November is Diabetes Awareness Month and one of the most popular discussions this time of year is food, the relevance of which to this article will become apparent shortly. We wanted to address perhaps one of the most important distinctions that should be made in the context of diabetes: the difference between nutritional ketosis and diabetic ketoacidosis; one being a natural, healthy response to a very low carbohydrate diet and the other being a life-threatening condition seen in uncontrolled type 1 diabetes.

What are ketones?

Ketones, or ketone bodies, are molecules that are produced from the breakdown of fats in the liver. These are then transported in the blood and act as efficient energy sources for the body’s cells, especially in the brain.

Our body produces three different ketones: beta-hydroxybutyrate (BHB), acetoacetate (AcAc) and acetone. BHB is the main ketone produced and is what is measured with a blood ketone test, the most accurate way of measuring ketones. AcAc is measured by urine sticks and acetone is measured by ketone breathalysers, but these methods are less accurate and informative than blood testing.

Everyone produces a low level of ketones under normal conditions and has a low level (under 0.5 mmol/L) in the blood at any given time.

What is nutritional ketosis?

Every person is burning at least some fat for energy, which is why low levels of ketones are always being produced. When dietary carbohydrate is greatly reduced, down to around 20-50g per day, the body adapts to this lack of carbohydrate energy by increasing its burning of fat. Therefore, higher levels of ketones are produced in the liver and blood ketones rise (to around 0.5 – 3.0 mmol/L), placing the body in a state known as ‘nutritional ketosis’.

A very low carb diet which results in nutritional ketosis is therefore called a ketogenic diet. Outside of type 1 diabetes, the body regulates this level of ketones in multiple ways and prevents them from rising too high. A ketogenic diet can be used for both weight loss and weight maintenance because the fat being burned can come from either the diet or the body’s own fat stores. A ketogenic diet that does not aim to shed a large amount of weight is therefore usually high in fat.

It can take some time, often two weeks or more, before the body becomes fully adapted to making proper use of this higher level of ketones. During the first week or two, some people may experience side effects such as low energy, dizziness and muscle cramps. This is sometimes referred to as ‘keto flu’.

After the body is properly adapted, nutritional ketosis is considered to give a significant metabolic health benefit. Because of this, ketogenic diets have applications in weight management, general health and wellbeing, athletic performance and in the treatment or management of various metabolic diseases, such as type 2 diabetes, Alzheimer’s disease, epilepsy and some cancers.

What is diabetic ketoacidosis (DKA)?

In contrast to nutritional ketosis, DKA is a very different ball game. This is a very dangerous, potentially life-threatening condition. DKA occurs in people with type 1 diabetes who have not taken enough insulin. This includes people with undiagnosed type 1 diabetes, predominantly children, who have not received insulin.

DKA develops when ketone levels are around ten times the levels seen in nutritional ketosis. Dangerously high levels of ketones make the blood acidic, resulting in tiredness, dizziness, nausea, extreme thirst, breathlessness and eventually coma and death if left untreated. Symptoms of DKA usually develop over the course of a day, but can come on faster.

The cause of DKA is subtly, yet importantly different from the mechanism behind nutritional ketosis. When a person with type 1 diabetes has not taken enough insulin, the body enters a state of ‘internal starvation’. This is when there are high levels of glucose in the blood, but no way to get this glucose into the cells to use for energy, so the body believes that it is starving. In order to make more energy available, the body begins to rapidly break down fat into ketones in an emergency fashio, causing ketone levels to shoot up far above those seen in nutritional ketosis. This emergency breakdown of fat is also why rapid, unhealthy weight loss is seen in uncontrolled type 1 diabetes.

It is recommended by the NHS  for people with type 1 diabetes to check their ketone levels, either with a blood test or urine test, if the blood glucose level is over 11 mmol/L. Increased ketone levels alongside high blood glucose levels indicate an increased risk of DKA. In addition, ‘fruity’ breath is a sign of DKA since high levels of acetone are expelled by the breath in this situation.

Outside of type 1 diabetes, there have been rare occurrences of ‘euglycemic ketoacidosis’ in people with type 2 diabetes taking SGLT2 inhibitor drugs, also known as gliflozins. This means that it is possible for ketoacidosis to occur alongside normal blood glucose levels with use of these drugs.

The take-home message

Ketones are, at physiological levels up to around 3.0 mmol/L, efficient energy sources for the body that may provide a metabolic benefit in many situations. These levels of ketones are produced during nutritional ketosis, which usually occurs when restricting carbohydrates down to around 20-50g per day, with or without high amounts of dietary fat.

DKA occurs in people with type 1 diabetes with a relative lack of insulin, causing a situation of internal starvation and much higher levels of ketones that are damaging to the body. This life-threatening condition should not be confused with nutritional ketosis.

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