The Bugs In Your Gut - Could They Cause Obesity or Diabetes?

Did you know that you have more bacterial cells inside your intestines than you have human cells in your entire body?  Not only that, but they house somewhere between 250 to 800 times more genes than we have human genes in our body.   Perhaps it's not so far out, then, for us to learn that these bacteria (called the 'microbiome') play an important role in our metabolism, and are very likely to contribute to the risk of both obesity and type 2 diabetes.

A wonderful Viewpoint article in JAMA (free to read online here) outlines what we know about this topic so far.

The microbiome has many important functions, including the production of important amino acids (protein building blocks) and vitamins, and they also help to degrade toxins.  The genes in these bacteria also produce hormones and inflammatory molecules that enter our circulation and effect our health.

These bacteria also play a role in how many calories we absorb from food, because they make enzymes that help us to digest polysaccharides, a type of carbohydrate.  Some types of gut bacteria are better at this than others, and studies have shown that people with obesity carry more of the carb-digesting bacteria (called Firmicutes) than people without obesity.  Interestingly, some studies have shown that when a person with obesity loses weight, particularly after bariatric surgery, the proportion of 'good' bacteria (called Bacterioides) increases relative to the 'bad' Firmicutes. Overall, the studies suggest that the gut bacteria may be both a cause and a consequence of obesity.

Along with the increased capacity to absorb carbs in people who carry more Firmicutes bacteria, so comes an increased risk of having not only obesity, but also type 2 diabetes.  Altered production of short chain fatty acids by gut bacteria, as well as low grade gut inflammation caused by chemicals made by the microbiome, also contribute to insulin resistance and diabetes risk.

So how does this play out in terms of treatment of obesity or diabetes? Well, some studies (mostly done in rodents, but some in humans too) have shown that manipulation of the gut microbiome by way of stool transplants (yep, transplanting poo), or perhaps by other modalities such as change in diet or probiotics, may be able to have an effect on the type of bacteria we have, but we are far from developing concrete treatment approaches.   However, as we learn more about our gut bugs and the genes they carry, we come steps closer to learning how we may ultimately be able to incorporate microbiome modification into our treatment options for obesity and metabolic syndrome.

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New Canadian Diabetes Association Clinical Practice Guidelines Update

While the full Canadian Diabetes Association (CDA) Clinical Practice Guidelines are formally updated every 5 years (with the next edition due in 2018), interim updates are published if new evidence emerges that is considered to be practice changing.  As such, the CDA has just released an interim update with revised recommendations, in light of the new cardiovascular outcome trial of a diabetes medication called liraglutide.

As blogged previously, in people with type 2 diabetes who were at high risk of cardiovascular disease, the liraglutide cardiovascular trial (called the LEADER trial) demonstrated that liraglutide reduced the risk of cardiovascular events by 13%.  Put another way: if 66 people are treated for 3 years with liraglutide, one cardiovascular event would be prevented.

In the LEADER trial, 81% of patients had a past history of established cardiovascular disease, while 19% of patients did not (but they were still considered to be at high risk of CV events due to their risk factors).  Subgroup analyses suggested that it was patients who had a history of established cardiovascular disease who had the reduction in risk with liraglutide. As patients had to be age 50 or older to be included in the study, we do not know if these findings apply to a younger population.

In the revised CDA Guidelines, liraglutide now joins another medication called empagliflozin, as medications to consider after metformin, in patients with type 2 diabetes and established cardiovascular disease, who are not at target blood sugar control.  As ongoing cardiovascular outcome trials of diabetes medications are completed and published, the CDA Guidelines will be updated accordingly.

I have pasted the new algorithm below, but the resolution isn't great - it's a little friendlier on the eyes here.

Disclaimer: I am a member of the Expert Committee for the writing of the Canadian Diabetes Association 2018 Clinical Practice Guidelines. 

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Reality Check on Coconut Oil

In today's marketplace, it seems that we are constantly being presented with the next great thing - a way of eating, a food product, or a supplement, promising health benefits ranging from better skin to weight loss to a longer, healthier life.   Because marketers are so slick, it is often really tough to figure out which claims are true, and which are an inflated or completely false version of reality.

Coconut oil is an example of a very successful marketing engine that has tirelessly promoted the its benefits, to the point where it seems almost commonly accepted that coconut oil is a healthy choice.

