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.