Bariatric Surgery - Can We Predict Remission Of Diabetes?

One of the most important benefits of bariatric surgery (especially gastric bypass and sleeve gastrectomy) is its ability to improve the control of type 2 diabetes, often to the point where type 2 diabetes actually goes into remission after surgery.  Not everyone with type 2 diabetes who has bariatric surgery will experience remission - about 70-80% of patients having gastric bypass and about 50-60% of patients having sleeve gastrectomy will experience remission.  Ideally, we would be able to predict the likelihood of diabetes remission before the surgery is done, as this is arguably one of the most important potential benefits of bariatric surgery.

A recent study tried to answer this question using a scoring system called the DiaRem Score, which looked at at 4 preoperative variables amongst a group of 407 patients who underwent gastric bypass surgery:

• age
• need for insulin 
• diabetes medication use (points assigned varied by type of medication)
• hemoglobin A1C (a blood test which is a 3 month report card of diabetes control)

They found that this score, which is based on the above 4 variables, was highly predictive of who went into remission from their type 2 diabetes and who did not.

Other scoring systems and variables have been looked at as well.  Other variables that stands out in the literature are a shorter duration of diabetes, and preoperative serum C peptide level, which is a marker of a person's ability to produce insulin.

It is exciting to know that as we learn more about bariatric surgery, that we can become better at predicting who may benefit from a diabetes standpoint.  However, a word of caution - longer term studies suggest that for people who do enjoy diabetes remission after bariatric surgery, the diabetes recurs in about 50% of these people by 5 years post op.  While there is still certainly a health benefit to being free of diabetes for a number of years, it is important to remember that the diabetes can return and must be screened for regularly and lifelong.

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Marijuana and Diabetes Risk - Friend or Foe?

In follow up to my blogs about the increased risk of diabetes associated with smoking (read more here), some of my colleagues have asked me to comment on whether there is also an increased risk of diabetes associated with marijuana use.  With the advent of medical marijuana, and the plans to legalize marijuana use in Canada, this is definitely an excellent question.

A question, which it turns out, we have very little data on which to base an answer.

One study examined body fat, insulin sensitivity, and various aspects of beta cell function (the pancreatic cells that make insulin) in 30 cannabis smokers, and compared them to people matched for age, gender, ethnicity, and body mass index. They found that cannabis smokers had a higher percentage of abdominal visceral fat (the fat around the organs that is the metabolically dangerous (diabetes inducing) fat).  Good cholesterol (HDL) was a little lower, and carbohydrate intake a little higher, but otherwise, there was not much difference between groups.

Another study evaluated metabolic parameters in 4657 adults from the American NHANES (National Health and Nutrition Examination Survey), 579 of whom were current marijuana users. They found that current users had a 16% lower fasting insulin level, and had less insulin resistance as well  (17% lower HOMA-IR, for the scientists in the audience), suggesting a lower risk of developing type 2 diabetes. Use of marijuana in this study was associated with smaller waist (a crude way to measure abdominal visceral fat - which contrasts with the findings in the first study above).

Other than these studies, there is very little data on marijuana and its effect on diabetes risk.

At this point, the available data does not suggest that marijuana carries the increased risk of developing diabetes that cigarette smoking does, with one study suggesting that it may even be protective of developing diabetes. However, the data is extremely limited, and further study of the effects of marijuana is much needed.

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Diabetic Neuropathy

One of the main reasons why long term blood sugar control is so important in diabetes is the prevention of diabetes complications.   Diabetic neuropathy, which is damage to nerves caused by chronic elevation in blood sugars, is one of the complications we are trying to prevent.   Diabetic neuropathy affects a lot of people (you may be surprised by just how many - read on!), can be present in people who don't even have diabetes yet, can take many different forms, and can have a profound impact on the quality of life of people living with diabetes.

The American Diabetes Association has recently released a Position Statement (download is free) to help guide clinicians in understanding, diagnosing, preventing, and managing this complication of diabetes.

Some key points from this article:

1.  Diabetic neuropathy (DN) is a diagnosis of exclusion.  In other words, just because a patient with diabetes has findings of neuropathy, doesn't mean that the diabetes is necessarily the cause.  Other causes of neuropathy (discussed in the article) need to be ruled out before the nerve problem is attributed to diabetes as the cause.

2.  There are many types of diabetic neuropathy.  Distal symmetric polyneuropathy usually starts with symptoms in the feet, including numbness, tingling, pain, and burning, especially at night.  Autonomic neuropathies can affect/include the heart, ability to maintain blood pressure when standing up (orthostatic hypotension), the gastrointestinal tract, urinary tract, sexual dysfunction, or dysfunction in sweating. There are also forms of diabetic neuropathy that can affect specific nerves (cranial or peripheral), or bundles of nerves as they exit the spinal column.

3.  Diabetic neuropathy is common. Distal symmetric polyneuropathy affects 50% of people with type 2 diabetes after 10 years, and 20% of people with type 1 diabetes after 20 years.  Autonomic neuropathy involving the heart may affect up to 60% of people with type 2 diabetes after 15 years, and up to 30% of people with type 1 diabetes after 20 years.

4.  Diabetic neuropathy can be present in people with prediabetes.  Distal symmetric polyneuropathy may be present in 10-30% of people with impaired glucose tolerance, and autonomic neuropathy affecting the heart has been found in people with impaired glucose tolerance as well.

5.  Prevention of diabetic neuropathy is key, as there is no effective treatment available for established nerve damage.  Prevention is achieved primarily through optimizing blood sugar control. Lifestyle interventions are recommended for prevention in people with prediabetes or type 2 diabetes, and a multifaceted approach including targeting of cardiovascular risk factors is recommended for prevention of cardiac autonomic neuropathy in people with type 2 diabetes.

6.  Management of established diabetic neuropathy is directed towards the particular type of neuropathy each patient has.  This can include pain control medication, fall prevention, and specific treatments to manage symptoms of the autonomic neuropathies.

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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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www.drsue.ca © 2016

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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). 

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2016

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