Could Antibiotics Cause Diabetes?

The more we learn about type 2 diabetes, the more we appreciate that there are many, many factors that play into the development of this complex medical condition.  The bugs that live in our intestines (called microbiota) are falling under increased scrutiny in how they affect our metabolism.  A new study suggests that antibiotic use (which changes our microbiota) increases the risk of type 2 diabetes.

The study, conducted by Mikkelsen and colleagues and published in the Journal of Clinical Endocrinology & Metabolism (a journal that we endocrinologists love to geek out over) looked at 12 years of data from the entire population of Denmark.  They found that those who had filled 2-4 prescriptions for antibiotics has a 21% higher risk of having type 2 diabetes, compared with those who had filled 0-1 antibiotic prescriptions.  The higher the frequency of antibiotic usage, the higher the risk of having type 2 diabetes. The higher use of antibiotics in type 2 diabetes patients was seen for up to 15 years before the diagnosis of type 2 diabetes, as well as after the diagnosis of diabetes.  

So does this clearly tell us that antibiotics destroy our gut bacteria and cause diabetes?  No.  The data could also be interpreted to reflect that diabetics (diagnosed or not yet diagnosed) are at higher risk of infection, therefore more likely to need antibiotics.  That being said, the fact that the association between antibiotic use and diabetes was seen for up to 15 years before diabetes was diagnosed, makes it unlikely that these data simply reflect diabetics needing treatment for infections. (while diabetes has often been present 5-7 years before diagnosis, 15 years of undetected diabetes is unlikely). 

We are still in the early stages of understanding how our gut bugs affect our metabolism, but there is increasing evidence that they play an important role not only in the development of obesity, but also potentially in the development of type 2 diabetes. I will be watching this area with interest!

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2015 

Read more...

Diabetes Medication Empagliflozin Saves Lives

In follow up to the press release I blogged about last month, we now have the data which has rocked the foundation of the diabetes world:  the diabetes medication empagliflozin has been found to reduce the risk of cardiovascular deaths and all cause mortality in patients with type 2 diabetes and cardiovascular disease.

The EMPA-REG study, published by Canadian Dr Bernie Zinman and colleagues in the New England Journal of Medicine, randomized 7020 people with type 2 diabetes and established cardiovascular disease to receive either empagliflozin 10mg, empagliflozin 25mg, or placebo, in addition to their usual care.

After a median of 3.1 years, they found that there was a significantly lower risk of death from cardiovascular causes (3.7% on empagliflozin vs 5.9% in the placebo group), a reduced risk of death from any cause (5.7% on empagliflozin vs 8.3% on placebo), and a reduction in hospitalization for heart failure (2.7% on empagliflozin vs 4.1% on placebo).

Put another way: empagliflozin decreased the risk of hospitalization for heart failure by 35%, reduces the risk of death from cardiovascular causes by 38%, and reduced the risk of death from any cause by 32%.

Put yet another way:  if 39 people were treated with empagliflozin for 3 years, one death was prevented.  This number is very comparable to the power of other medications that we use to prevent cardiovascular disease and death in people who are at high risk:  for example,

• simvastatin (a cholesterol medication): treating 30 people for 5.4 years prevents one death
• ramipril (a blood pressure medication): treating 56 people for 5 years prevents one death

These results are truly landmark, in that we have never before definitively proven that any diabetes medication clearly reduces the risk of cardiovascular disease or death.  There are two other medications in this class of diabetes medications (called SGLT2 inhibitors) which are available in Canada (canagliflozin (Invokana) and dapagliflozin (Forxiga)).  These medications have similar studies underway, but results are still a couple of years away. 

The EMPA-REG results have caused diabetologists around the world to have to reconsider current practice guidelines for type 2 diabetes, and whether this class of medications should take priority in the selection of treatment for our patients.   While it is always of paramount importance to consider benefits and risks of any medication, this data certainly suggests that the SGLT2 inhibitors should be considered high on our list of choices for treatment of type 2 diabetes.

Disclaimer: I receive honoraria as a continuing medical education speaker and consultant from the makers of empagliflozin (Boehringer-Ingelheim and Eli Lilly), canagliflozin (Janssen), and dapagliflozin (Astra Zeneca).  I am involved in research of SGLT2 inhibitors as a treatment of diabetes.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2015

Read more...