Coconut oil is an oil that is extracted from the nut of the coconut palm tree.  Coconut oil is actually one of the least healthy oils you can eat, because it is almost purely saturated fat - it contains even more saturated fat than lard.   Overall, studies show that saturated fat consumption is associated with an increased risk of heart disease.


(Sidebar: While studies overall have suggested that saturated fat is associated with an increased risk of heart disease, this has recently come into question with recovery of data from Minnesota Coronary Experiment in the 1960s.   What is quite clear (from much more recent studies) is that replacing saturated fat with carbohydrates (ie a low fat, high carb diet) does not reduce heart risk.  In fact, eating excess carbs as a replacement for saturated fat actually increases the risk of diabetes, weight gain and metabolic syndrome. Conversely, replacing saturated fat with polyunsaturated fat in your diet can confer substantial health benefits, possibly including a reduction in cardiovascular events and mortality - read recent studies about this here and here.)



So why has coconut oil been touted as a 'healthy' fat?  Here are some of the health claims that have been made:


1. Health Claim: Medium chain fatty acids (contained in coconut oil) may not raise bad cholesterol (LDL) as much as long chain fatty acids (found in other oils) do.

Reality check:  This is highly controversial, with conflicting results in the small studies that have been done.  There is also very little study of the effect of coconut oil on heart health, which is why we we care about LDL in the first place.  Contrast this with extra virgin olive oil, which has been shown as part of a randomized clinical trial to reduce the risk of cardiovascular disease.


2.  Health Claim: Fatty acids in coconut oil (medium chain) may not be as readily stored in fat tissue as long chain fatty acids.

Reality check: Whether or not this is true, adding additional fat to your diet should be avoided - coconut oil still contains 117 calories per tablespoon (this is about 10% of the total calories for a whole day for a typical woman trying to lose weight).


3.  Health Claim: Coconut oil can improve Alzheimer's disease and/or dementia.

Reality check:  This claim started with a YouTube clip that went viral in 2012, showing a patient with Alzheimer's who dramatically improved with eating coconut oil.  This case was never confirmed or reported in any medical or scientific literature, and there is no clinical trial data to substantiate or refute this claim.


THE BOTTOM LINE:   Avoid adding extra fat to your diet.  When you do use fats or oils for cooking, monounsaturated or polyunsaturated fats are a better choice than saturated fat (eg extra virgin olive oil and canola oil).  Coconut oil is not the way to go.

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Risks of Overweight and Underweight Before Pregnancy

Doing one's best to achieve an appropriate amount of weight gain in pregnancy is important for best health outcomes for baby and mother.  As it turns out, mom's weight before pregnancy is an important predictor of birth outcomes as well.

A recent review summarizes available data on this issue, looking at 60 studies involving over 1.3 million women.

They found that for women with overweight or obesity before pregnancy, compared to women with normal weight, the risks were as follows:

• 45% higher risk of having a large for gestational age baby
• 24% higher risk of having a small for gestational age baby
• 29% higher risk of the newborn baby needing admission to intensive care after birth
• 27% higher risk of stillbirth

For women with underweight before pregnancy: (again, compared to women with normal weight)

• 30% higher risk of preterm birth
• 67% higher risk of having a small for gestational age baby

These data remind us of the importance of managing weight as well as possible not only during pregnancy, but also before consideration of pregnancy. 

Recommended weight gain during pregnancy is based on pre-pregnancy Body Mass Index, and can be calculated using Health Canada's handy Pregnancy Weight Gain Calculator. 

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Could Diet Drinks Be Sabotaging Your Weight Loss Efforts?

We know that consumption of beverages containing sugar increases the risk of obesity, metabolic syndrome, and type 2 diabetes, so it is often advised to consume diet drinks instead.  However, it has been suggested that even diet beverages may be associated with an increased risk of type 2 diabetes.  As such, a recent study studied the effect of diet beverages vs water as part of a weight management program in women with overweight or obesity and type 2 diabetes.

The study, published in Diabetes, Obesity & Metabolism, randomized 81 women who were habitual consumers of diet beverages, to consume either water after lunch five times per week instead of her usual diet drink, or to continue to drink diet beverages after lunch, during a 6 month weight loss program which consisted of dietary modifications and exercise.

They found that women who switched up diet drinks to water had a 1.2kg greater decrease in body weight compared to women who continued to drink diet beverages, as well as greater improvements in fasting blood sugar, fasting insulin levels, and post meal blood sugars.

