Could Antacid Medications Affect Blood Sugar Control in Diabetes?

Proton pump inhibitors (PPIs) are medications commonly prescribed to treat heartburn and peptic ulcer disease [eg omeprazole (Losec), pantoprazole (Pantoloc), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Pariet)].    Since PPIs work by blocking acid secretion in the stomach, and since a higher acid content of food lowers its glycemic index, I was asked whether PPIs could increase the effective glycemic index of a meal and thus have a negative impact on diabetes control.

It turns out that PPIs have a very interesting relationship with pancreatic function and blood sugars.

Firstly, as PPIs work by blocking acid secretion in the stomach,  PPIs do increase the pH in the stomach and very high up in the small intestine (proximal duodenum).  However, there is little to no effect on pH in the majority of the small intestine, where carbohydrates are absorbed.

PPIs raise serum levels of a hormone called gastrin, which is responsible for stimulating acid secretion in the stomach.  This is because the gastrin secreting cells in the stomach sense that acid production is low, so more gastrin gets cranked out in an attempt to increase acid secretion.

Interestingly, gastrin stimulates glucose-induced insulin secretion from the beta cells of the pancreas.  There is also some experimental evidence that gastrin may stimulate the production of new beta cells.   Further, PPIs slow emptying of the stomach, because less acid in the stomach means that it takes longer for solid food to be broken down and be ready to pass into the small intestine.

So, based on these mechanisms, it seems that PPIs could possibly have a benefit to blood sugar levels.  While the studies on this are still quite limited, the available evidence suggests that PPIs could lower A1C (a marker of diabetes control) by 0.5% to as much as 1% - possibly as much as a diabetes medication!

PPIs are medications that have benefits but also potential risks, including increased risk of gastrointestinal infections, malabsorption of important micronutrients like calcium, magnesium, vitamin B12, and iron, increased risk of fracture, changes in gut bacteria, and others (note this list is not exhaustive), and they should not be prescribed for the purpose of blood sugar control.

That being said, I will be watching blood sugar control with extra interest the next time one of my patients with diabetes is started on a PPI for their gastrointestinal issues.

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Testing Blood Sugar - Is There A Point?

In the management of people with diabetes, we routinely equip patients with glucose meters and ask them to check sugars at home.  While the importance and utility of checking sugars at home for people using insulin is clear, there is much debate about whether this is useful for people with type 2 diabetes who are not on insulin.  A recent study, which got a lot of media hype, tackled this question.

The study, published in JAMA Internal Medicine, randomized 450 people with type 2 diabetes and not using insulin, to either a) no home glucose montoring; b) checking sugars once daily; or c) checking sugars once daily plus automated educational/motivational messages delivered to the patient from the meter.

The researchers found that there was no difference in diabetes control (A1C) nor health related quality of life after 1 year, and concluded that glucose monitoring in people with non-insulin-treated type 2 diabetes should not be routine.

I have some major beefs with this conclusion:

1.   Testing once a day does not tell a person very much about their blood sugar.   In order for home testing to be useful, I advise 'paired meal testing': checking before a meal, and checking again 2 hours later.  This can be very helpful to see how certain types of food affect your blood sugar, and can be help to eat mindfully and manage portion control.  I don't necessarily advise doing this every day: checking each of breakfast, lunch, and dinner once per week can be enough.  However, depending on what kind of medication a person is taking, I may recommend more often.  Also, if diabetes control is not great, then checks (in my opinion) should be done more frequently so that we can figure out how to bring down the sugars effectively and safely.

2.  As the authors note, the study was not powered to determine if there are benefits to checking sugars around the time of medication or dose changes.  It is very difficult for a doctor to know what the next best medication may be without knowing the pattern of blood sugars through the day.  Knowing the pattern of blood sugars is extremely important when new medications are added onto sulfonylureas and insulin in particular, because these medications can cause low blood sugar.  For example, if sugars are highest in the morning and lower later in the day, there is a risk of causing low sugars if a treatment is added that brings down sugars in the morning (as sugars later in the day will go down too).

3.  Compliance with sugar checks in the study was poor by one year, declining gradually over the year, with only about 55% of people in the monitoring groups checking sugars each day by the 1 year mark.  Interestingly, the diabetes control (A1C) was better at 3, 6, and 9 months in the glucose monitoring groups, compared to those not monitoring - perhaps the lack of difference in A1C by 1 year was due to the poor compliance with glucose checks by that point in time.

4.  The study team did not engage with patients after their baseline visit - meaning patients were on their own to interpret their blood sugars without help from the study team.  Their family doctors received a copy of blood sugar results, but the study did not collect info on what was done with that data, and these clinicians had minimal interaction with the study team.  

Diabetes is a team sport - an important part of the benefit of checking blood sugars is to discuss these results with your health care team for help in optimizing control.  While the setup of this study was intended to be 'real world', I would submit that what patients perceived as their 'health care team' during the study (their usual doctors plus study investigators) were not working as a team and this may have limited the best possible use of home glucose monitoring.  And perhaps compliance with checking sugars in the study would have been better if that team was working together and more engaged with the patients, as is the ideal model of care.  We are blessed in Canada to be able to say that for most people in our country, the 'real world' does consist of free access to a team to help each individual with their diabetes care.

