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Why Short Term Weight Gain Can Be Easier to Lose Than Long Term Weight

>> Monday, March 12, 2018

No weight gained is easy to lose, but - have you ever wonder how Hollywood's actors can gain weight for a movie role, and the next thing you know, they are back at their usual weight for their next photo shoot?  While one may think that it’s simply the superstar access to personal chefs and trainers that gets actors back in shape, there is actually a physiologic basis that can make it less difficult to shed a quick/temporary/intentional weight gain than excess weight that has been present for the long term.

As discussed in a recent Scientific Statement on Obesity Pathogenesis by the Endocrine Society, obesity is associated with inflammation in various tissues, including muscle, fat tissue, vascular system, and liver, and this inflammation appears to be a consequence of chronic obesity.    There is also inflammation in the hunger/fullness centre of the brain, called the hypothalamus.

For a person who has been struggling with weight long term,  inflammation in these tissues causes maladaptive changes in those tissues that make them more resistant to weight loss.    It takes time for this inflammation to develop, so for a person who has had a fairly acute weight gain, it may be easier to drop pounds because they don't have this inflammation working against them.

So then you may wonder - why do some people seem to lose quickly gained weight more easily than others? (e.g. after pregnancy)?

Well, the story of the hunger/fullness centre in the brain is a little more complex.  It turns out that this inflammation may not only be a consequence of long term obesity, but may actually be present in some people before obesity develops.   Some animal studies suggest that eating a high fat diet triggers these inflammatory changes, damaging the neurons in the hypothalamus, which may then result in a disruption of sensations of hunger/fullness, lead to weight gain, plus make it harder to lose it again.

In other words, people who struggle to lose weight after a fairly quick/new weight gain may have inflammation in their hunger/fullness centre that was there before the weight gain, thus making them not only more prone to weight gain, but also making it harder to lose weight than the person without the inflammation. 

Follow me on twitter! @drsuepedersen © 2018


The Sleeping Beauty Diet

>> Monday, March 5, 2018

I was shocked and saddened to learn about yet another potentially harmful way that some people may be trying in a desperate attempt to lose weight.

The Sleeping Beauty diet involves taking sleeping pills, with the goal of sleeping through normal waking hours to avoid eating.  Also referred to as 'narcorexia', this fad is not only ineffective, but also dangerous:

1.  While it is true that not enough sleep is associated with higher body weight, so to is too much sleep.

2.  When you are sleeping, your body's metabolism is at its slowest.  When you are awake and moving around, you burn more calories.  Thus, people who sleep more than what their body needs are putting themselves at risk of weight gain by decreasing their overall calorie burn.

3.  Sleeping at unusual hours alters the body's circadian rhythm and the normal hormonal rhythm, which can has a negative impact on health from many perspectives.  Poor sleep quality caused by messing up the body's normal daily rhythm is associated with weight gain, due to alterations in the normal rhythm of hunger/fullness hormones, and an increase in craving for unhealthy foods.

4.  Most importantly: sedation induced by sleeping pills increases the risk of all manner of dangers  and problems due to impaired brain function while under the influence - car accidents, accidents at home, mistakes at home or the workplace... need I go on.

I am so terribly saddened that people out there are so desperate to lose weight that they are literally willing to sleep their life away to do it.  Yet another powerful and compelling reason why the health care profession, and society in general, needs to uniformly accept obesity as a chronic medical condition and help people get the support and care they so desperately need.

Follow me on twitter! @drsuepedersen © 2018


How Do Our Gut Bacteria Contribute To Obesity... And Can We Treat Them?

>> Monday, February 26, 2018

As blogged previously, we are learning that the bacteria we carry in our intestines (called the gut microbiota) have a role in obesity.  While we still seem to have more questions than answers on this topic, a fascinating review was just published, discussing some very interesting perspectives on this topic.  Here are some key points:

1.  We know there is an association between certain types of gut bacteria and obesity.  However, which is the 'chicken' and which is the 'egg', so to speak, is not clear, and the answer may be both.  In other words, there is evidence that certain types of gut bacteria contribute to the development of obesity, while others are protective.   There is also evidence that developing obesity can change the gut bacteria in favour of those that further contribute to obesity.

