Many parents are frightened of ketocidosis – a condition triggered by lack of insulin. Those who know how the body reacts to insulin shortages can recognize the early symptoms and act accordingly should this occur in their children. 

Some readers will recall the images of their severely ill child with ketoacidosis at the time, for example, when the diabetes was first diagnosed. Other situations involving a lack of insulin can bring forth an attack of ketoacidosis such as infection, or when the insulin dosage is set too low over a certain period of time.  

What is ketoacidosis?
Ketoacidosis is a type of metabolic acidosis which occurs when too much sugar is present in the blood (over 200 mg/dl, or 11.1 mmol/l). This causes it to become highly acidic (pH value under 7.3, or bicarbonate level of under 15 mmol/l). This metabolic disturbance (dysregulation) is manifested by high glucose readings and ketones in the urine.

Ketones are produced by the breakdown of fat. The presence of excess ketones in the blood leads to further metabolic imbalances such as salt and water depletion. Dehydration results, and energy levels drop.

Insulin is responsible for the transport of glucose (energy) to the cells. If there is not enough insulin, the muscles fail to receive sufficient energy. When this happens, the fat stores are broken down (lipolysis) for the muscle cells to use as a so-called ‘emergency’ energy supply. This process releases free fatty acids into the bloodstream.

As insulin inhibits the breakdown of proteins, a lack of insulin results in the increased degradation of protein in the muscle cells, for which the breakdown products (amino acids) needed in this process are made available.

Energy from Fatty Acids
In the case of an insulin shortage, the fat cells fail to produce fat. The reason: The elements available for this purpose, such as fatty acids and glycerol, cannot be catabolized. As a consequence, fatty acids are taken from the fatty tissue and either converted to energy by the mitochondria in the cells, or further metabolized into ketone bodies. This creates a metabolic ‘catch-22’ situation. Excess amounts of ketone bodies are released, but cannot be broken down. They overflow into the blood and the urine.  
 
Increased Blood Acidity
The emergency measures taken by the body in the presence of an insulin shortage have one disadvantage: acidic by-products, such as ketone bodies, are released into the bloodstream and change its normal chemical balance. The pH of the blood plummets. One of the ways the body tries to rid itself of the acidic by-products is by exhaling them via the lungs. This results in a gasping type of breathing (‘Kussmaul’ breathing, named after the doctor Adolf Kussmaul), which has a characteristic acetonic or fruity smell.  

More Glucose from the Liver
In the absence of insulin, more glucose is released from the liver – a process that sufficient amounts of insulin would normally hinder. This serves to double the hyperglycaemic effect. In other words, not only does the initial lack of insulin prevent the glucose from being taken up in the cells and utilized as energy, causing a build-up of glucose in the blood, but the liver starts producing more glucose!  

Dehydration of the Cells
An insulin shortage also depletes the body’s salt and water content. When sufficient insulin is present, the same amount of glucose can be found in the cells as well as between the cells. When insufficient insulin is present, there is an elevation in the level of extracellular glucose. The surrounding cells secrete water into the bloodstream in an effort to lower the glucose level to that of within the cells. The body trys, in vain, to retain its internal equilibrium. However, this action only serves to deplete the cells of moisture. Among other factors, the addition of water into the bloodstream drastically disturbs the body’s elecrolyte balance, significantly hindering the normal function of all cells, especially the brain cells.  

Natural Protection of Brain Cells
Individual brain cells have an in-built protective factor against such water imbalances to some extent. However, once this defence is depleted, due to the severity of the metabolic dysregulation, it can lead to restlessness, irritability, confusion and loss of consciousness, and sometimes even coma.

Excess Renal Secretion
The kidneys filter the blood. If blood glucose levels rise to in excess of 140 mg/dl (7.8 mmol/l), however, glucose is released in the urine, taking with it water and salt—water that would normally be ‘recycled’ and taken up again by the body. Consequently, the body dehydrates even further. The symptoms: intense thirst and frequent urination.

Children more Susceptible
At the outset of diabetes, ketoacidosis occurs rather frequently – in up to 30% of patients. It occurs more often in children, but is usually not threatening. The more aware the parents or carers are of this condition, the higher the chance that the tell-tail signs will be quickly recognized, and the condition nipped in the bud before a significant metabolic imbalance takes hold.

The risk of ketoacidosis in diagnosed diabetes is 1:100/year. Those most at risk are children with poor metabolic control and a high HbA1c value, as well as a tendency to ketosis (elevated levels of ketone bodies in the blood).

The actual mortality rate due to ketoacidosis lies somewhere between 0.46% and 0.87%. The cause of death is usually due to cerebral trauma caused by intracranial pressure (swelling of the brain) at the initiation of treatment with infusion. Only in very rare cases is death directly attributed to the diabetic coma itself, due to dehydration of the brain cells.

Recognizing the Signs
The symptoms of hyperglycaemia and dehydration are: frequent urination, increased thirst, weight loss, loss of energy, loss of concentration, fatigue, and weakness in the muscles. Later, one can recognize more specific signs of dehydration such as sunken eye sockets, dry lips, a dry, coated tongue, rapid and shallow pulse, low blood pressure, and clammy skin.

As already mentioned, the patient gasps for breath (Kussmaul breathing), experiences abdominal pain, nausea and vomiting through the presence of excess ketone bodies. (In such cases, appendicitis is often erroneously diagnosed). Once the brain is affected, the patient can lose consciousness, convulse, and potentially fall into a coma.

Intervention
Three steps are needed to treat ketoacidosis. They are:

1. rehydration – in order to restore the body’s water and mineral balance;
2. administration of insulin; and
3. the restoration of energy by the consumption of calories.

Experienced families usually manage to hinder the onset of ketoacidosis at home under the guidance of their diabetes centre. This is usually done by raising the dosage of insulin, offering more fluid, and rest. If the ketoacidosis has already set in, the child should be immediately admitted to the clinic. There, the paediatric team will order the necessary infusions and observe the metabolic parameters and vital signs in order to avoid the much-feared cerebral trauma that can occur at the initiation of treatment.

Preparational Courses
Many diabetes centres offer training courses in the prevention of ketoacidosis. This is especially important for those wearing a pump. If, for example, the catheter becomes blocked, and the flow of insulin is unknowingly interrupted, a sudden insulin shortage will take place. Ketoacidosis will immediately set in.
It is advised that, in such cases, two corrective boluses be administered. If this should fail to correct the high blood sugar levels, it is recommended that a pen or injection be used and, in any case, to replace the catheter. 

Emphasis is also placed on the need for frequent ketone measurements, and how this is done (for example, interpretation of urine test strips). Once the ketone levels are known, the amount of addition insulin can estimated with some accuracy. A rule of thumb: blood sugar levels over 300 mg/dl (16.7 mmol/l), and no raised ketones, will require an injection of around 10% of the normal total daily insulin dose. If the ketone test shows positive, the amount should be doubled.

Contrary to what some may think, it is very important to keep cool during hyperglycaemic episodes – as opposed to trying to ‘run’ the sugar level down – until the worst of it is over. Physical exertion during hyperglycaemia only serves to aggravate the ketoacidosis by accelerating the level of toxicity within the muslces.

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Claudia Nestoris MD
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