Does the drug that ‘fixed’ my diabetes have a dark side?

A while back, I wrote about how dapagliflozin revolutionised my glucose control. Almost overnight, I changed from a morbid and morbidly obese failing diabetic to a nearly new fifty-something with a rejuvenated lust for life. My HbA1c returned to normal levels and my retinopathy disappeared. I was advised to stop taking gliclazide as my glucose control seemed to be perfect, and I didn’t want to experience hypoglycaemia. I even stopped pricking my finger to measure my blood sugar. I felt my diabetes was behind me.

I had also discovered a low-carb diet I could live with: bacon and eggs, kebabs, lamb chops and steaks with mustard, hummus and delicious cheeses, all accompanied by lots of salads in mayonnaise, and non-starchy veggies. Yumm! I lost three stone effortlessly. It became embarrassing how many people remarked on how well I looked, having been a sickly fat blighter for all the time before.

I felt strong enough to take on a big project helping to plan and implement the regeneration of healthcare in my very rural locale. It involved lots of travelling to meet the public and speak frankly to them while thinking on my feet. I attended endless meetings and video conferences where I had to learn the tiresome new lingo of management-speak. All of this was done alongside my day and night job as a resident consultant in intensive care and anaesthesia.

Before even six months were up, I began to feel a bit flakey. My memory and concentration were not good. I was having difficulty keeping up with the meetings. I was prone to emotional lability, most noticeably at home, and, most worrying of all, I was drinking too much alcohol to get to sleep. And then I noticed the smells of scrumpy and pear drops in my breath, sweat and urine. Not everyone can detect these smells. My blood sugars, when I measured them, puzzlingly remained normal.

With what little wits remained to me, I suspected that my cellular metabolism had switched over to ketosis from glycolysis. This is the body’s survival mechanism when faced by starvation. Cells stop relying on glucose, which is no longer incoming, and start burning stored fats and amino acids instead. These produce ketones which can be utilised as an energy source by the brain and heart especially, but also by any cells with mitochondria, which is all of them except red blood cells.

My cells were all starving for glucose, as my own insulin levels were inadequate to allow them to take it up, and so they were involuntarily enduring a permanent black fast. Ketones are the only energy source at such times, and their levels were soaring such that my breath, sweat and urine smelt like my wife’s nail polish remover. At that time I had no means at home to measure my ketone levels. I didn’t have breathlessness or other worrying symptoms. I just felt a bit under the weather. I decided to ignore it and soldier on.

However, one night, after a particularly prolonged and stressful clinical encounter, I came over all faint and unsteady, and quite frankly a little bit trippy. Perhaps I was hypoglycaemic — I had foolishly gone to work without my supper. My blood glucose was normal though. I got a urine dipstick from the ward cupboard and used it. The little ketone square turned very dark. Result! At last I had hard evidence of what the heck was going on with me: I was in fact severely ketotic.

It was an epiphany of sorts: everything suddenly fell into place. I was weak, dysfunctional and spaced out for a reason. I spoke to my second on-call colleague who agreed he would come in to cover me if needed. As it happened, the rest of the shift was quiet and uneventful. After several large mugs of sweet tea, some food and a lie down, I felt back to normal. I stayed at my post.

The next morning, I contacted my GP and occupational health to request a leave of absence. I resigned from my taxing extra commitments, and got kitted out with a blood ketone meter. I was restarted on a low dose of gliclazide, which acts by stimulating my failing pancreas to release more insulin. I asked to be kept on dapagliflozin, as I had such faith in its ability to control my blood glucose. I promised my doctor that I would from now on be ever vigilant about ketosis, especially if unwell or stressed. With a little rest and recreation, things quickly resolved, and I soon returned to work much the wiser.

When one’s brain is running on ketones, it doesn’t think straight. It is like being continuously tipsy, and therefore somewhat disinhibited, and perhaps a little loopy at times. I now see why fasting is so important to the religious as it helps them escape virtuously to the higher realm.