5.  For any patient on a sulfonylurea (and of course insulin), sugars must be checked before driving.   For a paper to conclude that glucose monitoring should not be routine (in a study where 36% of patients were on sulfonylurea!) is inappropriate.

Unfortunately, the media took hold of this study and has been shouting from the rooftops that people with non-insulin-requiring diabetes do not need to check their blood sugar.    I would be most saddened if patients get the message that they should stop testing their blood sugars, and would strongly advise people to continue to follow their doctor or diabetes educator's recommendations on how frequent of sugar checks is appropriate.

I hope this blog helps to provide some balance and perspective on what I feel is a study full of limitations.

Disclaimer: I have received speaking honoraria from makers of glucose meters.

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www.drsue.ca © 2017

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Low Carb Diets Part II: What If I Have Diabetes?

In last week's blog post, we talked about low carb diets, definitions, and whether they work for weight management.  Today we'll discuss low carb diets in people with diabetes: Are they beneficial? Are they safe?

As far as potential benefit goes, the available data are not consistent in their findings.  In a review article published by Feinman and colleagues in the journal Nutrition, data is summarized reporting an improvement in blood sugar control, along with a reduction in medications required to control blood sugars.  However, systematic reviews and meta analyses have not consistently shown improvements in blood sugar control.  At least some of the variability likely has to do with adherence - low carb diets are not easy to stick to for many people.

If a low carb diet is going to be embarked upon, the type of medication that a person with type 2 diabetes is taking to control blood sugars is very important to consider.   Medications that can cause low blood sugars [insulin; sulfonylureas such as gliclazide (Diamicron) and glyburide; and meglitinides (eg Gluconorm)] may need to be decreased with the help of your health care provider, in order to avoid low blood sugars.

SGLT2 inhibitors are a class of medications to treat type 2 diabetes, which are associated with a risk of 1 in 1000 people per year developing diabetic ketoacidosis (DKA), which is a type of acid buildup in the blood that is life threatening. For people on these medications [canagliflozin (Invokana), dapagliflozin (Forxiga), empagliflozin (Jardiance)], low carbohydrate diets are associated with an increased risk of DKA.  As to whether a mildly low carb diet is safe is not known, as there is very little data available in this area.  One small study did show an increase in ketones in people with type 2 diabetes on an SGLT2 inhibitor on just a very mildly restricted carbohydrate diet (40% calories, as compared to people on a 55% carb calorie diet), but how much this may increase the risk of DKA is not known.

A ketogenic diet should be avoided for anyone with type 2 diabetes on insulin or SGLT2 inhibitors, because of the risk of ketoacidosis.

For people with type 1 diabetes, there is very limited data on which to guide us.  There is some data suggesting that a low carb diet may improve hemoglobin A1C (a marker of blood sugar control).   However, there is a concern that there may be a blunted response to glucagon as an emergency treatment for severe low blood sugar in people with type 1 diabetes following a low carb diet.

A ketogenic diet should be avoided for anyone with type 1 diabetes due to the increased risk of ketoacidosis.

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Will Bariatric Surgery Help Me Control My Diabetes?

One of the major reasons why we might suggest bariatric (obesity) surgery to our patients with obesity and type 2 diabetes, is that studies have shown bariatric surgery to be very effective in improving diabetes control, or even putting diabetes into remission.  However, it has been slow to grow the body of research data in this area, as it is difficult to conduct high quality, long term studies in this field.

Now, just published, we have 5 year data showing that bariatric surgery (gastric bypass surgery and sleeve gastrectomy) are superior to medical therapy to treat type 2 diabetes in people with obesity.

I blogged on the 3 year data in this trial, called the STAMPEDE trial, when it came out in 2014 - where you can read about the structure, goals of the study and the results at that time.

Now, published in the New England Journal of Medicine, the extended results of the STAMPEDE study show that 5 years after bariatric surgery, 29% of patients who had gastric bypass surgery had tight control of their diabetes, vs 23% of those who had sleeve gastrectomy, vs only 5% of those who had intensive medical treatment alone.  A duration of diabetes of less than 8 years before surgery was the main predictor of achieving tight control of diabetes, suggesting that earlier intervention with bariatric surgery may give the maximum benefit in glycemic control.

There were also greater improvements in body weight, several measures of cholesterol, need for insulin, and quality of life in the surgical groups.  No late major surgical complications were reported except for one person in the sleeve gastrectomy group who underwent gastric bypass at year 4 to treat a gastric fistula.  Follow up at the 5 year mark was 90%, which is excellent.

While I still take issue to the target for diabetes control being too tight in this study at an A1C of 6.0%, this study does now give us good 5 year data to support that bariatric surgery can be an effective tool to help treat type 2 diabetes in people with obesity.

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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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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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