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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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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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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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.

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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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Diabetic Ketoacidosis After Bariatric Surgery in Type 2 Diabetes

Diabetic ketoacidosis (DKA) is a potentially life threatening complication that can occur in people with diabetes.  While we typically associate DKA with type 1 diabetes, it can also rarely happen in type 2 diabetes.   DKA can occur if insulin levels are low, and can be precipitated by a stress on the body, including infection or illness, dehydration, heart attack, and so forth.

A case series was recently published, describing four cases of DKA after bariatric surgery, in three people with type 2 diabetes.   The average time to presentation of DKA was 13 days after surgery (range 3-27 days). All patients were on insulin prior to surgery.  Factors contributing to DKA included omission of insulin and dehydration.

One of these patients was on canagliflozin prior to surgery.  Canagliflozin is a medication in a class of type 2 diabetes medications called SGLT-2 inhibitors, which slightly increase the risk of DKA, particularly if insulin is not taken as directed by the health care team.  Also, if a person taking an SGLT2 inhibitor becomes unwell or dehydrated for any reason while taking the medication, this increases the risk of DKA.  The DKA case in the patient on canagliflozin in this study also had omission of insulin and poor food intake post operatively as contributory factors.

These findings teach us the following:

1.  Patients with type 2 diabetes having bariatric surgery need to be followed closely postoperatively, with meticulous attention to blood sugars and insulin needs.  Some people with type 2 diabetes who were on insulin before surgery do not require insulin after surgery, but others do.   There must also be a low threshold for concern if they become dehydrated due to difficulty tolerating oral intake.

2.  SGLT2 inhibitors should be stopped prior to bariatric surgery (possibly before starting any low calorie diet plan), and if there is still a need for medication to control blood sugar post op, it should not be restarted until the patient is eating and drinking well after discharge home from surgery.

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JDRF Reaches Out To Fort McMurray Evacuees with Type 1 Diabetes

In the wake of the wildfires that have ravaged Fort McMurray, there have been many heartwarming stories of outreach and support to victims of this monumental natural disaster.

The JDRF (formerly known as the Juvenile Diabetes Research Foundation) is reaching out to Fort Mac victims living with type 1 diabetes to help ensure they have ongoing access to insulin, test strips and supplies.  Here is the media release directly from the JDRF:

Media Advisory

JDRF Canada Assisting Fort McMurray Individuals Living with Type 1 Diabetes

The North Central Alberta & Northwest Territories Chapter of JDRF Canada is coordinating with local type 1 diabetes (T1D) support groups to provide assistance for T1D families evacuated from Fort McMurray with their insulin related needs.

Families who were forced to evacuate may have limited access to insulin, test strips and other related supplies. Local social media groups for people living with T1D have been very active with families offering to share their supplies with families in need. “Many people are now in the Edmonton Area while others are in camps around Fort McMurray”, said Dorothy Ross, Regional Director for JDRF in Western Canada “We are compiling the lists of people that are in need with people who can share some of their supply, both in the Fort McMurray area and in other communities in the region.”

People who are either in need of or able to offer supplies can contact JDRF at1-855-428-0343 or local at 780-428-0343. For after hours support, please e-mail Edmonton@jdrf.ca. JDRF staff will coordinate resources with those in need.

About JDRF

JDRF is the leading global organization funding type 1 diabetes (T1D) research. JDRF’s goal is to progressively remove the impact of T1D from people’s lives until we achieve a world without T1D. JDRF collaborates with a wide spectrum of partners and is the only organization with the scientific resources, regulatory influence, and a working plan to better treat, prevent, and eventually cure T1D. As the largest charitable supporter of T1D research, JDRF is currently sponsoring $530 million in scientific research in 17 countries. For more information, please visit JDRF.ca.

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Type 2 Diabetes Medication Semaglutide Reduces Cardiac Risk

Great news from the diabetes world: semaglutide, a medication in development for the treatment of type 2 diabetes and obesity, has been shown to reduce the risk of cardiovascular events.