While the differences in the study were small, it is interesting to consider how diet drinks could be detrimental to weight loss efforts.  It has been proposed that artificial sweeteners may raise the hedonic desire for sweet, energy dense foods. The women drinking diet beverages did consume a few more calories per day than those drinking water, so this may be a plausible mechanism of the differences seen in this study.  There may also be an effect of sweeteners on gut bacteria, which we are learning have an important impact on energy balance and metabolic homeostasis.

It should also be noted that there is conflict in the research in this area, with other studies showing no effect on weight between water vs diet beverages or even a benefit of diet beverages over water.

However, based on the current study, it seems that water may be best.

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Do Calcium Supplements Increase The Risk Of Heart Disease?

Calcium is a nutrient that is essential for bone health.  While adequate calcium intake is recommended for maintaining bone health, some studies have suggested that calcium supplements may increase the risk of heart attack.  It seems that these fears may not have been warranted after all: the most recent review of existing literature suggests that recommended levels of calcium intake are NOT associated with cardiovascular risk in generally healthy adults.

The data on calcium supplements and heart disease risk was recently assessed in systematic review and meta-analysis done by the American National Osteoporosis Foundation, and published as a joint position statement with the American Society for Preventive Cardiology.  Published in the Annals of Internal Medicine, they found that calcium intake from either food or supplement sources at levels within the recommended tolerable upper intake range in USA of 2000-2500 mg/day are not associated with cardiovascular disease risk in generally healthy adults.

They do recommend that wherever possible, recommended intake of calcium should be obtained through natural food sources rather than supplements, but that supplements can be used safely when food sources do not meet goals.  One of the theories behind the benefits of getting calcium through real food is that absorption of calcium occurs more gradually from the intestinal tract, whereas absorption of calcium from supplements may be faster, resulting in more of a ‘spike’ of calcium in the blood.

The authors note that the available data to answer this question about calcium supplements and cardiovascular health is not the best, as none of the studies looked at cardiovascular endpoints are the primary outcome.  This type of study is unlikely ever to be done, as it would be very costly and likely need to be very large to detect small differences.  In the absence of such data, the currently available data suggests that calcium supplements are a safe approach to reach recommended calcium intake, in situations where calcium intake from real food is insufficient.

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Pregnancy After Bariatric Surgery - How Long Should You Wait?

After bariatric surgery, it is recommended to wait at least 12-18 months (with some guidelines recommending to wait two full years) before considering pregnancy.  This is because rapid weight loss and a higher risk for nutritional deficiencies occurs during this phase, which may be a poor environment for fetal development. However, a recent study suggests that waiting two years may not be enough.

The study, published in JAMA Surgery, looked at data from women and their infants in Washington state who had had bariatric surgery (n=1859), and compared them to women and their infants who had not had bariatric surgery (n=8437).  They found that babies who were born to mothers who had had bariatric surgery had a 57% higher risk of prematurity, 25% higher risk of needing to be admitted to the NICU, 93% higher risk of being small for gestational age.

However, when 4 years or more had elapsed since bariatric surgery, the risk of these outcomes was lower when compared to women where 2 years or less had elapsed.  Specifically, the risk for babies born less than 2 years after bariatric surgery was 48% higher for prematurity and 54% higher for NICU admission, compared to babies born to mothers where 4 years or more had elapsed (the difference for being small for gestational age was not significant). For babies born in the 2-4 year window after bariatric surgery, the authors note that the prevalence of prematurity and NICU admission was not meaningfully different from babies born to women who had not had bariatric surgery.

So how do we interpret these data? Well, we already knew that the risks identified in this study exist for babies born to mothers after bariatric surgery, but we need to remember that there are benefits to pregnancy outcomes after bariatric surgery as well - for example, less babies born large for gestational age, less labor and delivery complications, lower risk of C section birth, lower risk of gestational diabetes and high blood pressure in pregnancy.  However, based on these data, it may be better to wait even longer than two years after bariatric surgery before conceiving.

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Poke Free Blood Sugar Monitor Helps Prevent Lows

On behalf of my patients who struggle with the discomfort of having to poke their fingers to check their blood sugars every day, I am super excited about a new poke-free technology that will hopefully be approved in Canada soon – the Freestyle Libre.  With this glucose monitoring system, a small patch is applied to the upper arm with a tiny filament underneath which inserts under the skin.  Wave your glucose monitor over the patch and voilà! – the last 8 hours of blood sugars, including current blood sugar, are transmitted to your monitor for evaluation.  Not only that, but it tells you the current trend in sugar (ie if your blood sugar is on its way up, down, or stable).