2.  Several ways that gut bacteria can contribute to obesity are identified:
  • some gut bugs are better at helping us extract calories from food by fermenting otherwise indigestible fibers
  • gut bacteria can influence permeability (leakiness) of the gut lining, allowing bacterial products into the bloodstream that can trigger an obesity-promoting low grade inflammatory response 
  • short chain fatty acids produced by gut bugs may have an effect on the gut's barrier function, as well as inflammation and appetite
  • (particularly fascinating in my opinion:) gut bacteria can have an impact on the genes we express in the hunger/fullness center in the hypothalamus in our brains through effects on inflammation and nerve signalling. 

3.  Can we treat obesity by changing our gut bacteria?

Knowing that some types of gut bacteria contribute to the development of obesity, the next natural question then is whether we can treat obesity by changing gut bacteria.

There is preliminary evidence that some strains of bacteria, provided as probiotic supplements, may be of benefit in weight management, but there is still much to learn in this area. There is also a lack of regulation in the supplement industry and a huge variation in what different probiotic supplements provide, so it can be hard to know what you're getting.  Some studies suggest that some fibres with prebiotic like effects may be beneficial as well.

Interestingly, metformin, which is an antidiabetic medication, has been shown to alter gut bugs in rodent studies in favour of a gut bacteria that is associated with less adiposity. (While metformin is considered to be weight neutral, some people do lose weight with it.) Also, metformin loses efficacy in animals when pretreated with antibiotics - could this be because of an alteration in gut bacteria? 

We also know that bariatric surgery changes the gut bug composition, and may play a role in the weight loss effect of surgery, by altering gut bugs in favour of those that are not so good at helping us harvest calories from food. 

Fecal transplant (yes, you read that correctly!) is also being considered as a possible treatment strategy for obesity.

Follow me on twitter! @drsuepedersen © 2018


New Obesity Medication Approved In Canada

>> Monday, February 19, 2018

Last week, Health Canada approved a new medication for weight management in Canada. This medication is actually a combination of two medications that have been around for years, called naltrexone and bupropion.

Bupropion is an antidepressant medication (called Wellbutrin), and is also used as a smoking cessation agent (called Zyban). It works by stimulating the fullness center of our brains, thereby suppressing appetite (specifically, it increases POMC activity in the hypothalamus by inhibiting reuptake of dopamine and norepinephrine).

Naltrexone is an opioid antagonist, which has been used for many years in the treatment of alcohol dependence and prevention of relapse to opioid dependence.  Naltrexone works by preventing the fullness center of our brains from shutting itself off, further contributing to appetite suppression (specifically: POMC releases B endorphin that creates a negative feedback loop by binding to the mu opioid receptor on POMC neurons; naltrexone blocks this negative feedback loop). 

Naltrexone and bupropion are also thought to have an effect on the mesolimbic reward center of our brains as well, which may result in decreased motivation for, desire for, and sense of reward/satisfaction from tasty foods. 

The weight loss at 1year with naltrexone/bupropion (trade name is Contrave) is about 4% of body weight compared to placebo, with people continuing to take the medication through a year (i.e. excluding those who dropped out of the study) losing 8.1% body weight in combination with lifestyle modification.  With an intensive weekly behavioural modification program, people who continued the medication and lifestyle program lost 11.5% weight after a year, again about 4% more than the behavioral modification group alone, who lost 7.3% body weight.

In a study of people with type 2 diabetes, overall weight loss was 3.7% body weight (5.9% in those who completed the trial) vs 1.7% in the placebo group (2.2% in trial completers). In addition, diabetes control improved, with a 0.5% greater reduction in hemoglobin A1C (a diabetes report card test) than placebo.

The dose of naltrexone/bupropion for weight management is gradually escalated from the starting dose of one 8mg/90mg tablet once a day, to the full dose of two tablets twice per day, over about 4 weeks.

The most common side effects of naltrexone/bupropion are nausea (in 32% of people vs 7% on placebo), constipation, dizziness, vomiting, and dry mouth.  Gastrointestinal side effects tend to abate after about 4 weeks on treatment.

In terms of rare but serious side effects, there is a slightly increased risk of seizures with bupropion (0.1% of people in the weight loss studies vs 0% on placebo), so this medication should not be used in people at risk of seizures.   It is advised not to take Contrave with a high fat meal, as this increases absorption of the medication to more than what was intended.  Also, if doses are missed, they should not be taken later (just skip it completely).

Though it is an antidepression medication, bupropion can temporarily worsen depression or suicidal thoughts (there were no suicide attempts in any of the naltrexone/bupropion weight loss studies).

Contrave should not be used in people who are on opioid pain medications.  There are also a number of other potential medication interactions that must be assessed before starting the medication.

