Ketosis and ketoacidosis

National Botanic Garden of Wales, May 2013

When I was visiting Mr M and Lola II recently, Mr M and I had a brief discussion about ketones which made me think harder about exactly what happens when carbohydrate is restricted in ketogenic diets. Here is what I think.

Without diabetes

The body's fuel of preference is glucose, and its main source is from the digestion of carbohydrate foods which delivers glucose into the blood. Insulin is secreted from the pancreas in response to rising blood glucose, so when carbohydrate is plentiful and blood glucose levels are high, levels of insulin in the blood are also high. Insulin has a number of functions in the body, two of which are facilitating the uptake of glucose from the blood into cells so that it can be used as fuel or stored as glycogen or fat, and also preventing the breakdown of glycogen or fat in the liver and adipose tissue. It makes sense: if you've got fuel coming into the system from food, there's no need to retrieve fuel from stores.

In a non-diabetic person, in the absence of dietary carbohydrate the blood glucose is low, consequently insulin levels are low, and the inhibiting effect of insulin on the liver is reduced. The liver sends its stores of glucose into the blood and just enough insulin is secreted to allow uptake by cells to use for energy. When liver stores of glycogen start to run out, fat starts to be broken down for fuel. One of the byproducts of burning fat is the production of 'ketone bodies' or 'ketones', which are used for energy in a metabolic state known as 'ketosis'. This is entirely normal, especially when someone is deliberately trying to lose weight, and is variously called 'physiological ketosis', 'dietary ketosis' or 'starvation ketosis'.

In this situation, low levels of ketones are detectable in the blood and urine, and blood glucose and insulin levels remain at the low end of normal. If the level of blood ketones rises then insulin production is triggered, which halts the breakdown of fat and the formation of ketones. Through this feedback loop the level of ketones is kept within normal physiological limits while at the same time the body is supplied with sufficient fuel for its needs.

Type 1 diabetes

The word 'ketone' is a danger signal for people with Type 1 diabetes, because they are taught to test for ketones when blood glucose is high. A high level of blood ketones can be life-threatening, but this is because of ketoacidosis rather than ketosis.

In Type 1 diabetes it is possible for the level of insulin in the blood to be insufficient irrespective of the level of blood glucose. This could be because insulin has not been injected, or the insulin has been denatured or spoiled, or because of illness*, or for a number of other reasons. If insulin is lacking then glucose remains in the blood and cannot be taken up by the cells of the body, which mimics a state of starvation. So the liver starts to break down glycogen and fat to be used for energy, increasing the level of useless blood glucose and leading to the production of ketone bodies. Because this can only happen if you have Type 1 diabetes (or a very advanced stage of Type 2 Diabetes where the pancreas cannot produce any insulin), it differs from 'physiological ketosis' and is called 'diabetic ketosis'. The way to tell the difference is that with physiological ketosis blood glucose levels are low, but in diabetic ketosis blood glucose is high.

Ketone bodies are acidic, so in prolonged diabetic ketosis the blood becomes more and more acidic, which is definitely a bad thing. Because insulin is missing, the feedback loop to keep ketones within physiological limits doesn't work. Unless sufficient insulin is given, diabetic ketosis progresses fairly quickly to diabetic ketoacidosis, or DKA. DKA is what people with diabetes used to die from before insulin was discovered and isolated. People with Type 1 diabetes receive grim warnings that if they detect blood or urinary ketones above a certain level and are unable to reduce their blood glucose by injecting insulin, then they are to waste no time in getting to a hospital emergency department, especially if they have stomach pain or vomiting.

Ketogenic diets

This type of diet severely restricts the intake of carbohydrates in order to induce physiological ketosis. Ketogenic diets have come in and out of fashion, having been used to treat epilepsy since the 1920's, and rising in popularity more recently in the form of the Atkins diet. The current evidence suggests that they are safe, don't increase risk of cardiovascular problems as long as the type of fat is predominantly unsaturated, and seem to be an effective route to weight loss although it is not really known exactly why. A ketogenic diet is increasingly popular in improving glycaemic control in people with Type 2 diabetes, and can also be useful in Type 1 diabetes but needs to be very carefully managed so as not to result in DKA.