In the first randomized controlled trial of this device, it has now been show that monitoring with the Libre helps patients with type 1 diabetes prevent hypoglycemia (low blood sugars).  The study, published in The Lancet, randomized 241 patients with good blood sugar control to the Libre vs usual monitoring with finger pokes.  They found that over 6 months, people using the Libre spent 38% less time with low blood sugars than people using standard finger pokes.  (Despite this benefit, people using the Libre still spent a shocking 2 hours per day with low blood sugar, compared to 3.3 hours per day for people taking finger pokes - so clearly a better monitoring approach is only part of the solution.)

Ten patients reported concerns related to the sensor, primarily itching, allergic reaction, or redness at the site (not out of keeping of the usual risk of reactions to medical devices that stick to the skin).  Some aspects of quality of life were reported to be improved as well – not surprising,  since studies have shown that people with diabetes who have had severe low blood sugar in the past fear this occurring again as much as they fear blindness as a complication of their diabetes.

It would be interesting for this study to be repeated in people with type 2 diabetes, and also to compare the Libre to the continuous glucose monitoring system.

Bottom Line: The Libre would be a strong addition to our blood glucose monitoring options for diabetes in Canada.

Disclaimer: I have received honoraria as a continuing medical education speaker and consultant from the makers of the Freestyle Libre (Abbott). 

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www.drsue.ca © 2016

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Want A Lower Calorie Meal To Go?

For those days when you know you're going to need to eat on the run, it can be especially hard to resist the temptations of the take-out restaurant or deli that you hit up for your lunch.  A great way to cut calories on those days was proven in a recent study - order well ahead!

The study, published in the Journal of Marketing Research, found that longer delays between placing a lunch order and eating lunch was associated with a reduction in calorie content of the order, with 38 calories less ordered per hour of delay between the order and lunchtime.  They also found that people who ordered lunch immediately before eating had the highest calorie content of their order - about 100 calories more than someone ordering earlier in the day.

Ordering lunch soon after breakfast may be the best time to order, perhaps because of fullness from breakfast, or perhaps because it's easier to think about exerting self control over our future selves than our present selves.  Perhaps the stress of the day hasn't yet taken hold in the earlier morning, allowing us to make healthier lunch choices (stress can cause us to eat more and crave unhealthy foods).  Whatever the reason, try ordering lunch when you get to the office in the morning, and let me know how it goes via comments to this post!

Thanks to my friend Bob for the heads' up on this study!

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Type 2 Diabetes Medications Exenatide Weekly and Dapagliflozin Studied In Combination

In the wake of the recent annual European diabetes (EASD) meeting, another important study (and heavy science blog post!) coming your way today.

In the care of people with type 2 diabetes, we have fully 9 classes of glucose lowering medications to choose from in Canada.  While some of these medications can cause weight gain, others are weight neutral, and some can cause weight loss, in addition to improving blood sugar control.  Two classes of medications can cause weight loss, namely the GLP1 receptor agonists, and the SGLT2 inhibitors.  As 90% of people with type 2 diabetes also have overweight or obesity, it is of interest to know whether these two classes of medications can be used together, for even better blood sugar control and greater weight loss.

Two of these medications, the GLP1 receptor agonist exenatide qweekly (Bydureon) and the SGLT2 inhibitor dapagliflozin (Forxiga) have now been studied in combination.  Recently published in The Lancet Diabetes & Endocrinology, the study randomized 695 patients with a baseline hemoglobin A1C of 8-12% to receive either exenatide qweekly, dapagliflozin, or the two medications in combination. 

After 28 weeks, hemoglobin A1C decreased by 1.6% in the exenatide group, by 1.4% in the dapagliflozin group, and by 2.0% in the combination group.   While the medications together were better than either drug alone, the benefit was not additive.  This does not surprise us, as we know that the higher starting A1C, the greater reduction we will see – so to be on two medications together would not expect to give an additive result compared to either medication alone.

The weight loss seen was additive, with a loss of -1.54kg in the exenatide group, -2.19kg in the dapagliflozin group, and -3.41kg in the combination group. Blood pressure reduction also exhibited an additive response, with a systolic BP reduction of -1.3mmHg on exenatide, -1.8mmHg reduction on dapagliflozin, and a full -4.2mmHg reduction on the combination.  These additive benefits make sense, given that each of these medications has a different mechanism of action on weight and blood pressure.