Heart rate and blood pressure can increase slightly; what is usually seen is actually a very small decrease in blood pressure with the weight loss, but not as much blood pressure decrease as one would usually expect with the amount of weight loss seen.  A cardiovascular safety trial was begun but halted about halfway through because interim data had been released, with the concern being that this data release could impact the integrity of that trial.  Naltrexone/bupropion appeared to have cardiovascular safety at the halfway mark, but this is not sufficient data to answer the question – thus, another cardiovascular safety trial is being planned.

Note that this is not a comprehensive list of all considerations in prescribing naltrexone/bupropion – the full Canadian product monograph is available here

Naltrexone/bupropion was approved in USA in 2014 - interested readers can consult the American product monograph here.  

It is encouraging that we now have three medications in Canada that are approved for weight management.  We know that obesity is very heterogeneous (different in causes, contributors, and health consequences from person to person), and thus, the best approach will be unique to each individual.  We also know that the response to antiobesity medication differs from person to person.  The general principle is that a 5% weight loss after 3 months on treatment is the best predictor of long term success with a particular medication (though in my opinion,  maintaining weight after a significant dietary-induced weight loss with the help of medication is an important success as well).  

Disclaimer: I receive honoraria as a continuing medical education speaker and consultant from the makers of naltrexone/bupropion (Valeant). 

Follow me on twitter! @drsuepedersen © 2018


Exactly How Does Diabetes Medication Empagliflozin Save Lives?

>> Monday, February 12, 2018

The diabetes world was stunned and delighted in 2015 when the diabetes medication empagliflozin (Jardiance) was proven to reduce cardiovascular death by a whopping 38%.   This was an unexpected finding, as no diabetes medication had ever before been shown to decrease the risk of cardiovascular events.  The protective ability of empagliflozin starts very early, suggesting that it is not an effect on atherosclerosis (hardening of the arteries) per se, as this process takes a longer time. It has been a puzzle to understand exactly what is behind the protective abilities of empagliflozin.

A recent publication by Inzucchi and colleagues describes an analysis of the EMPA REG data to try to shed some light on this interesting question.  They conducted an exploratory mediation analysis, examining many different variables, to see which ones contributed to the CV event reduction.

They found that changes in hematocrit and hemoglobin mediated about half of the benefit of empagliflozin.  (This may be because a higher hematocrit means that there is less plasma volume, and/or increased oxygen delivery to the heart.)  Smaller mediation effects were seen for uric acid levels, fasting blood sugar, and A1C (a diabetes ‘report card’ blood test).   The combination of hematocrit, fasting blood sugar, uric acid, and protein in the urine (urine albumin:creatinine ratio) mediated most of the beneficial effect of empaglifozin.

So, we learn what we suspected - that there are multiple and complex mechanisms at play by which empagliflozin reduces cardiovascular risk. There may well be additional mechanisms at play that were not measured, or measurable, in the EMPA REG study.

Empagliflozin was the first type 2 diabetes medication that was shown to decrease the risk of cardiovascular events.  Its cousin in this class called SGLT2 inhibitors, canagliflozin (Invokana), has also been shown to protect against cardiovascular events, but canaglifozin was also found to increase the risk of amputations and bone fracture.  Two medications of a different class (GLP1 receptor agonists), called liraglutide (Victoza) and semaglutide (Ozempic) also have a protective benefit.

Disclaimer: I receive honoraria as as continuing medical education speaker and consultant from the makers of empagliflozin (Boehringer-Ingelheim and Eli Lilly), canagliflozin (Janssen), liraglutide and semaglutide (Novo Nordisk).  I am involved in research of SGLT2 inhibitors and GLP1 receptor agonists as treatments for diabetes. 

Follow me on twitter! @drsuepedersen © 2018



I am excited that you have arrived at my site, and I hope you are too - consider this the first step towards a Healthier New You!! As a medical doctor, Endocrinologist, and obesity specialist, I am absolutely passionate about helping people with weight management. Though there is certainly no magic cure for obesity, there IS a successful treatment plan out there for you - it is all about understanding the elements that contribute to your personal weight struggle, and then finding the treatment plan that suits your needs and your lifestyle. The way to finding your personal solution is to learn as much as you can about obesity: how our toxic environment has shaped us into an overweight society; the diversity of contributors to obesity; and what the treatment options out there are really all about. Knowledge Is Power!!

Are you ready to change your life? Let's begin our journey together, towards a healthier, happier you!!

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