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How Weight Loss Affects Different Body Tissues, Fat Genes, And Inflammation

>> Saturday, March 24, 2018


(this is fat tissue under a microscope)



We know that a 5-10% weight loss improves many health conditions associated with obesity.  However, it is very interesting to note that some health issues like blood sugar starts to improve with as little as 2-3% weight loss, whereas other health issues like sleep apnea require closer to 10% weight loss before we start to see improvements.  Why is this?


An eloquent study helps us to understand how different tissues in our body respond to weight loss.  This was a randomized controlled clinical trial, assigning 40 patients to a target 0%, 5%, 10%, or 15% weight loss, and then conducted an array of testing to understand the metabolic changes that occur at each of these degrees of weight loss.  Testing was extensive and included assessment of body composition, 24h blood pressure monitors, blood testing for metabolic parameters and inflammatory markers, tests of organ-specific insulin sensitivity, and even biopsies of fat tissue. Participants were weight stable for at least 3 weeks before testing was conducted.

Key findings were truly fascinating.

After a 5% percent weight loss:
  • There was a decrease blood sugar, insulin levels, triglycerides, ALT (liver test)
  • systolic blood pressure decreased (the top number), but not diastolic (bottom number)
  • NO effect on good cholesterol (HDL), bad cholesterol (LDL), glucose tolerance test (OGTT)
  • improvement in insulin sensitivity in fat, liver, skeletal muscle 
  • improvement in beta cell function (the cells in the pancreas that make insulin)

After 11% weight loss: (the 10% group ended up losing 11%)
  • continued reduction in insulin and triglycerides 
  • altered gene expression in subcutaneous fat tissue - including genes involved in fat synthesis, cholesterol flux, and inflammation
  • no additional benefit to insulin sensitivity in fat tissue or liver
  • additional improvement in insulin sensitivity in skeletal muscle
  • additional improvement in beta cell function

After 16% weight loss: (the 15% group ended up losing 16%)
  • reduction in inflammatory markers (plasma free fatty acids, CRP)
  • more marked altered gene expression in subcutaneous fat tissue - including genes involved in fat synthesis, cholesterol flux, and inflammation
  • continued reduction in insulin and triglycerides
  • no additional benefit to insulin sensitivity in fat tissue or liver
  • additional improvement in insulin sensitivity in skeletal muscle
  • additional improvement in beta cell function

So what is the BOTTOM LINE from this (rather complicated) study?   

1. A 5% weight loss has important benefits to our health, primarily related to a decrease in our body's resistance to insulin.  

2. Further weight loss continues to improve our body's insulin resistance (particularly in muscle), with additional improvements in our metabolic health.  

3.  At 11% weight loss, we start to see changes in how our fat tissue expresses genes, in favour of better health.

4.  At 16% weight loss, there is a decrease in inflammation in our bodies, and a more marked change in fat tissue gene expression.

While a smaller degree of weight loss (even just 2-3% based on other studies) has a very important impact on our metabolic health, the changes in inflammation and fat gene expression seen at over 10% weight loss may well be what it takes to see benefits in other medical conditions associated with obesity, such as obstructive sleep apnea and arthritis.


Follow me on twitter! @drsuepedersen

www.drsue.ca © 2018

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How Your Diet Influences Where You Lose Fat

>> Sunday, March 18, 2018




In weight management, our goal is to improve overall health.  In a perfect world, it would be preferable if we could melt away the fat around and inside the internal organs (called 'visceral fat') rather than the fat under the skin, as it is this visceral fat that contributes most to health complications of obesity such as diabetes, high blood pressure, and metabolic syndrome.

A recent study suggests that what we eat actually can help us to target this visceral fat.

The CENTRAL study, published in the journal Circulation, randomized 278 sedentary adults with either abdominal obesity or high cholesterol to follow either the Mediterranean diet versus a low fat diet for 18 months.  Six months into the trial, participants were also randomized to follow an exercise program or not. They used MRI scans to evaluate fat under the skin, fat around the organs, fat in the liver, pancreas, and even around the heart.

At the end of the 18 month study, weight loss was the same between all four groups (Mediterranean vs low fat diets, with or without exercise) at -3.2%.   However, where fat was lost from, and how this influenced health, was different between groups:


  • People on the Mediterranean diet lost more fat from the liver, pancreas, and around the heart. 
  • Exercise with either diet had a greater effect on reducing visceral fat. 
Whether or not total body weight was lost: 
  • Losing visceral fat and/or liver fat improved cholesterol.
  • Losing fat deep under the skin improved insulin sensitivity.
  • Losing fat just under the skin had no effect on health and reduced levels of leptin (a hormone that tells our brains that we feel full). 
The findings that the Mediterranean diet preferentially reduces the more dangerous visceral fat may explain why it is the only diet that has been convincingly found to prevent cardiovascular events.  

These results also show us that it's not about numbers on the scale, as this does not reflect the important changes going on with fat deposit patterns inside. 



Follow me on twitter! @drsuepedersen

www.drsue.ca © 2018

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

>> Sunday, March 11, 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

www.drsue.ca © 2018

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

>> Sunday, February 25, 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


www.drsue.ca © 2018

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Could Your Cholesterol Medication Cause Diabetes?

>> Thursday, January 25, 2018




With any medication, there are benefits and risks that need to be considered.  Medications are generally recommended to a patient when the potential benefit of the medication is felt to be greater than the potential risks.

While it is extremely important for both doctors and patients to be well informed of potential side effects of medications, the media unfortunately loves to hype up side effects, often making it seem like the risks of taking a medication must outweigh any potential benefits.