From a safety point of view, side effects that were seen were as expected from what we already know about each of these classes of medications, with no suggestion for any negative side effects of using the two medications in combination.

Finally, we have much awaited data that shows us that these two medications can be used safely in combination, with the result of better diabetes control, and an additive effect on both weight loss and blood pressure.

Disclaimer: I am involved in research trials of GLP-1 receptor agonists and SGLT2 inhibitors.  I receive honoraria as a continuing medical education speaker and consultant from the makers of exenatide and dapagliflozin (Astra Zeneca). 

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Diabetes Medication Semaglutide Decreases Cardiovascular Events

Hot off the presses from the New England Journal of Medicine – an emerging type 2 diabetes medication called semaglutide has been shown to decrease cardiovascular events in a high risk population with type 2 diabetes.

The two year study, called the SUSTAIN-6 study and in which I was an investigator, enrolled 3,297 people from 20 countries around the world who had established cardiovascular disease, or at least one cardiovascular risk factor.   They were randomized to receive either semaglutide 0.5mg, semaglutide 1.0mg, or placebo as once weekly subcutaneous injections.

The primary outcome of the study, which was a composite outcome of first occurrence of nonfatal heart attack, nonfatal stroke, or cardiovascular death, was found to be reduced by 26% compared to placebo, with 6.6% of patients on semaglutide experiencing an event, vs 8.9% of patients on placebo.   When we look at these endpoints individually, there was a significant reduction of 39% of nonfatal stroke, whereas the differences in nonfatal heart attack and death were not significant.  

Although all patients in the study were treated to achieve target glycemic control, blood glucose control was better in the semaglutide groups, with hemoglobin A1C reduced by 0.7% and 1.0% in the semaglutide 0.5mg and 1.0mg groups respectively, compared to placebo, despite the fact that insulin needed to be started twice as often in the placebo group than in the semaglutide group.

In terms of other complications that we are aiming to prevent in people with diabetes, rates of new or worsening kidney disease was reduced with semaglutide.  The risk of retinopathic (eye) complications was higher, experienced by 3% of patients on semaglutide vs 1.8% of patients on placebo.  Rarely, achieving glycemic control rapidly (particularly when sugars start off very high) can paradoxically increase the risk of eye complications.  It is not clear if this was the reason in these patients; a direct effect of semaglutide cannot be ruled out.

So what does this mean for the care of people with type 2 diabetes?  The above results suggest that 45 people with type 2 diabetes and high cardiovascular risk would need to be treated for 2 years in order to prevent one cardiovascular event.  In the diabetes world, this is an impressive benefit, similar to the benefit of statins for cholesterol, and also in a similar realm to the two other diabetes medications, empagliflozin and liraglutide, that have been shown to prevent cardiovascular events (read more here and here).  The data showing cardiovascular benefit on all three of these medications has come out within the last year – before that, we did not have definitive evidence that any diabetes medication clearly reduces the risk of cardiovascular events.

It is indeed wonderful that we now know that some glucose lowering medications are able to prevent cardiovascular events in people with type 2 diabetes.  While semaglutide has not yet been approved for use, this study suggests that it will be a beneficial addition to our type 2 diabetes treatment armamentarium.

Disclaimer: I have been involved in research trials of semaglutide, other GLP-1 receptor agonists including liraglutide, and SGLT2 inhibitors like empagliflozin.  I receive honoraria as a continuing medical education speaker and consultant from the makers of semaglutide and liraglutide (Novo Nordisk) and empagliflozin (Boehringer-Ingelheim/Eli Lilly).  

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Barrier to Exercise - Low Sugars in Diabetes

A healthy lifestyle includes exercise, and is part of standard recommendations to most people for maintenance of health and well being.  People with diabetes who take medications that can cause low blood sugar usually have to alter medications and/or food intake to avoid having a low blood sugar induced by the exercise.  A low blood sugar can be a very frightening experience -  sadly, as a recent study shows, the fear of having low blood sugars may actually prevent people with type 1 diabetes from engaging in exercise.

The study, published in the Canadian Journal of Diabetes, surveyed over 500 adults with type 1 diabetes, asking about how they manage their diabetes in the context of exercise.

The majority of these people said that they increased carbohydrate intake before (79%) and after (66%) exercise, and about half of them decreased their meal time insulin before and/or after exercise.  Despite making these adjustments, however, 70% of people reported that they still experience low blood sugars after exercise.  Fear of low blood sugars was identified as a barrier to exercise.

