Friday, July 18, 2014

Birth Control And Obesity

sharma-obesity-birth-control-pillAlthough obesity is a well-recognised factor for female infertility, the vast majority of women with excess weight are probably more interested in effective birth control.

That this is not as simple as it seems is evident from an article by Sheila Mody and Michelle Han from the University of California, San Diego, published in Clinical Obstetrics and Gynecaology.

The paper succinctly reviews a wide range of issues related to birth control and obesity.

To begin with, the authors points out that unintended pregnancies in obese women are often a problem simply because obese women are far less likely to use effective contraception than non-obese women. This non-use may in part be attributable to fear of weight gain, when most studies show that modern hormonal contraception is associated with almost no weight gain. The exception appears to be depot-medroxyprogesterone (DMPA), which may cause about 5 lb weight gain in the first year of use.

As for efficacy, the data show that unintended pregnancy rates among overweight women using oral contraceptives are similar or slightly higher than that among nonoverweight women. The reasons for these higher rates are not exactly clear.

Fortunately, the efficacy of intrauterine devices (IUD) appear no different between obese and non-obese women although the insertion of an IUD maybe more difficult in obese women because of poor visualization of the cervix and limited assessment of uterine position (a problem that can often be solved with the help of an ultrasound).

The paper also discusses the suitability of the vaginal vaginal contraceptive ring, which has been hypothesized to offer higher hormone levels for obese women than oral contraceptives because the hormones are absorbed directly into the vaginal mucosa and do not go through the first- pass liver metabolism.

Finally, the paper discusses issues around contraception for women who have undergone bariatric surgery (who have a particularly high rate of unintended pregnancies) as well as best practices for emergency contraception.

This is clearly information that all clinicians who counsel obese women should be aware of.

@DrSharma
Edmonton, AB

ResearchBlogging.orgMody SK, & Han M (2014). Obesity and Contraception. Clinical obstetrics and gynecology PMID: 25029338

 

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Thursday, July 17, 2014

Infant Antibiotic Exposure and Obesity Risk

sharma-obesity-gut-buts1With all the interest in the role of the gut bacteriome in the development of obesity, it was only a matter of time before someone examined the relationship between antibiotic use and obesity risk.

This is exactly what Anita Kozyrskyj and colleagues from the University of Alberta, Edmonton, Canada, explored in a paper now published in the International Journal of Obesity.

For their study they linked rovincial healthcare records to clinical and survey data from a Canadian longitudinal birth cohort study, whereby antibiotic exposure during the first year of life was documented from prescription records.

Overweight and central adiposity were determined from anthropometric measurements at ages 9 (n=616) and 12 (n=431) years.

According to this analysis, infants receiving antibiotics in the first year of life were about twice as likely to be overweight later in childhood compared to those who were unexposed.

However, after adjustment for birth weight, breastfeeding, maternal overweight and other potential confounders, this association persisted in boys but not in girls. The reason for this discrepancy is not clear.

Although these findings are in line with the notion that early use of antibiotics may predispose to obesity, it is important to not that these type of studies cannot prove causality.

It may well be that other non-measured factors could explain this association (e.g. overprotective or lower SES parents may be more likely to use antibiotics in their infants – both factors are independently associated with higher rates of obesity).

Nevertheless, given the rather high rates of antibiotic exposure in infants it appears that this may well be a promising area for further research not just in the context of obesity but also for many of the other conditions that are now believed to be influenced by intestinal flora.

@DrSharma
Edmonton, AB

ResearchBlogging.orgAzad MB, Bridgman SL, Becker AB, & Kozyrskyj AL (2014). Infant antibiotic exposure and the development of childhood overweight and central adiposity. International journal of obesity (2005) PMID: 25012772

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Friday, July 11, 2014

Is Weight Gain Typical in Atypical Depression?

sharma-obesity-depressionDepression or major depressive disorder (MDD) is not only one of the most common psychiatric problems, it also comes in many flavours.

While melancholic or “typical” depression is characterized by a loss of pleasure in most or all activities (anhedonia), a failure of reactivity to pleasurable stimuli, psychomotor retardation and a strong sense of guilt, “atypical” depression is characterized by mood reactivity (paradoxical anhedonia), excessive sleep or sleepiness (hypersomnia), a sensation of heaviness in limbs, and significant social impairment as a consequence of hypersensitivity to perceived interpersonal rejection.

An important further distinction is that “typical” depression is commonly associated with loss of appetite and weight loss, whereas “atypical” depression typically involves increased appetite (comfort eating), often with significant weight gain.

Now a study by Aurélie Lasserre and colleagues from Switzerland, published in JAMA Psychiatry, looks at the risk for weight gain in patients with different forms of depression.

The prospective population-based cohort study, included 3054 randomly selected residents of the City of Lausanne (mean age, 49.7 years; 53.1% were women) with 5.5 years of follow-up.

Depression subtypes according to the DSM-IV, as well as sociodemographic characteristics, lifestyle (alcohol and tobacco use and physical activity), and medication, were elicited using the semistructured diagnostic interviews.

As expected, only participants with the “atypical” subtype of MDD at baseline had a higher increase in adiposity and were about 3.75 times more likely to have developed obesity during follow-up than participants without MDD.

This association remained robust even after adjustment for a wide range of confounders.

Thus, as the authors note,

The atypical subtype of MDD is a strong predictor of obesity. This emphasizes the need to identify individuals with this subtype of MDD in both clinical and research settings. Therapeutic measures to diminish the consequences of increased appetite during depressive episodes with atypical features are advocated.