Around this period, my intensive care unit started admitting a large number of patients of all ages suffering from ketotic coma — that is, their ketosis was so severe that they had become unconscious and required urgent medical care. What was unusual, apart from the increased number, was that all of them were type-2 diabetics taking dapagliflozin, and they all had normal blood glucose levels. They rapidly responded to insulin and fluids, recovered, and were discharged. The medical literature at the time reported that this phenomenon was being noticed all around the world.

There is a theory that this new drug is causing these patients to go into ketosis, perhaps by stimulating glucagon or other hormones that increase the body’s needs for insulin, but evidence for this is not there yet. At the risk of being labelled a heretic, I offer a different explanation.

Dapagliflozin provides such excellent glucose control that diabetics become blasé about their condition, as I did, and thus sink unwittingly into ketotic coma when stressed, or unwell, or even after a few drinks, though their blood sugars remain well controlled. This almost happened to me. Ketosis creeps up on one. It can be a silent killer. The best solution is to always be on the lookout for it.

Here is an interesting American case series from 2015, about euglycaemic diabetic ketoacidosis, for those who want to read deeper.

Your comments are welcome, dear readers.

  • Sara

    Surely have a dark side. I was diagnosed with type 2 Diabetes and put on Metformin on June 26th, 2016. I started the ADA diet and followed it 100% for a few weeks and could not get my blood sugar to go below 140. Finally i began to panic and called my doctor, he told me to get used to it. He said I would be on metformin my whole life and eventually insulin. At that point i knew something wasn’t right and began to do a lot of research. On August 13th I found Lisa’s diabetes story (google ” HOW EVER I FREED MYSELF FROM THE DIABETES ” ) I read that article from end to end because everything the writer was saying made absolute sense. I started the diet that day and the next morning my blood sugar was down to 100 and now i have a fasting blood sugar between Mid 70’s and the 80’s. My doctor took me off the metformin after just three week of being on this lifestyle change. I have lost over 30 pounds and 6+ inches around my waist in a month. The truth is we can get off the drugs and help myself by trying natural methods

    • Sara , may you enjoy good health & a long life

    • Borg-Again Cyber-Atheist

      Your comment sounds like an advert for Dr Max Sidorov. He peddles books about curing diabetes through diet. They might be a heap of huey, but my bloodthirsty anti-human atheist blessing is upon him because worthless untrue crap is our “solution” to all the world’s “problems”, hehehe.

    • FairlyOldGit

      I smell a nasty rat with this comment – during a Google search it has
      appeared over and over again, with exactly the same phrasing …”I read
      that article from end to end. . . .” Jan 2017, Feb 2017, April 2017, May
      2017 etc. etc.

      I haven’t been able to locate Lisa’s M – it seems that it is all an
      American con trick trying to to sell you something.

      The whole comment should perhaps best be ignored !

  • Dr. Campbell, Wishing you good health & long life

  • davidofkent

    Unfortunately, the people who should read all about diabetes never read anything at all.

    • MiddlelandExile

      A rather sweeping statement. Since the BBC can’t use the words “Type 2 diabetes” without appending the words “..which is associated with obesity”, you’ve obviously bought the theory that the disease is a lifestyle choice. For some, that may be the case. When I was diagnosed, I read widely on the subject – and the ‘official’ advice, from the likes of Diabetes UK and others, was to base one’s diet on carbohydrates. I have found that the only way I can keep some sort of control over my blood glucose is to regard carbs as the enemy. Perhaps it’s our modern diet which is driving the incidence of diabetes?

      • Its hard to determine if its our modern diet which is driving the incidence of diabetes, our ancestors ate fresher & less processed food but still died young & suffered from disease and infection.