While people with type 2 diabetes were not surveyed in this study, I can attest to the fact that people with type 2 diabetes who are taking medications that can cause low blood sugars (insulin, sulfonylureas, and meglitinides) share these concerns and struggles in preventing low sugars with exercise.

Newer insulins are becoming available to decrease the risk of low blood sugars, and much work is being done to advance the technology in glucose sensing and insulin pump devices as well. For people with type 2 diabetes, medications that do not cause low blood sugar may be an option.    But for those who do take insulin or medications that can cause low sugars, the most important part of avoiding lows around exercise as much as possible is working closely with your diabetes educator to find strategies that work for you.  Each person will be different in terms of what medication they are taking; what kind of exercise is being done and for how long; eating patterns; and how your body responds to that particular exercise.  If you have diabetes and are struggling with preventing lows around exercise, be sure to see your diabetes educator to explore strategies that will work better for you.

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Duodenal Mucosal Resurfacing for Treatment of Type 2 Diabetes?

Our knowledge and understanding about the role of gut hormones in type 2 diabetes continues to grow, as we get a better understanding of the mechanisms involved in the often dramatic improvement in diabetes that is seen after bariatric surgery.  In gastric bypass surgery, we know that at least one of the mechanisms involved is food literally bypassing the first segment of the small intestine, called the duodenum.  This effect may be seen because food is more rapidly delivered to the intestine further down, causing a more powerful release of hormones from the more distal intestine (called the hindgut hypothesis).  However, there may also be an as yet unidentified hormone (or hormones) secreted by the first part of the gut that have an antidiabetic effect, and by having food skip over this part of the gut, this mystery antidiabetic hormone is not released, thereby improving blood sugar control (called the foregut hypothesis).  We do know that the surface of the duodenum in a person with diabetes is altered, with a sort of overgrowth of cells in the duodenal mucosal (called hypertrophy and hyperplasia).

For believers of the foregut hypothesis, a novel approach called Duodenal Mucosal Resurfacing (DMR) is now being studied to see if diabetes control can be improved by doing a sort of 'thinning out' of the lining of the upper part of the intestine.

The first human study of DMR, recently published in the journal Diabetes Care, performed the DMR procedure in 39 patients with type 2 diabetes.  They found an improvement in diabetes control at 6 months post procedure, with greater improvement in those who had a longer segment of the duodenum ablated than those that had a shorter segment treated. Improvement in blood sugars was seen as soon as 1-2 weeks after the procedure, despite no restrictions in diet or calorie intake being recommended.  The improvement in diabetes control was not as powerful as what is seen with gastric bypass surgery, suggesting that there are many additional elements at work in gastric bypass surgery.  The authors also noted that there was some erosion of the improvement in diabetes control at 6 months, so certainly larger and longer studies need to be done to understand what the effect of this procedure is over the long term. There was little weight loss in this study (only a few kg), so the DMR does not hold promise as a weight management strategy.   The procedure was well tolerated overall, though there were three cases of duodenal stenosis that were treated with balloon dilatation.  The authors noted no signals for malabsorption (eg no calcium abnormalities or iron deficiency anemia), but this would need to be evaluated carefully in long term studies as well.

It will be interesting to see further study of the DMR procedure.

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Do Electric Assist Bikes Count As Exercise?

While highly frowned upon when snuck into the Tour de France (are you kidding me?!), electric bikes can be a very useful piece of equipment to zip around town.  These are bicycles that are equipped with electrical assistance, which is activated only when the rider is actively pedalling.  You may wonder – does using these bikes still count as exercise?  A recent study tells us – yes!

The study, published in the European Journal of Applied Physiology, enrolled 20 people who led sedentary lifestyles, and evaluated several measures of health after 4 weeks of using the electrically assisted bike for at least 40 minutes, three days per week. 

They found that using the ‘pedelec’ bikes provided a moderate level of exertion, similar to walking (4.9 METs on average).  After just 4 weeks, there was an improvement in their glucose tolerance, and an increase in their power output and VO2max (a measure of maximal aerobic capacity).    Participants also found the bikes to be fun, to the point where over half of participants ended up cycling over 50% more than the required amount.

