two hours less than in the 60s.

Add to this the increase in night work, extended exposure to artificial light, and a increased eating in the late evening and night hours, and it is not hard to see how these changes would have affected our natural biology.

Enough reason for last month’s issue of Best Practices & Research Endocrinology and Metabolism to be entirely dedicated to the topic of Sleep and Metabolism.

As pointed out in the preface by Eve van Cauter and David Ehrmann from the University of Chicago, independent observations linking metabolism, sleep and circadian function include the idenfication of the orexin system which links the control of wakefulness with eating behavior, the identification of the circadian ‘Clock’ gene as conferring an increased risk of obesity and diabetes and the “sleep debt study” which showed that short term sleep restriction in healthy young adults results in decreased glucose tolerance (see previous blog entries on all of these landmark studies).

The special issue attempts to provide a comprehensive overview of this exciting field with contributions spanning from the molecular circuitry of hypothalamic pathways linking sleep and metabolism to the clinical relevance of sleep for nocturnal hypoglycemia in diabetic patients.

Readers may particularly be interested in the following articles in this issue:

Role of sleep duration in the regulation of glucose metabolism and appetite (Lisa Morselli et al.)

Sleep duration and cardiometabolic risk: A review of the epidemiologic evidence (Kristen L. Knutson)

Bariatric surgery and its impact on sleep architecture, sleep-disordered breathing, and metabolism (Silvana Pannain & Babak Mokhlesi)

The impact of sleep disturbances on adipocyte function and lipid metabolism (Josiane Broussard & Matthew J. Brady)

Sleep loss and inflammation (Janet M. Mullington, et al.)

Circadian disruption and metabolic disease: Findings from animal models (Deanna Marie Arble, et al.)

Sleep and the response to hypoglycaemia (Kamila Jauch-Chara & Bernd Schultes)

Sleep and metabolism: Role of hypothalamic neuronal circuitry (Asya Rolls, et. al.)

New evidence for a role of melatonin in glucose regulation (Elmar Peschke & Eckhard Mühlbauer)

Metabolic consequences of intermittent hypoxia: Relevance to obstructive sleep apnea (Luciano F. Drager, et al.)

I can only concur with the hopes of the editors that,

“… this volume will offer a thought provoking overview of this new area of investigation and inspire novel lines of research on the intriguing links between sleep, circadian function and metabolism and their impact on the health and well-being of billions of individuals in modern society.”

AMS
Acapulco, Mexico

Van Cauter E, & Ehrmann DA (2010). Preface. Best practice & research. Clinical endocrinology & metabolism, 24 (5) PMID: 21112018

Depression is a common finding in overweight and obese patients trying to lose weight. So is obstructive sleep apnea.

Unfortunately, the symptoms of sleep apnea can mirror those of major depressive disorder: tiredness and low energy levels, lack of interest and motivation to pursue your favourite activities, trouble with concentration, memory or decision making, and weight gain.

A paper by Mitsunari Habukawa and colleagues from the Kurume University School of Medicine, Fukuoka, Japan, just published online in Sleep Medicine, reminds us to screen overweight patients who do not respond adequately to antidepressant therapy for sleep apnea.

The authors describe 17 patients, who, despite pharmacotherapy for depression, continued having signs of major depressive disorder and were diagnosed with sleep apnea.

After two months of CPAP treatment for sleep apnea, their depression scores significantly improved.

Improvement in depression scores paralleled the reduction in sleepiness.

The results illustrate that patients with depression, who despite adequate pharmacotherapy continue having residual symptoms, should be screened for sleep apnea and treated if found positive.

An important corollary to this is that overweight and obese patients presenting with sleep apnea, should perhaps also be screened for signs of major depression.

Given the close association between excess weight, depression and sleep apnea, it is probably wise to regularly screen all patients presenting for obesity treatments for both conditions.

While simply treating depression and/or sleep apnea in people with excess weight is unlikely to result in significant weight loss, when present, both conditions can pose important barriers to successful weight management and must therefore be adequately addressed.

