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Diabetes Medication Associated with Heart Disease in Women

Last month, Diabetes Care, a journal of the American Diabetes Association, published an article linking sulfonylurea use to increased risk of cardiovascular disease in women. Sulfonylureas stimulate the pancreas to produce insulin and include glipizide (Glucotrol), glyburide (Micronase), and glimepiride (Amaryl) in the US, as well as gliclazide (Diamicron), available in Great Britain and Australia. Although many newer medications are receiving a lot of attention in the media, sulfonylureas remain among the most widely prescribed diabetes medications on the market. Dr. Steve Parker wrote a nice overview of sulfonylureas  a few years back.

A few pertinent facts about the study referenced above:

  • It was a long-term study following 4900 women for more than 10 years as part of the Nurses’ Health Study
  • Researchers took into consideration confounding variables such as family history of CVD, smoking, duration of diabetes, etc.
  • The association with coronary heart disease (CHD) increased with duration of sulfonylurea use


I find this quite concerning, but I’ve only read the abstract and would like to read the entire study before commenting further. (If anyone is willing to share the full text with me, it would be much appreciated.) However, the well-known side effects of sulfonylureas are precisely what I saw in many patients in my former position as an outpatient dietitian in a large hospital:

  • Hypoglycemia due to incorrect timing with food intake and/or absorption of food. Some (such as glipizide) are designed to work within 30 minutes, but patients often forget and take the medication afterward, which can lead to low blood sugar. In rare cases, people taking sulfonylureas have died from severe hypoglycemia.
  • Increased hunger at and between meals
  • Weight gain secondary to increased caloric intake and hyperinsulinemia 


Contrast these undesirable effects with those of metformin, a diabetes medication which is relatively safe, improves insulin sensitivity, decreases hepatic glucose output, and doesn’t result in hypoglycemia or weight gain. 

A very important point is that sulfonylureas are only used to cover postprandial blood glucose in response to a carbohydrate-containing meal. If minimal carbohydrate is consumed, sulfonylureas aren’t necessary and can definitely cause hypoglycemia. So someone following a very-low-carbohydrate diet would need to discontinue sulfonylurea treatment but might continue taking metformin indefinitely, depending on fasting and postprandial blood glucose levels.

I realize most dietitians and diabetes educators advise people with type 2 diabetes that they should consume the same foods as everyone else and take insulin or insulin-stimulating medications to control the inevitable postmeal rise in blood glucose. But with all of the side effects listed above — and now a potential increase in CHD risk — I think that’s a very misguided approach. It also places a large burden on the beta cells of the pancreas and may increase the rate of disease progression. Let’s compare the risks of these medications to carbohydrate restriction for diabetes control. As long as the diet contains ample protein, healthy fat, plenty of vegetables, and smaller amounts of slow-digesting carbs from foods like nuts and berries, there are essentially no adverse effects than perhaps constipation, which is easily treated. And the benefits of low-carbing for someone with diabetes? No risk of hypoglycemia, increased satiety, and easier weight loss — exactly the opposite of eating a “normal” amount of carbohydrates and taking sulfonylureas or insulin for coverage.

At the Low Carb Down Under conference in Melbourne at the end of September, I said that being respectful and courteous is the best way to convince dietitians and diabetes educators to recognize the benefits of carbohydrate restriction, and I stand by that statement. Remember, up until a few years ago I was one of those dietitians who promoted a low-fat diet with plenty of whole grains. But as we continue to find out about the drawbacks of various diabetes medications — including several of the newer ones —  I understand people’s frustration at being told they’re a necessary part of diabetes management instead of being presented with an alternative solution. Since you’re reading this, I hope you’re someone who has benefitted from a low-carbohydrate lifestyle or would like to. The best that we can do is to continue speaking out and sharing our experiences, knowing that the evidence is on our side and at some point most health professionals will understand that carbohydrate restriction is the best and safest option.