The SUSTAIN-6 study (a study in which I was an investigator) was a global study of about 3,300 people with type 2 diabetes, who were randomized to receive semaglutide subcutaneously (injected under the skin) once weekly vs placebo for treatment of their diabetes. They found that after 2 years of treatment, semaglutide reduced cardiovascular events (defined as a sum of non fatal heart attack, non fatal stroke, and cardiovascular death).  Exactly how much the risk is reduced is not yet public knowledge - the information is currently available in a press release only, with the exact data to be released at a later date.

Semaglutide is a GLP-1 receptor agonist, which helps the pancreas control the release of hormones involved in blood sugar control (insulin and glucagon), and also stimulates the fullness centre in the brain to tell a person that they feel full.  Thus, not only does it help with blood sugar control, it is also effective for weight loss.  Semaglutide is currently in development as both a type 2 diabetes treatment and as a treatment for obesity in people with or without diabetes (it is not yet available as a prescription).   Interestingly, while all GLP-1 receptor agonists currently available are administered by injection under the skin (similar to how insulin is administered), semaglutide is also currently under development as an oral medication. (ie as a pill)

This marks the third time in the last eight months that we have been so thrilled to hear that a medication designed for the treat type 2 diabetes decreases the risk of cardiovascular events: empagliflozin (trade name Jardiance) (read here) and liraglutide (trade name Victoza) (read here) reduce cardiovascular events as well.  These are landmark times for the world of type 2 diabetes, as prior to these studies, we had not definitively proven that a medication for treatment of type 2 diabetes could decrease the risk of cardiovascular events.  In fact, we have had great difficulty proving that improving blood sugar control by any means reduces cardiovascular events (though it is clear that improving blood sugar control reduces the eye and kidney complications of diabetes).

Amongst the class of GLP-1 receptor agonists, both liraglutide and semaglutide have shown that they reduce cardiovascular events (though the numbers on this are not yet available on either one), whereas lixisenatide (not available in Canada) did not decrease cardiovascular events.  It remains to be seen what effect the other GLP-1 receptor agonists available in Canada have on cardiovascular events (exenatide (trade names Bydureon and Byetta) and dulaglutide (trade name Trulicity)) - these studies are still underway.


Disclaimer: I am involved in research trials of semaglutide for type 2 diabetes and obesity.  I receive honoraria as a continuing medical education speaker and consultant from the makers of liraglutide (Novo Nordisk). 

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Bariatric Surgery For Type 1 Diabetes?

In parallel with the obesity epidemic in our general society, so too do many type 1 diabetics struggle with excess weight.  I am often asked whether patients with type 1 diabetes could benefit from bariatric surgery.

First, a review on the difference between Type 1 vs Type 2 diabetes:

• Type 1 diabetes is an autoimmune condition, where the immune system mounts a response against the pancreas, causing the pancreas to stop producing insulin.  Type 1 diabetics require insulin as treatment.
• Type 2 diabetes is a condition where the body is resistant to the effects of insulin.  This means that the pancreas has to work harder to make enough insulin to put sugar into cells for use as energy.  Over time, the overworked pancreas gets tired, its ability to produce enough insulin to control blood sugars declines, and diabetes develops. Some Type 2 diabetics are treated with lifestyle modification alone, some with pills or injectable medication, and some require insulin because their pancreas is too tired to make the insulin they need.

About 10% of diabetics have type 1 diabetes, and 90% have type 2 diabetes.  Traditionally, we used to think of type 1 diabetes being the kind of diabetes that has onset in thin kids or young adults, and type 2 diabetes as having onset in people with obesity later in life.  It turns out that type 2 diabetes can come on in childhood (the youngest type 2 diabetic recorded in Canada was 5 years old at diagnosis), and type 1 diabetes can sometimes have onset later in life.  Some people with type 2 diabetes have an ideal body weight, and some people with type 1 diabetes struggle with obesity.