        • Enoch Powell

          Died mostly from viruses and bacteria against which we had little protection before the age of modern medicine. I think its very clear that modern food plays a part in the diabetes epidemic, at least in the west. Overeating carbs certainly plays a part, we are omnivores and protein and veg should be the largest part of our diet, not Greggs and Chips. Finally Obesity certainly does play a part in reinforcing the problems of diabetes, but it is also a major symptom of diabetes, especially undiagnosed. As is overeating, the less your body metabolises sugar, the more you crave it.

          • I am fortunate in not having diabetes . An uncle of mine had it, was on medication for most of his adult life and lived to a ripe old age of 90 before dying a few months after a bad fall at home in which he broke an arm & some ribs . He was hospitalized , discharged & cared for by his children but never recovered his strength & faded away.
            I agree that we must be careful what we eat especially sugar laden foods, ditto for all processed / preserved foods full of salt & chemicals

          • Polidorisghostfriend

            Surely if he lived to 90 it didn’t matter? We all have to die of something. My grandad just died, he would have been 92 in May. There are no regrets and I’m glad for every mouth of tasty delight he ever ate.

      • davidofkent

        I believe that it is mostly a lifestyle choice, but there are certainly exceptions. My brother-in-law has always been as thin as a rake but he was diagnosed Type 2 Diabetic a few years ago. OTOH, he has always loved his cream buns.

        BTW, it’s the refined carbohydrates which do the damage.

        • Polidorisghostfriend

          Yes, but it’s the refined carbs that memorable meals are usually made of. I’m a pastry cook, myself. We love ’em for a reason. Then again, I can do a two-minute plank and chaturanga in robust vinyasa, so I know how to compensate for my indulgences.

    • Enoch Powell

      I was diagnosed as type 2 diabetes 3 years ago.

      I was given lots of literature to read and read absolutely none of it.

      This was because I was misdiagnosed and was actually a type 1 diabetic who had been given the wrong medication. I was barely capable of standing up, let alone reading. I was on metformin for three years and survived being ketotic for at least 6 months before I was finally referred to hospital, properly diagnosed and put on insulin.

  • King Zog

    Is this thing used for Type 1, which I have?

    • Enoch Powell

      The only medication for type 1 is Insulin. Type 1 is an autoimmune problem where your body produces antibodies to stop your pancreas producing insulin. Mine was slow onset and I was misdiagnosed as type 2. I was on metformin which worked a little bit, for a while until my body stopped producing insulin at all, at which point I nearly died. I was also on Gliclazide for a little bit and stopped taking it as it kept giving me hypos. No drug can cure or mitigate type 1. Type 2 is different and is when your body has trouble using insulin. Drugs can help there. I have seen that there is progress being made in possible gene therapy solutions.

  • Dr Brian Campbell

    Thanks for the comments folks. I shall try to address all your points and questions.

    A low carb diet/fast is absolutely fine for non-diabetics and those who are not taking metformin. That drug prevents the liver from making glucose from amino acids, glycerol and other sources. In its presence, the body rapidly switches over to ketones which cause the brain to misfire, which is great at low doses, but leads to confusion and coma as the levels increase. Ketones appear to facilitate the inhibitory pathways in the brain. Here is an interesting link from Scientific American that may explain it better:

    Non-diabetics always have plenty of insulin available to meet their metabolic control requirements. Their cells are never subject to severe glucose starvation even when they go on a low carb diet.

    My article neglected to mention that I am also taking metformin. Thus, when deprived of glucose/carbs, I quickly switch over to ketone metabolism and thus get into trouble.

    Dapagliflozin can be prescribed for type 1 diabetics but this use is off-label and is thus the responsibility of the prescriber and patient together. It can lead to reduced insulin requirements and weight loss.

    The take-home message of my article is this: Diabetic keto-acidosis is the inevitable result of one’s body lacking sufficient insulin. Good sugar control, while great, is not the whole story. Ketones can kill. Keep an eye on them!

    I will check back to see if I haven’t been abundantly clear 😉