Diabetes Medication Empagliflozin Reduces Cardiovascular Events

BIG news in the diabetes world this week - empagliflozin, a medication used to treat Type 2 Diabetes, is the first diabetes medication to show a reduction in cardiovascular risk in a rigorous clinical trial.

The EMPA-REG trial enrolled over 7,000 type 2 diabetic patients who were considered to be at high risk of cardiovascular events and had suboptimally controlled diabetes, and randomized them to received either empagliflozin 10mg, empagliflozin 25mg, or placebo.  The primary outcome was time to first occurrence of cardiovascular death, non fatal heart attack, or non fatal stroke.  Treatment with empagliflozin was in addition to usual standards of diabetes care.

The trial found that empagliflozin reduced the risk of cardiovascular events compared to placebo.  I would love to look at further details today - but the data is embargoed until the European Association for the Study of Diabetes (EASD) meeting in Stockholm on September 17th.  Data on just how much CV events are reduced, or which patients may benefit most, is not yet available.

Empagliflozin (trade name Jardiance) is one of a class of newer type 2 diabetes medications called SGLT2 inhibitors.  They block the kidneys' ability to reabsorb sugar from the urine back into the bloodstream, with the result that sugar is excreted in the urine (ie it causes you to pee sugar).  In addition to reducing blood sugar and improving diabetes control, these medications also reduce blood pressure (they have a diuretic like activity) and also cause an average weight loss of around 10 lbs.  Another excellent feature is that they do not cause low blood sugars as a side effect.  While the details of the EMPA-REG trial haven't been released yet, it is likely that all of these mechanisms of action contribute to the reduction in CV risk that was seen.

Empagliflozin has just been approved in Canada and will be available on shelves soon.  Canagliflozin (trade name Invokana) and dapagliflozin (trade name Forxiga) are available already.  The clinical trials of canagliflozin (called the CANVAS trial) and dapagliflozin (DECLARE trial) are currently underway, with results expected in a few years' time.  Clinical trials of other classes of type 2 diabetes medications are also underway, with results also rolling out over the next few years.

Until now, we have not had robust evidence that any particular diabetes medication clearly decreases the risk of CV events.  Metformin has some less robust data behind it in this regard; this data is one of the main reasons why it is considered the first line treatment for type 2 diabetes worldwide.   As the data and details of this study (and the other studies of medications in this class) become available to us, it will be interesting how these results may change the shape of how we approach type 2 diabetes treatment.


Disclaimer: I receive honoraria as a continuing medical education speaker and consultant from the makers of empagliflozin (Boehringer-Ingelheim and Eli Lilly).  I am involved in research of SGLT2 inhibitors as a treatment of diabetes.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2015

Read more...

Fatty Liver - A Dangerous Complication Of Obesity

Amongst the long list of medical complications of obesity, one very common complication that is not considered often enough is fatty liver.

Non alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide.  It is divided into:

• fatty liver (fat deposition) only
• fatty liver with inflammation (steatohepatitis)
• fatty liver with inflammation and scarring (fibrosis), which in the most severe cases is called liver cirrhosis 

A recent review by Mary Rinella in the Journal of the American Medical Association (JAMA) reports some sobering statistics on this problem:

• non alcoholic fatty liver disease (NAFLD) affects 30% of the American population - in other words, between 75 million to 100 million Americans likely have this disease
• liver cirrhosis is the third most common cause of death in patients with NAFLD
• 66% of patients age 50 or older with diabetes or obesity are thought to have advances fibrosis (scarring) of the liver

The diagnosis of NAFLD presents a number of challenges.  Liver enzyme tests (ALT and AST) are normal in 30-60% of patients with fatty liver plus inflammation (steatohepatitis) on liver biopsy, so we clearly cannot rely on these blood tests to make the diagnosis.  Ultrasound can catch many cases of fatty liver, but can miss the milder ones.  MRI is the best non invasive test to detect fat in the liver, but is unfortunately expensive and in limited supply.  

To look for scarring (fibrosis) in the liver, a special kind of test called a Fibroscan (vibration-controlled transient elastography) can be done in a liver specialist's office and is fairly accurate.  MRI elastography may be more reliable, but again is costly and not widely available.  