Statins, a group of cholesterol medications, have taken a particular beating in the media over the years.   A colleague of mine approached me not too long ago saying that he was worried about his patients being afraid of taking their statin cholesterol medications because of fear of developing diabetes as a side effects, and asked me if I would publish a post on this topic.

An excellent review was published in The Lancet, which does a great job of addressing the question of benefit vs risk of statin therapy.

If 10,000 people are treated with statin therapy for 5 years: (with the example given of 40mg of atorvastatin (Lipitor) daily)

Benefits:
  • if these 10,000 people had a past history of 'blocked arteries' (occlusive vascular disease) - eg prior heart attack or stroke: 1,000 would be saved from another heart attack or stroke
  • if these 10,000 people had no history of vascular disease: 5,000 would be saved from a heart attack or stroke

Risks: 
  • 50-100 will develop diabetes because of their statin
  • 5-10 will have a bleeding type (hemorrhagic) stroke
  • 5 will develop serious muscle complications


The risk of developing diabetes due to statin medications is higher with the more powerful statins (atorvastatin (Lipitor) and rosuvastatin (Crestor)), and with higher doses.  However, it is precisely these particular statins at the higher doses that have the biggest benefit to prevent heart attacks and strokes in people who have a past history of vascular disease.

People with risk factors for developing diabetes (eg, prediabetes, obesity) are at higher risk of statins tipping them up into diabetes range blood sugars. However, even if a person develops diabetes due to their statin, the health benefit in preventing heart attacks and strokes is much greater than the adverse effect of diabetes on their health, provided the diabetes is well managed.

For people who already have diabetes, statins also have a powerful benefit in preventing heart attacks and strokes, which is felt to far outweigh any small increase in blood sugars that may occur (and can be managed with adjustment to diabetes medication).

As to how statins increase the risk of developing diabetes, another study in The Lancet suggests that it may be related to the mechanism of statins to inhibit an enzyme called HMG CoA reductase, and may be genetically mediated.


Follow me on twitter! @drsuepedersen

www.drsue.ca © 2018

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Is Your Doctor NOT Talking Nutrition?

>> Thursday, January 18, 2018




Everyone out there: I would like you to raise your hand if your doctor has NOT recently talked to you about good nutrition.  If you have your hand up, you are not alone - only about 12% of office visits include counselling about diet, despite there almost always being a good reason to talk about nutrition (eg diabetes, obesity, high blood pressure, and so forth).

Doctors out there - do you feel like you don't do a great job in counselling your patients on good nutrition?   If so, you are definitely not alone.

A recent Viewpoint paper published in the Journal of the American Medical Association uncovers some important issues that limit good nutritional counselling in the doctor's office.

Issues cited that limit doctors in providing nutritional counselling:
  • Doctors receive very little nutritional training in medical school. 
  • Limitations of time in an appointment. 
  • Limitations in reimbursement (pay) for doctors to provide nutrition counselling.
  • Frustration in trying to counsel on healthy food choices when our environment is so full of unhealthy choices.
Here are some easy steps that clinicians can take to improve nutritional counselling: 

1. Start the conversation - check out this easy to use tool, which contains eight quick and easy questions you can ask, with suggestions for reasonable changes that you could recommend. 

2.  Use the 5As of Obesity to help start a conversation when you note that your patient carries excess weight. 

3.  Focus on small steps - use the tool for suggestions. 

4.  Don't do it alone (if possible) - nutrition counselling and weight management require multidisciplinary support!  Engage any support you have to help provide your patient the help they need from various avenues: dietitian, nutritionist, psychologist, health/weight management classes - anything you can find to provide your patient with lots of health care provider time to guide them through their journey. 


Follow me on twitter! @drsuepedersen

www.drsue.ca © 2018

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Are Less People With Overweight Or Obesity Trying To Lose Weight?

>> Saturday, January 6, 2018



As we look forward into a new year, it is also worthwhile to cast a glance backwards in time to understand how perceptions and attitudes towards weight loss may be changing, in the face of a landscape where obesity is on the rise.

One of the most read 2017 studies in the Journal of the American Medical Association used the American National Health And Nutritional Examination Survey (NHANES) data to assess whether there has been any change in the percentage of people with overweight or obesity (defined as BMI of 25 or greater) trying to lose weight during the time frames of 1988-1994, 1999-2004, and 2009-2014.

Upon analysis of the data from 27,350 people aged 20-59, they found that the percentage of people with overweight or obesity increased over time, from 52.7% in 1988-1994, to 65.6% in 2009-2014.

The percentage of people trying to lose weight decreased during the same period, from 55.7% in 1988-1994, to 49.2% in 2009-2014.

So why would the proportion of people trying to lose weight be decreasing, while obesity is actually on the rise? 

Well, we know that there has been a generational shift in perceptions of body weight norms - in other words, people with overweight are less likely to classify themselves as such as they did in years past, because overweight may be perceived more like the 'new normal'.  So if people who carry excess weight perceive themselves to be of a healthy weight, they would be less inclined to try to lose weight.

The authors of this study suggest that the length of time that people struggle with obesity may be a factor - the longer people live with obesity, the more frustrated they may be come with unsuccessful weight loss attempts and thus less likely to try to manage their weight.

I think the issues go even deeper - and likely have much to do with barriers to effective obesity care that we know exist.  The ACTION study in USA highlighted some of these important barriers that needed to be addressed.  Data collection for the ACTION study in Canada (for which I am an author and member of the Steering Committee) is now complete; we are currently working hard to put together and publish our results, to better understand barriers that exist, and how we as a country can overcome these barriers to better help Canadians with weight management.   


Follow me on twitter! @drsuepedersen

www.drsue.ca © 2018

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