References
1. Li Y, et al. Sulfonylurea Use and Incident Cardiovascular Disease Among Patients With Type 2 Diabetes: Prospective Cohort Study Among Women. Diabetes Care 2014 Aug 22 
2.  Braatvedt GD, et al. The clinical course of patients with type 2 diabetes presenting to the hospital with sulfonyl-induced hypoglycemia.Diabetes Technol Ther 2014 Jul 10 
3. Fonseca V, et al. Determinants of weight gain in the action to control cardiovascular risk in diabetes trial. Diabetes Care 2013 Aug;36(8):2162-8

4. Madiraju AK. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature 2014 Jun 26;510(7506):542-6
5. Feinman, et al. Dietary Carbohydrate restriction as the first approach in diabetes management. Critical review and evidence base. Nutrition 2014 July 16

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16 Comments

  1. Kapka Stovel says:

    Franziska, keep the good work that you are doing
    Kapka

    1. Franziska Spritzler says:

      Thanks, Kapka!

  2. As usual ; great article with huge common sense and respect..you have a unique way of writing that forces the reader to respect your opinion and at the mean time get convinced and as a result follow what you say…thanks a lot..

    1. Franziska Spritzler says:

      Thank you so much for your very kind words, Ahmed! I truly appreciate your feedback and support.

  3. Thank you Franziska for the great article and important information. Easy to absorb and super useful. Thank you!!

    1. Franziska Spritzler says:

      Thanks very much, Kelly! Appreciate it 🙂

  4. Alison Brebner says:

    At last a voice of reason …I have been following a low carb diet ..still on Glucophage and reducing insulin down to only 10 units per day ( from 20 ) However I have my life and productivity back .Hope Diabetes educators around the world will finally realise their guidelines have been wrong for years …

    1. Franziska Spritzler says:

      Thanks so much, Alison! Congratulations on the health improvements and reducing your insulin dosage by 50%! I’m so happy for you. Keep up the great work!

  5. Thanks for shedding light on another timely topic.

    1. Franziska Spritzler says:

      Thank you, Gerri!

  6. Eddie Mitchell says:

    Great post as always. For what my opinion is worth, all type two diabetes medications are best avoided, with the exception of Metformin. So many type two drugs have been found to be highly dangerous such as Actos and Avandia, to name but two. Most are useless in reducing BG numbers by any appreciable amount and all carry side effects, some very serious.

    Some time ago one of our team (Graham) found some information stating over two hundred type two meds were in various stages of development. Clearly big pharma can hear the cash registers ringing, but at what cost to the diabetic, financially and in complications.

    Intensive lowering of blood glucose numbers using multiple type two meds was tried in the ACCORD study and was a disaster and the trial was halted early, due to excessive deaths. What amazes me is the fact many healthcare professionals say that for many type two diabetics lifestyle is a major factor, but so few use a change of lifestyle to reverse the situation.

    As the very bright Dr. Jason Fung says, for many type two diabetics, insulin and medication only makes the situation worse. We need to reduce insulin resistance to reverse type two diabetes, treating the symptom of high BG numbers ain’t no cure and is never going to work long term.

    Within your blog all the answers for reversing type two diabetes are easily found, whole fresh food, moderate exercise, and of course, a strict reduction in starch, sugar and highly refined carbohydrates. For so many type two diabetics, medication should be the last resort, on the way to reversing their diabetes and living a long and active life.

    Good luck and health to you and yours.

    Kind regards Eddie

    1. Franziska Spritzler says:

      Thanks so much for your kind words and sharing great information. The risks associated with the majority of diabetes medications are indeed troubling. I agree completely that lifestyle changes (i.e. carb restriction, moderate rather than excessive fat and protein intake, and some form of exercise) trump pharmacological management of diabetes. Another benefit of a well-balanced, carb-controlled diet I didn’t mention is increased energy, and there are many others as well. Thanks as always for your continued support. Give my best to Jan.

      Franziska

  7. Hello Franziska,
    I actually wrote on one of your blogs a while back so some of this is repeated but I recently got some results that you might find interesting. I am not diabetic and never have been but I think you will see the relevance.