The best test to look for fatty liver, inflammation, and scarring is a liver biopsy - but of course, this is not without risk.  

In terms of treatment, the only good therapy we are currently aware of is weight loss.   A weight loss of 10% has been shown to decrease liver inflammation.  It also appears that a lower carbohydrate diet is important.  Vitamin E has been shown to have some benefit, but may be associated with a higher risk of prostate cancer and hemmoragic (bleeding type) stroke.  A number of medications have been looked at (including pentoxyfylline, obeticholic acid, and pioglitazone), but none have been found to be sufficiently effective, and/or have too high of a side effect risk profile. 

It is important for health care providers to consider fatty liver as a possible medical condition in any patient with obesity.  As for treatments, we have a long way to go, but the importance of healthy lifestyle changes seems more important than ever.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2015

Read more...

Could Artificial Sweeteners Cause Diabetes?

Artificial sweeteners are commonly touted as a healthy alternative to natural sugar. Sweeteners contain low to no calories (read about the types of sweeteners here), and they do not make blood sugars spike in diabetics.   However, a growing body of research lends a growing amount of concern to possible negative side to artificial sweetener use. 

A fascinating set of studies was collected and published recently in Nature, looking at how artificial sweeteners affect the bacteria in our intestines, and how these effects in turn may actually increase the risk of developing diabetes or pre-diabetes.  For the scientist with a couple of hours and a day with a good attention span may want to read the article for themselves – it’s heavy but super.  Here are the key results of their studies:

Both lean and obese mice who were fed artificial sweetener (saccharin, sucralose, or aspartame) were more likely to develop prediabetes compared to mice fed glucose or sucrose. (read more about different types of sugar here).

They showed that the development of prediabetes in these mice was caused by a change in the types of bacteria in the mice’s intestines.  These altered bacteria are better at making calories from food accessible for absorption, meaning that mice (or humans) more readily absorb these calories, thereby contributing to higher blood sugars (and probably weight gain as well).

In humans, survey type studies have shown that people who use artificial sweeteners are more likely to be people with weight struggles and diabetes, but whether the artificial sweeteners cause these problems, or whether it is simply that people who have these problems are more likely to consume artificial sweeteners to help fix these problems, is difficult to separate.    The authors therefore looked at a very small group of seven study participants who didn’t normally consume artificial sweeteners, and they found that when they ate artificial sweeteners for a week, four of the seven participants developed an increase in their blood sugars by the end of the week.  An examination of these people’s stools (oh yes they did) showed a marked change in the bacteria growing in their intestines after a week of artificial sweeteners. When they transplanted the stool of the people who developed higher blood sugars into mice (oh yes they did), the mice then went on to develop higher blood sugars as well.

So, in summary, these elegant studies suggest that artificial sweeteners may change the types of bacteria that grow in our gut, to types of bacteria that cause us to absorb more calories from food into our bloodstream, with the increase in sugar absorption increasing the risk of diabetes.  

So what is the best solution?  Eating added natural sugar undoubtedly increases our risk of diabetes, obesity, and metabolic syndrome, and there is now emerging evidence to suggest that artificial sweeteners may not be good for our metabolism either.

The best answer is to avoid adding added sweetener period, be it sugar or artificial sweeteners. 

Thanks to my friend and colleague, Pam, for the heads’ up on this article.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2015

Read more...

ENDO 2015: Diabetes and Bones

And....we're off!!! ENDO 2015 is off to a fabulous start.  I'm excited to share with you our learnings about diabetes and bone disease from a symposium held this morning.  You'll need a few extra minutes to read this post - it's a little longer than my usual blogs - so much to cover and share!  Grab a cuppa and get comfy. :)


We were first provided an overview of the impact of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) on the skeleton, by Dr Ann Schwartz.  We learned that diabetics are at an increased risk of fracture (broken bones) than people without diabetes. In T1DM, bone density is lower than in non diabetics, suggesting a moderately increased risk of hip fracture.  However, studies have shown that a type 1 diabetic is actually at over a 6 times higher risk of a hip fracture compared to a non diabetic (much higher than differences in bone density would suggest), suggesting that there is much more to the story than a lower bone density.

