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

    18 January 2017

    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.