This is the basis for the very low carbohydrate diets that we promote to our patients. I have had little luck in 'selling' them to my patients so far, so in an attempt to become more familiar with the practical aspects I am planning to adopt a very low carb diet myself. I will be starting after the weekend, and probably ending after about three weeks when we go away on holiday. I will let you know how it goes!

* Illness completely messes up glucose metabolism in Type 1 diabetes in a way that I am not confident to write about yet.

ED

Monastery in Melk, October 2012

There's not much I can write about on this blog, due to my self-imposed rules of not breaching patient confidentiality and trying not to write anything that isn't positive and constructive. That's why I am so delighted when something happens at work that I can write about.

In the diabetes department we have quite a few lunchtime educational talks, often from reps trying to sell something. Doctors, Diabetes Specialist Nurses, Therapy Assistants and Dietitians all attend on an irregular basis - there is no compulsion, but the lunches are often attractive. This week, a talk was advertised entitled 'ED and lifestyle'.

Eating Disorders afflict people with diabetes in the same way as in the general population, but Type 1 Diabetes brings with it the 'opportunity' for weight loss by under-dosing insulin or omitting injections. Glucose from dietary carbohydrate enters the bloodstream after digestion, but without insulin it cannot leave the bloodstream to be used for energy or stored as fat. The level of blood glucose increases, and when the renal threshold is exceeded, it is excreted by the kidneys into the urine. Incidentally, this is how diabetes used to be diagnosed before insulin treatment was available - the urine tastes sweet because of the glucose in it. So by ensuring that there is little or no insulin about, calories in food are disposed of before they can cause any weight gain.

The drawback of this strategy is ketoacidosis. If glucose is unavailable as a source of energy because of a lack of insulin, then fat is burned instead, resulting in the production of ketones, which are toxic. If ketones accumulate in the blood then the blood becomes acidic, and this is called Diabetic Ketoacidosis (DKA), which is a very nasty condition, and can be life-threatening. It is what diabetics used to die of before insulin therapy was invented. In addition, maintaining the kind of high blood sugars that are necessary to achieve this metabolic state greatly increases the likelihood of complications such as blindness, kidney failure and nerve damage.

The practice of under-dosing insulin and continuously hovering on the brink of ketoacidosis has been termed 'diabulimia', and it has been proposed in some quarters that it should be formally recognised as an eating disorder associated with diabetes. So when RSB and I found out that there was to be a talk on ED and lifestyle, we thought it would be really interesting, and very relevant to our work. Unfortunately, another meeting about student placements that we really had to attend had been scheduled at the same time.

Nobly, RSB volunteered to go to the student placement meeting while I attended the ED talk. The room filled up, and the speaker started with some slides about how inactive the UK population had become, and how this is contributing to the obesity epidemic. Nothing new for me here, but I wondered what the relevance was to Eating Disorders. I also wondered why so many doctors had turned up, because they are busy people and I didn't think that the topic would be a priority for them.

Two minutes later I quietly slipped out of the room, and went on to the student meeting, which had pretty much finished. RSB filled me in on what had happened there, and asked what I had learned in the ED lecture.

"You thought the same as I did, didn't you, that ED stood for Eating Disorders" I said.

"Yes," he replied, "Doesn't it?"

"Ah," I said. "No. It turns out that ED doesn't stand for Eating Disorders where diabetes is concerned."

"Oh." He thought for a moment. "What does it stand for, then?"

"Erectile Dysfunction."

Once he had finished laughing, he amused me further by telling me that he had met the speaker just before the talk, and apologised that he wouldn't be able to stay, but said that we were very interested in ED and lifestyle and I would be there and would feed back to him, and we could take the speaker's contact details if we needed to follow up later. On reflection, I don't think we will.