In type 2 diabetics, the situation is different.  As 90% of T2DM patients struggle with overweight or obesity, bone densities are higher, a result of the higher body weight that the skeleton supports. Despite this, T2DM patients are at 40% higher risk of hip fracture; after adjusting for body mass index (BMI), there is a 70% increased risk of hip fracture compared to non diabetics.  

While diabetics are at a higher risk of falls (see below for more thoughts on this), studies that controlled for falls still show a higher fracture risk – again suggesting that there is something going on in the bones themselves that increase fracture risk.

So why are diabetics at a higher risk of fracture for a given bone density?  Many possibilities have been suggested in terms of differences in bone structure at the microarchitectural level, but as Dr Mary Larsen Bouxsein pointed out, there is little that is currently understood about exactly what is happen at the microscopic level in terms of the damage that high blood sugars could be doing to bone.  Dr Josh Farr showed us data suggesting that cortical bone microarchitecture in women appears to be compromised in T2DM due to decreased bone formation and turnover, but these studies are limited by size and data are not available in men.

As diabetics have a higher fracture risk for a given bone density, our traditional means of evaluating fracture risk may not be appropriate.  It has been shown that bone density testing (using the T score) does predict risk of hip fracture in diabetics, but at a particular T score, the fracture risk is higher than a non diabetic with the same T score.  The FRAX score, which we often use to predict risk of fracture in our patients, underestimates the risk of fracture in T2DM.

Medications that treat type 2 diabetes may have variable effects on bone as well, as reviewed by Dr Christian Meier.  Metformin, our first line treatment for type 2 diabetes, seems to be protective of the bones.  We know that the group of medications called thiazolidinediones increase the risk of fracture in postmenopausal women and older men, and with longer duration of treatment. There is some evidence to suggest that the group of type 2 diabetes medications called incretin therapies may be protective of bone, but much further study needs to be done.  A newer class of medications called the SGLT2 inhibitors may slightly increase fracture risk, but again, much more study is needed in this area.

A few important points that I would like to highlight (from this session, as well as my own thoughts):  

• It is crucially important to avoid low blood sugars in patients with diabetes.  A low blood sugar can cause a fall that can result in a fracture.  
• Prevention of diabetic nerve damage is also crucial, as fall risk increases in those who have loss of sensation to their feet.  
• Being fit and strong is also important to prevent falls. 
• Finally, checking vitamin B12 in patients on metformin is important as well, as low vitamin B12 can cause nerve damage, and metformin can rarely cause vitamin B12 levels to be low.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2015

Read more...

Sniffing Out Inhaled Insulin

In an effort to find alternative ways to administer insulin apart from the current standard of injecting it under the skin, a new inhaled insulin has recently been made available in the United States.

Called Afrezza, the inhaled insulin is taken at mealtime, and is used instead of fast-acting insulin injection at mealtimes (it does not replace the need for long acting insulin in those who need it).  It is rapidly absorbed by the lungs, has its peak action at under an hour, and is gone in 2.5 to 3 hours (a little faster than the fast acting mealtime injectable insulins currently available).

While clinical trials have been done, showing that the inhaled insulin is comparable in efficacy to mealtime injectable insulin in type 1 and type 2 diabetics, these studies have been criticized in that diabetes control in these studies was not as tight as recommended by diabetes guidelines (ie, hemoglobin A1C of 7% or less).  


There are a number of additional concerns with inhaled insulin, including:

1.  Dose increments are large (it has to be adjusted by 4 unit increments, whereas injectable insulin can be adjusted by as little as 0.5 unit increments).  This makes it harder to fine-tune blood sugar control.

2.  Inhaled insulin cannot be used in smokers or people with lung disease (such as asthma).

3.  Inhaled insulin causes a small decrease in lung capacity (forced expiratory volume).   Lung function has to be monitored in people using inhaled insulin.


My take:  Due to the concerns above, I don't see this as a game changer in diabetes care.  Should this inhaled insulin become available in Canada, I will continue to recommend the currently available injectable mealtime insulins to my patients.  That being said, for people who are very resistant to the idea of taking an injectable mealtime treatment, this could offer an (inferior) alternative way to give insulin to those people - ie, it may be a better alternative to no mealtime insulin at all in people who need it.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2015

Read more...