There is lots of evidence to support the efficacy of bariatric surgery (especially gastric bypass surgery and sleeve gastrectomy) to improve control of type 2 diabetes, or even send it into remission (meaning the type 2 diabetes goes away - though it may reoccur later).

For type 1 diabetes, there is very little data.  However, a recent review summarizes the literature available for us, and what it found is that while bariatric surgery can be of benefit to help people with type 1 diabetes lose weight and reduce risk factors for heart disease, diabetes control does not seem to improve overall.

So, while bariatric surgery can be an appropriate treatment strategy for type 2 diabetes in people who struggle with obesity, the evidence does not support it for the improvement of diabetes control in type 1 diabetes.

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World Health Day - Eyes On Diabetes

Today is the World Health Organization's World Health Day, and for the first time, the focus is on Diabetes and its global impact.

In Canada, it is estimated that 11 million Canadians are living with diabetes or prediabetes, with 20 Canadians being diagnosed with diabetes every hour.

As per the press release from the Canadian Diabetes Association:

Diabetes increases a person’s risk for many serious complications such as heart attack, stroke, kidney failure leading to dialysis, and blindness. Nevertheless, for many people it is possible to live a healthy, full life with diabetes.

“People with diabetes play a critical role in ensuring the best health outcomes with the disease. Working closely with their health-care team, they manage blood sugar levels, foot care, eye care, physical activity and healthy eating,” says Dr. Jan Hux, chief science officer at the Canadian Diabetes Association (CDA). “Self-management is the cornerstone of diabetes care and people affected by it need the knowledge and skills to properly manage diabetes.”

According to the CDA’s Report on Diabetes: Driving Change, access to diabetes education is vital for learning more about nutrition, physical activity, blood sugar monitoring, medication and ways to make even little changes that can lead to success.

Some tips to keep on top of your diabetes include: taking action to learn as much as possible and using diabetes programs and services when needed; setting your targets and goals to maintain optimal average (A1C) and daily blood sugar levels; performing self-checks for foot problems; and scheduling regular eye exams. For more information, visit diabetes.ca/takecharge. 

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Liraglutide Reduces Heart Disease In People with Type 2 Diabetes

BIG news in the diabetes world was released on Friday - for the first time, a medication in the class called GLP-1 receptor agonists, called liraglutide (trade name Victoza), has been shown to reduce cardiovascular events in people with type 2 diabetes.

The LEADER trial enrolled over 9000 people with type 2 diabetes, who were at high risk of cardiovascular disease, and randomized them to receive either Victoza vs placebo with usual standard of care.

They found that Victoza was better than placebo to reduce the combination of death from cardiovascular disease, non-fatal heart attack and non-fatal stroke. A reduction in all three of these components contributed to the benefit that was seen.   The numbers and details are not yet available - we'll have to wait until the American Diabetes Association meeting in June to find out more.

Here's why this is ground-breaking news: 

We have long been uncertain whether we are actually preventing cardiovascular disease by treating diabetes - we know that the higher sugars are, the higher the risk of heart disease, but it has been evasive to actually prove that lowering blood sugars prevents heart disease. The next question is whether some medications to treat type 2 diabetes could be better (or worse) than others to protect from heart disease.  LEADER has now shown us that treating type 2 diabetes with liraglutide does indeed protect patients from cardiovascular events.

Within the GLP1 receptor agonist group of medications, a study of lixisenatide (called the ELIXA study) showed that it did not increase the risk of cardiovascular events, but it didn't prevent them either.  Studies of the other GLP1 receptor agonists available are currently underway.

As far as other type 2 diabetes medications go, the only other medication that has clearly been shown to reduce cardiovascular disease is empagliflozin, which you can read more about here and here.  Metformin, which is the #1 treatment advised for type 2 diabetes worldwide, has some weak evidence that it prevents cardiovascular events as well.

We will be waiting in anticipation for more details from the LEADER trial in June!