So, while using a regular bicycle would provide more exercise, a pedelec bike is a great option for people who have knee problems, struggle to get uphill on a bike, or if you want to get further in a day than you otherwise would on a regular bike.  (We used them on a trip Kyoto last year so we could make it to all the far flung temples we wanted to see – fantastic!)    Pedelecs remove the potential deterrents of cycling such as longer distances or hills, and they can be incorporated into daily life as a means of transport when the weather/climate permits (rather than having to find specific extra time in the day to exercise).  

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Does Losing Weight Improve Fertility in Polycystic Ovary Syndrome?

Polycystic ovary syndrome (PCOS) is a very common cause of infertility.  Women with PCOS often have infrequent periods, decreased or absent ovulation, and can also have unwanted hair growth (eg to face or abdomen) and/or acne.  The underlying problem is that of insulin resistance, which (long story short) causes the ovaries to overproduce testosterone.  While about half of women with PCOS have a normal and appropriate body weight, the other half have overweight or obesity; also, we know that PCOS gets worse with weight gain and better with weight loss (in those who carry excess weight).

So, a natural question to ask is whether weight loss could improve fertility in women with PCOS and overweight or obesity.

A study was recently published to answer this question.  In the study, which was a post hoc analysis of two concurrently run randomized clinical trials, four approaches were compared in women with PCOS, infertility, and overweight or obesity:

• immediate treatment with clomiphene
• birth control pill for 4 months followed by clomiphene
• lifestyle treatment and antiobesity medication for weight loss for 4 months, followed by clomiphene
• birth control pill and lifestyle treatment and antiobesity medication for weight loss for 4 months, followed by clomiphene

They found that women who were treated with clomiphene without weight loss treatment had an ovulation rate of 45%, and a birth rate of 10.2%.  These numbers were nearly identical in the women who were on the birth control pill for 4 months before getting clomiphene.

In contrast, women who had lifestyle/antiobesity medication (with or without the birth control pill) had a higher rate of ovulation (63%) and a higher birth rate of 25%.  They lost an average of 6.5% body weight in the four month treatment period before receiving clomiphene.

For a woman with PCOS and infertility who carries excess body weight, these finding could present a dilemma: does one go ahead with fertility treatment and hope for the best, or is it better to try to lose weight first, before embarking on fertility treatments?  Women are more likely to start thinking about getting pregnant well into their 30s in this day and age, so there may be a palpable time pressure against taking the time to try to lose weight first.  An important point to consider is that not only does weight loss improve fertility (as per this trial), but it also decreases the risk of the future child developing obesity and type 2 diabetes.  In addition, going into pregnancy with a healthier weight and carrying a healthier weight in pregnancy also decreases the risk of many complications of pregnancy, including gestational diabetes, pregnancy induced hypertension, and babies born large for gestational age (which carries a host of risks and potential complications).

Finally - a note that antiobesity medications must be stopped before attempts to become pregnant, as there is no safety data on these medications in conception/pregnancy.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2016

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Does Exercise Improve Fatty Liver Disease?

Nonalcoholic fatty liver disease is a potential consequence of carrying excess body weight, and is essentially caused by extra fat being stored in the liver. It is the third most common cause of liver cirrhosis, and affects up to 30% of the world’s population. 

Weight loss has been clearly established as the first line treatment for NAFLD, and we know that most successful weight loss strategies focus most attention on reducing calorie intake, with exercise playing only a minor part.  However, we know that exercise can have many cardiometabolic benefits even if a person doesn’t lose weight because of it, so it would be interesting to know if exercise itself could improve NAFLD.

A study was recently published in JAMA Internal Medicine which addresses this question.  In the study, 220 participants with NAFLD were randomly assigned to moderate exercise (brisk walking for 30 mins, 5 days per week) for a year, vigorous exercise for 6 months followed by moderate exercise for 6 months, or no additional exercise for a year.

They found that moderate and vigorous exercise were equally effective to reduce fat content in the liver, and that most (but not all) of the effect was mediated by weight loss. 

So, while actual reduction in weight remains the key factor in improving fatty liver, exercise may play some role even if the exercise itself doesn’t shed a whole bunch of pounds.  And it is good news that moderate activity is just as good as intense activity, as moderate exercise regimens like walking are more likely to be adhered to in the long run.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2016

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(In)Accuracy of Your Wrist Technology for Estimating Calorie Burn

There are many different kinds of wrist technology out there - Garmin, FitBit, and Jawbone UP just to name a few.   In response to concerns that these devices may not be accurate to measure energy burn, researchers have now conducted a study to test how accurate they are.