Although we should be wary of those antidepressants that can cause weight gain, an early diagnosis and treatment of atypical depression may well prevent further weight gain and perhaps facilitate weight loss in patients with atypical depression.

Clearly, screening for “atypical” depression must be an essential part of obesity assessment and management.

@DrSharma
Edmonton, AB

ResearchBlogging.orgLasserre AM, Glaus J, Vandeleur CL, Marques-Vidal P, Vaucher J, Bastardot F, Waeber G, Vollenweider P, & Preisig M (2014). Depression With Atypical Features and Increase in Obesity, Body Mass Index, Waist Circumference, and Fat Mass: A Prospective, Population-Based Study. JAMA psychiatry PMID: 24898270

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Thursday, June 12, 2014

Lack of Oxygen Can Trigger Adipose Tissue Inflammation

sharma-obesity-adipocytes3Lack of oxygen is a well known stressor for any living cell – this is of course also true for fat cells (adipocytes).

But lack of oxygen does not just occur when there is a problem with breathing or blood flow. Lack of oxygen (hypoxia) can also occur a the cellular level, when the cellular oxygen demand exceeds supply.

According to what may well be considered  a “landmark” paper by Lee and colleagues, published in CELL, it appears that increased adipocyte oxygen consumption may be the key trigger of molecular changes that cause local inflammation and systemic insulin resistance commonly associated with obesity.

The paper reports on a series of animal studies with diet-induced obesity (through a high-fat diet), demonstrating that with increasing weight gain, adipocyte respiration in the mitochondria becomes “uncoupled” leading to a significant increase in oxygen consumption with relative hypoxia.

This uncoupling appears to be mediated through activation of adenine nucleotide translocase 2 (ANT2), an inner mitochondrial membrane protein, by saturated fatty acids.

The resulting hypoxia, in turn, activates the transcription factor HIF-1α, setting off a pro-inflammatory response which in turn leads to insulin resistance with an increased risk of diabetes.

The researcher also show that blocking either ANT2 or HIF-1α can prevent these events, thereby suggesting new pharmacological targets for alleviating the pro-inflammatory and metabolic consequences of obesity.

Obviously, there is always room for caution in extrapolating animal findings to humans, but this paper is likely to spawn a flurry of similar work in human fat cells.

As cellular hypoxia is more likely to occur the larger the fat cell, these studies also tie in the previous observations of a positive association between adipocyte cell size and metabolic abnormalities.

Certainly a topic we can expect to hear more of in the not too distant future.

@DrSharma
Edmonton, AB

ResearchBlogging.orgLee YS, Kim JW, Osborne O, Oh da Y, Sasik R, Schenk S, Chen A, Chung H, Murphy A, Watkins SM, Quehenberger O, Johnson RS, & Olefsky JM (2014). Increased Adipocyte O2 Consumption Triggers HIF-1α, Causing Inflammation and Insulin Resistance in Obesity. Cell, 157 (6), 1339-52 PMID: 24906151

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Monday, June 2, 2014

There Has Not Been A Single Success Story in National Obesity Prevention in The Past 33 Years

sharma-obesity_global_obesity_mapJust back from the 21st European Congress on Obesity, I missed out on 100s of media interviews I could have done last week as the media were abuzz with the latest obesity statistics from around the world.

In what will clearly be considered a “landmark” paper by ~150 authors published in The Lancet, we now have the latest summary of global, regional and national data on obesity.

Based on the analyses of almost 1800 surveys, reports, and published studies, the worldwide prevalence of adults with a body-mass index (BMI) of 25 kg/m2 or greater increased between 1980 and 2013 from 29 6o 37% in men and from 30 to 38% in women.

In 2013, 23% of children and adolescents in developed countries were overweight or obese while the same is true for about ~12% of kids in developing countries.

Together, this leave about 2.1 billion of the world populations as currently overweight or obese with numbers growing in virtually every region of the world (albeit with a bit of a slow down in developed countries).

Thus, the authors conclude that,

Not only is obesity increasing, but no national success stories have been reported in the past 33 years.

Obviously, there are many reasons why we lack success stories.

No doubt, one could point to governments that have not tried hard enough, or the food and leisure industry that sustains its overwhelming influence on consumer “choices”, or the continuing “westernization” of global lifestyles.

No doubt, many policies have been tried (e.g. fat taxes, menu labelling, school food programs, fitness taxes, BMI report cards as well as more drastic “shame and blame” tactics) but conclusive evidence that any such measures are working to reverse the tide remains elusive.

It may well be that the flattening of obesity (but not severe obesity) rates in developed countries may have more to do with the “natural” history of this epidemic, than with any public health measures.

On the other hand, perhaps the reason so little progress has been made in preventing obesity is that we are not going after the right targets, namely to change the actual life experiences of overworked, sleep deprived, stress-out families living in a culture of “grabbing a bite” and “working lunches” at one end and the millions living with poor education and food insecurity at the other. No amount of fiddling with menu labelling is about to change that.

What is sad in all of this is the simple fact that virtually no government has yet developed a comprehensive plan on how to improve access to obesity treatments for its populations. Rather, overweight and obese people the world over continue to be denied medical care for this disease on the simple basis that it is their own “fault”.

So while the world awaits the wonder of “prevention” to hopefully one day work its magic, millions of people around the world continue struggling on their own with no help in sight.

Let me guess what will happen as a result of these new numbers – not much!

@DrSharma
Edmonton, Alberta

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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

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