AMS
Edmonton, Alberta

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Habukawa M, Uchimura N, Kakuma T, Yamamoto K, Ogi K, Hiejima H, Tomimatsu K, & Matsuyama S (2010). Effect of CPAP treatment on residual depressive symptoms in patients with major depression and coexisting sleep apnea: Contribution of daytime sleepiness to residual depressive symptoms. Sleep medicine PMID: 20488748

Excess weight is commonly associated with sleep disordered breathing, of which obstructive sleep apnea is probably the most dangerous as it has been associated with daytime sleepiness, hypertension, insulin resistance, arrhythmias and sudden death.

One of the typical signs of obstructive sleep apnea is snoring - but, as it turns out, snoring is not always a sign of sleep apnea.

In fact, as I recently found out in an article published in Parkhurst Exchange, for the purposes of treatment, snoring can be divided into four categories:

1) mouth-breathing

2) nostril collapse

3) tongue base

4) palatal flutter

To make things a bit trickier, some patients may have more than one of these problems.

Fortunately, simple tests can help identify the problem (The following are taken directly from the Parkhurst publication):

Nostril collapse test: in front of a mirror, press the side of one nostril to close it. With the mouth closed, breathe in through the other nostril. If it tends to collapse, try propping it open with a paperclip. If breathing feels easier, nasal dilator strips are probably the answer, such as Breathe Right or Nozovent. Test both nostrils.

Mouth-breathing test: make a snoring noise with the mouth open. Then close the mouth and try to make the same noise. If you can’t, mouth breathing is the likely problem, and the likely solution is chin-up strips to hold the mouth closed, or an oral vestibular shield.

Tongue test: stick out the tongue and grip it between the teeth, then try to make a loud snoring noise. Failure is a sign of tongue base snoring. The treatment is a mandibular advancement device, which resembles a boxer’s mouthguard. There are expensive customized types, but ‘boil and bite’ moldable models can be just as effective.

Palatal flutter: this is vibration of the soft palate and uvula. There’s no test for it, but if the other tests are negative, it’s a likely culprit, especially in patients who aren’t overweight. The commonest treatment is Rhynil spray, made from the astringent herb Euphrasia officinalis.

I tried these test on myself but realised that I am not very good at making a snoring noise (at least not while awake).

Apparently, there is now some evidence that snoring, even without sleep apnea, can be associated with increased risk for car accidents.

And remember, snoring also puts your partner at risk, as they may also suffer increased ill-health as a result of disturbed sleep.

AMS
Edmonton, Alberta

Obstructive sleep apnea (OSA) is one of the most common respiratory problems in overweight and obese individuals. The poor quality of life, daytime somnolence, fatigue, memory loss, and increased risk for metabolic and cardiac complications makes OSA a significant health problem. Habitual snoring, witnessed apneas, or excessive daytime sleepiness should always prompt further investigation for OSA in anyone with overweight or obesity.

While more severe forms of OSA often require continuous positive airway pressure ventilation, milder forms may be amenable to even modest weight loss (higher degrees of weight loss resulting from bariatric surgery virtually cure OSA).

The effect of dietary weight loss was now for the first time tested in a randomized controlled trial in a new study just out in the American Journal of Respiratory and Critical Care Medicine.

In this study, Henri Tuomilehto and colleagues from the University of Kuopio, Finland, randomized 72 consecutive overweight patients (BMI 28-40) with mild OSA to a very low calorie diet (VLCD=600-800 KCal for 12 weeks) with supervised lifestyle counseling vs. routine lifestyle counseling (general oral and written information about diet and exercise).

While the VLCD group lost about 10% of their initial weight, the control group lost around 3%. The VLCD intervention resulted in a 75% reduced risk for OSA at the end of the year-long study. OSA was objectively cured in 63% of patients in the intervention group, but only 35% of patients in the control group. As expected, improvements in the apnea-hypopnea index (AHI) were strongly associated with changes in weight and waist circumference.

This study demonstrates that weight loss induced by a hypocaloric diet together with lifestyle counseling is feasible and effective in reducing symptoms in in the majority of subjects with mild OSA and that these outcomes are maintained at 1-year follow-up.

Indeed, these findings are very similar to the previous report of marked improvements in OSA in patients achieving an approximately 10% weight loss with sibutramine and lifestyle intervention published by Brendon Yee and colleagues from the University of Sydney in the International Journal of Obesity (2007).

Overall it appears that even a moderate 5-10% weight loss can lead to remarkable improvements in OSA - certainly an intervention worth considering prior to investing in an expensive CPAP machine. 

AMS
Edmonton, Alberta