Benefits of Continuous Glucose Monitoring With Insulin Injections in Type 1 Diabetes

In people with diabetes, continuous glucose monitoring (CGM) is an alternative to checking sugars with frequent finger pokes.  CGM is available as a stand alone tool, or can be integrated with an insulin pump system.  Most studies showing the benefits of CGM were done in people using insulin pumps.  Now, two studies show the benefits of CGM in people with type 1 diabetes using insulin injections to treat their diabetes.

The first study, published in JAMA, randomized 158 people with type 1 diabetes using insulin injections to use of either the usual form of self blood glucose monitoring (finger pokes) vs CGM.  At 6 months, the hemoglobin A1C (a marker of diabetes control) was 0.6% lower in the people using CGM compared to those using finger pokes.   People using finger pokes to check sugars during the study were also wearing a CGM during the study, but they could not access the readings on the CGM, with the purpose being for researchers to analyze what the CGM showed in the people using finger pokes during the study.  Importantly, this analysis found that people using CGM spent 37 minutes less per day with low blood sugar (43 minutes per day, compared to 80 minutes per day for people using finger pokes).

The second study, also published in JAMA, compared the effect of CGM vs finger poke monitoring in the same person, using a crossover design.  Patients were randomized to use either CGM or finger pokes for 6 months, then did the reverse for the next 6 months (with a 17 week break in between).  Amongst these 161 patients with type 1 diabetes, hemoglobin A1C was 0.43% lower during the time of CGM use, and they also reported less fear of hypoglycemia, greater well being and greater treatment satisfaction while using CGM. Patients were hypoglycemic 4.79% of the time while using finger pokes (using data from masked CGMs), vs 2.79% of the time with use of CGM.

One thing that I found particularly disturbing about these studies was the amount of time patients spent with low blood sugars.  While CGM improves upon this, we would ideally like patients with diabetes to have zero hypoglycemia.  CGM units have alarms that alert a patient when blood sugar is low, which can be lifesaving, especially for people who don't feel their low sugars and are at risk of sleeping through a low.  Hopefully improved glucose monitoring technology, as well as better insulins being developed, will help us to reduce lows further.  CGMs are unfortunately quite expensive, though some people are able to get the expense covered - talk to your insurance provider (if you have one) and/or your diabetes educator to find out about your options.

These studies clearly support the potential benefits of continuous glucose monitor (CGM) use in people with type 1 diabetes using insulin injections.

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New Class Of Cholesterol Medication Prevents Heart Attacks

Statin medications have long been the main class of medications that have been recommended to lower cholesterol, as they have been shown to be very powerful to reduce the risk of cardiovascular events.  Now, a new class of medications joins the ranks of statins: the PCSK9 inhibitor evolocumab (Repatha) has been shown to reduce cardiovascular events.

The top-line results of the study, called the FOURIER study, have now been released.  This was a study of 27,500 patients with cardiovascular disease who were already on optimized statin therapy, randomized to receive either evolocumab or placebo.  They found that evolocumab reduced the risk of their primary endpoint, which was the sum of cardiovascular death, non fatal heart attack, non fatal stroke, hospitalization for unstable angina, or coronary revascularization (angioplasty).

I am looking forward to learning more about the results of this trial and the amount by which risk was reduced - these data will be released in March at the American College of Cardiology meeting in Washington DC.  It will be interesting to compare these results to the results of the IMPROVE-IT trial, which showed that the combination of statin therapy with the cholesterol lowering medication ezetimibe lowered the risk of cardiovascular death, major coronary events, or non fatal stroke by 2.0 percentage points compared to statin therapy alone.

It is encouraging to see a new class of cholesterol medications being developed that reduce cardiovascular events.  There are many patients who do not tolerate statin therapy; perhaps the PCSK9 inhibitors may also reduce cardiovascular risk for them (studies on this are currently underway).  PCSK9 inhibitors are extremely expensive, which limits their use in clinical practice.  Perhaps with these data, guidelines will be revised and we may hopefully see more coverage options so that the benefits of PCSK9 inhibitors to reduce cardiovascular events can be more widely enjoyed.

Disclaimer: I have been involved in a clinical trial of PCSK9 inhibition. I have received honoraria as a medical education speaker and consultant from the makers of ezetimibe (Merck).

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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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Mediterranean Diet May Slow Brain 'Shrinkage' With Age

The Mediterranean style of eating seems to be rising above most other dietary plans for its health benefits.  Studies have shown that the Mediterranean diet may reduce the risk of cardiovascular events, and may also decrease the risk of breast cancer. A new study shows that the Med diet may also slow age related brain atrophy (natural 'shrinkage' of the brain with aging).

(Pictured above is the brain of a person in their 20s, compared to a person in their 80s, showing the natural atrophy that happens in the brain over time.)

The study, published in the journal Neurology, examined brain volumes and brain cortical thickness in Scottish people age 73, and followed them for three years until age 76.  They assessed eating patterns using questionnaires at age 70 (three years before the start of the study).   They found that people who reported less adherence to a Mediterranean style of eating had a greater reduction in total brain volume from age 73 to age 76, than those who reported eating in the Mediterranean style.

While this study is of lower quality than the randomized controlled clinical trial showing the cardiovascular and breast cancer benefit, it is another arrow pointing towards the benefits of the Mediterranean style of eating.   While no diet has been shown to be superior to another for weight loss, the health benefits of the Mediterranean diet continue to impress.

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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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