Disclaimer: I have been involved in research trials of liraglutide.  I receive honoraria as a continuing medical education speaker and consultant from the makers of liraglutide (Novo Nordisk). I am involved in research of medications similar to liraglutide for the treatment of type 2 diabetes.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2016

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The Legacy Effect 30 Years Later - Good Control of Diabetes Prevents Heart Disease

A lot of people with diabetes wonder why their doctors and diabetes educators are seemingly obsessed with keeping blood sugars as close to normal as we can.  After all, blood sugars that are only mildly elevated usually don't come with much in the way of symptoms.

The point to keeping sugars as well controlled as possible is to prevent complications of diabetes developing over time - this includes damage to the eyes, heart, kidneys, and nerves in the feet and elsewhere in the body.

And - a new paper published has now shown us that the benefit of good control of diabetes to prevent cardiovascular disease persists for at least thirty years!

The study, which was recently published in the journal Diabetes Care, evaluated patients 30 years after their initial participation in the famed (well, famous in the diabetes world anyway) DCCT trial.  This was a clinical trial that enrolled 1,441 patients with type 1 diabetes, and assigned them to receive either more intense, or less intense, control of their blood sugars for a mean of 6.5 years.

During the 30 years of follow up, they found that the people who were in the tightly controlled group 30 years previously had a 30% reduction in the risk of developing cardiovascular disease, and a 32% reduction in the likelihood of having a heart attack, stroke, or dying from a cardiovascular cause, compared to those who were in the less tightly controlled group.  The tighter blood sugar control during the time of the original 6.5 year study was statistically responsible for all of the difference in cardiovascular disease between the two groups.

This data really impresses upon us the power of what we call the 'legacy effect' - good control of diabetes early on prevents complications later in life.  (Note: there is a similar trial in type 2 diabetics called the UKPDS study, which also showed that the legacy effect exists 10 years later.)

I think it is challenging for anyone to look forward 30 years into the future, and think about the importance of what we are doing now to our future self.  If you think about it, we actually spend a lot of our lives planning for our 30+ year future self.  Take financial planning, for example - most of us structure our home purchases, savings structures, and investments with the goal of planning for the distant future.  As I see it, planning for our health in the future is no different - and for people with type 1 diabetes, we now have very long term data to back this up.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2016

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Natural Remedy Star Fruit Causes Kidney Damage

It is often in my day that people tell me that they are taking natural remedies for any number of medical conditions - for aches and pains, diabetes, obesity, cancer prevention... the list goes on.  The thinking that often underlies the decision to take these remedies is that they are natural, so how could they possibly be harmful?

I worry about my patients taking natural or naturopathic products, because rigorous clinical trials are not done to show benefit, nor (most concerning) to understand potential harms.  So, when I came across two very serious case reports of kidney damage from the seemingly innocent star fruit, I wanted to share it to illustrate the potential dangers of natural remedies.

Star fruit comes from a tree native to India and southeast Asia.  In addition to eating them as a fruit (I've enjoyed them myself on occasion while traveling to these areas), they are also touted as a herbal remedy for various ailments (including diabetes) in these countries.

Recently, two cases of star fruit toxicity were published.  One case was that of a woman with type 2 diabetes who consumed 200 mL of star fruit juice (less than a cup) from six star fruits, which resulted in kidney failure due to an inflammatory reaction in the kidneys (acute interstitial nephritis) caused by the high oxalate content of star fruit.  Thankfully, with medical treatment, her kidneys recovered.

The second case was that of a man with a history of moderate kidney dysfunction, who developed kidney failure after eating four star fruits over four days.  Thankfully, he also recovered after about 2 weeks.

In addition, like the grapefruit, star fruit also inhibits a group of liver enzymes (cytochrome P450 isoforms) which are important for metabolism of medications such as statins (cholesterol medications).  This is why it is advised for patients on statins not to eat grapefruit - star fruit should be included in this counselling as well.

So, take these cases into consideration the next time you think about reaching for a herbal remedy - remember that we simply do not know enough about these remedies to know if they are safe.

As a patient, be sure to tell your doctor about any natural remedies you are taking.

As a health care professional - remember to ask.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2016

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