Ketones

Brixham harbour, August 2012

Warning to readers: more of the technical diabetes stuff coming up.

I do try to simplify the descriptions and explanations of what I'm learning about diabetes. Firstly because I want people to be able to understand what I write, and secondly because it's good to practise what I would say when there's a patient in front of me. I want them to be able to understand the information I provide, and it helps to think about it in the writing of this blog.

So this post is about what happens when things don't go quite right with diabetes. 'Ketones' are a by-product of fat metabolism, i.e. when fat rather than carbohydrate is used to generate energy, a state known as 'ketosis'. The main reasons why this would happen are a) if less carbohydrate is eaten than the body needs for fuel, which might be if someone is deliberately trying to lose weight or is on a low-carb diet, or b) if there is a lack of insulin, in which case the blood glucose just can't get into the cells to fuel carbohydrate metabolism. The two types are sometimes respectively called 'starvation ketones' and 'diabetic ketones'.

Starvation ketones don't generally build up to significant levels, and aren't a problem. Diabetic ketones, on the other hand, are an indication that all is not well.

Diabetic ketones arise when there is a deficiency or lack of insulin in relation to blood glucose. The most common scenarios are either when a person with Type 1 diabetes stops injecting insulin for one reason or another, or when they get ill, which tends to result in higher blood glucose levels. If this glucose isn't available to be used for energy - if it can't get out of the bloodstream into the cells due to the lack of insulin - it will hang around in the blood, keeping levels high, and be excreted in the urine, potentially causing dehydration.

Because the body isn't aware that the reason for lack of carbohydrate fuel is that it's all in the blood and not in the cells, this will provoke the breakdown of fat, leading to a rise in blood ketone levels. In people with Type 2 diabetes who are still producing endogenous insulin, the presence of the insulin inhibits fat breakdown, which produces a protective effect, so Type 2's generally don't become ketotic. But their livers will keep chucking more glucose into the blood, not realising that there's plenty there already, keeping blood glucose levels high as can be.

Ketones in excess are damaging to the body because they are acidic, and acidic blood is not a good thing. The body responds to raised ketones by excreting them in the urine, but also via the lungs, which is what causes ketotic diabetics and slimmers on the Atkins diet to have breath that smells of pear drops or nail varnish remover. Historically, ketones were measured in the urine, which gives an indication of ketone levels over the period that the urine has been accumulating in the bladder. It is now more routinely possible to measure blood ketones, which are a more immediate indication of the current situation.

Raised ketones with normal blood glucose suggests starvation ketones - a lack of carbohydrate - and is not immediately worrying. Raised ketones with raised blood glucose is an indication of diabetic ketosis, and depending on the level of ketones, an individual may just monitor the situation, inject extra insulin, or take themselves to the Emergency Department of the nearest hospital. If ketosis has progressed so that the blood is acidic (known as diabetic ketoacidosis or DKA), it is usually necessary to start medical intervention, often with an IV infusion of insulin. If the illness (or the DKA) has caused vomiting and dehydration as well, then glucose and re-hydration will probably be needed too. It's a life-threatening condition if left untreated.

As well as illness, there are potentially many other causes of DKA resulting from disruption to the delivery of insulin: faulty insulin pumps, blocked or kinked cannulas, bubbles in pump tubing, forgetting or neglecting to give injections, hitting 'lipohypertrophy' when injecting so the insulin is poorly absorbed, insulin that is out of date or has been inactivated through heat or cold, being an inpatient or unconscious and not being given insulin, and there are probably more reasons that I haven't immediately called to mind.

In contrast with these unintentional insulin deficiencies, 'diabulimia' is the informal name given to a type of behaviour that involves injecting less insulin than is needed, in order to excrete glucose instead of utilising it, and thereby remaining both slim and constantly on the brink of DKA.

Within all the education and empowerment and interaction we have with diabetic patients, especially those with Type 1 diabetes, 'Never Stop Taking Insulin' is probably the most important central message that we offer.