    Fourteen years ago I had a heart attack at 40 years old. I was overweight but very physically active. I was given the classic spiel about a heart healthy diet and then went gung ho and I started the Ornish diet (ultra low-fat mostly vegan) immediately and stuck with it for years. At 5’ 11” I went from 237 lbs. to 160 lbs. in about 5 months. I stayed right about 165 lbs. for over 7 years and remained very physically active. There is no question that you can, if motivated, lose weight on a low fat near vegan diet. But through the years I became complacent and honestly the blood pressure, cholesterol stats, and one type of test used by my cardiologist were not good and I have been on various medications for all this time.

    And frankly we felt deprived.

    My wife and I still tried to be careful to eat as low a fat diet as possible but we both slowly worked up to about 20 lbs. over weight no matter what we did. And it was boring and we always felt deprived.

    A little over a year ago we went low carb high fat even though it went against everything the heart health community has to say. It was such an about face from what we had done before. As the cook in the family, I found great recipes online and found ways to adjust many of the recipes that I had always used (daikon and carrots in pot roast instead of potatoes, for example). My wife and I both dropped the 20 lbs. we wanted within about three months. We could tell that it was all fat.

    My cardiologist does a type of stress test called a “cardiolite”. It is not like the ones they usually do. You are first injected with a radioactive material and then they put you in a scanner kind of like an MRI machine. They scan for 14 minutes then put you on a treadmill until you get to a certain heart rate, then inject you again with the radioactive material. Then, of course they scan you again for fourteen minutes. It is apparently the only accurate way to see how much blood is actually getting to the heart muscle. I have had to do these a number of times since I had an angiogram and stent placed in my artery fourteen years ago. The first one was a year after the heart attack. My cardiologist immediately put me back in the hospital for a second angiogram/catheter.

    The results of the angio showed that the lack of blood flow to the heart muscle was not a major blockage but instead was caused by the blockage of the capillaries that feed the blood actually into the heart muscle. Not a good thing but not something that the cardiologist could do anything about. Since then, every cardiolite has shown the same thing…….to the point where my cardiologist would say that he really should do another angiogram but then he would decide he could probably not do anything about the damage anyway. He did, however, keep me on a very short leash…..appointments every three months (for most people the appointments are every six months).
    .

    After being LCHF for a year, I just had another cardiolite stress test and lab work. The cardiologist said that the labs were excellent. My total cholesterol was slightly high……but only because my HDL was over the moon. Then he got to the cardiolite results. I had been living in fear that he would be sending me to the hospital again. I almost postponed the appointment because of that. Then he said “the cardiolite results are excellent.” All I could think was “wow one year to reverse heart disease.” All those years of low-fat vegan deprivation did nothing but that is how powerful LCHF truly is.

    There are two paths you can go by to lose weight and maintain a healthy weight, but only one is the way we evolved to eat. We did not evolve to be grain and fruit eaters.

    Keep up the good work.
    Rick

    1. Franziska Spritzler says:

      Hi Rick,

      I’m so sorry — I wasn’t alerted that your comment was pending and only found it by checking manually. Thanks so much for sharing your story, culminating in the fantastic cardiovascular improvement you experienced with LCHF! Truly remarkable and inspiring. Keep up the great work too!

      Franziska

  8. I adopted a ketogenic lifestyle over a year ago, initially to lose weight, but have now learned about the myriad of health benefits beyond weight loss. One of the most shocking things I learned is that the ADA still promotes a high carb diet, along with lots of insulin and other medications. To me, a fairly new keto person, it seemed obvious that diabetics should eat a low carb diet and that you wouldn’t need so much insulin if you didn’t eat so many carbs.

    We were recently discussing the benefits of keto and someone asked my youngest son’s girlfriend what her sister, a newly minted dietitian, thought about nutrition. Her answer was “everything in moderation”. Sigh. We all know how that doesn’t work for a lot of people and isn’t healthy in general.

    1. Franziska Spritzler says:

      Hi Lorraine,

      I apologize for not publishing your comment sooner, but I wasn’t alerted that it was pending. Thanks very much for sharing your story. The ADA is actually moving forward in accepting carb restriction as an option, which is encouraging. But yes, most dietitians do promote an “all foods fit” philosophy.

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