The study, published in JAMA Internal Medicine, examined several brands of wearable energy tracking technology, and compared them to gold standard research methods of measuring energy burn, including both a standardized day (indirect calorimetry using metabolic chamber) and fifteen free living days (doubly labeled water method).  Brands studied included the Garmin VivoFit, Jawbone UP24, and FitBit Flex.

They found that these wearable devices were overall quite inaccurate, with inaccuracies ranging as high as 590 calories per day. !  Most of the inaccuracies were underestimates of caloric needs, while some overestimated needs.

So does this mean that these devices are totally useless?  No.  They can be great motivation for keeping track of daily activity and steps taken per day (pedometer) - though there are inaccuracies here as well.  But I do see a lot of people with weight struggles feeling frustrated that they seem to be burning way more calories (according to their device) than the food they are eating, yet they are not losing weight.   Overall, the biggest benefit of these devices is probably motivation to move, and keeping us engaged in mindful eating (ie we think more about what we are eating if we are keeping track of it).

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2016

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Diabetes Medication Liraglutide Saves Lives

In follow up to my recent blog post – as promised - the hotly anticipated LEADER trial results became available this week, in a simultaneous release at the American Diabetes Association meeting, as well as published in the New England Journal of Medicine.

The LEADER trial examined the effect of a type 2 diabetes medication called liraglutide (trade name Victoza) on cardiovascular events, in a group of people with type 2 diabetes who were deemed to be at high cardiovascular risk (age 50 or more with at least one existing cardiovascular condition such as a history of heart attack or stroke; or age 60 or more with at least one cardiovascular risk factor (for example, hypertension).

The goal of this study, as for all hard outcome studies of diabetes medications, was to prove cardiovascular safety of liraglutide.  

Not only did liraglutide prove to be safe in people at high cardiovascular risk – it actually REDUCED cardiovascular events.  Amongst 9,340 patients from 32 countries, followed for a median of 3.8 years, there was a 13% reduction in the risk of (a composite endpoint of) death from a cardiovascular causes, non fatal heart attack, and non fatal stroke. Cardiovascular deaths were reduced by 22%, and death from any cause was reduced by15% compared to placebo.  The benefit of liraglutide was particularly pronounced in people who had established cardiovascular disease at baseline, and in those with moderate reduction in kidney function at baseline.

To put the results another way:  

• 66 people would need to be treated for 3 years to prevent one of (cardiovascular death or heart attack or stroke)
• 98 people would need to be treated for 3 years to prevent one death of any cause.

These numbers needed to treat are similar to the protective effects of statins (cholesterol medications) and ACE inhibitors (blood pressure medication).

Now that we know that liraglutide has a distinct cardiovascular benefit, a question that arises is whether this is an effect shared by other medications in this class, called GLP-1 receptor agonists.  The ELIXA trial, a study of lixisenatide (not available in Canada), did not show a cardiovascular benefit.  Studies of other medications in this class (eg dulaglutide, exenatide) are still underway, so for these, we don’t know the answer yet.  

We also don't know if the cardiovascular benefit of liraglutide exists in people with type 2 diabetes who aren't in these high risk groups, or in people with obesity without type 2 diabetes (liraglutide is also available as an obesity treatment, called Saxenda).  However, this trial gives us additional confidence in the safety of liraglutide, given that the LEADER trial was conducted in the highest cardiovascular risk population.

The effect of liraglutide to reduce cardiovascular events is important, as we know that cardiovascular disease is the leading cause of death in people with type 2 diabetes.  So far, other diabetes medications that have shown a cardiovascular benefit are metformin (with somewhat scanty data) and empagliflozin (based on the EMPA-REG trial, which you can read about here). Thus, in Canada, metformin is considered the first line treatment for type 2 diabetes, with empagliflozin to be considered in patients with existing cardiovascular disease who are not at target blood sugar control with metformin.  

Liraglutide will likely join the ranks of empagliflozin as a second line treatment option, with the decision making process as to which to choose based not only on the characteristics of each medication, but most importantly, on the characteristics and desires of each individual patient.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2016

Disclaimer: I have been involved in research trials of liraglutide, other GLP-1 receptor agonists, and SGLT2 inhibitors like empagliflozin.  I receive honoraria as a continuing medical education speaker and consultant from the makers of liraglutide (Novo Nordisk) and empagliflozin (Boehringer-Ingelheim/Eli Lilly).  

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