Type 1 Diabetes and Management of DKA
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  • Type I diabetes is a disorder that results from the destruction of the beta cells of the pancreas, which produce insulin
  • It accounts for about 10% of cases of diabetes mellitus, the other 90% are type 2 diabetes
  • It occurs in genetically susceptible individuals with environmental trigger factors, although the exact aetiology is not well understood
  • The development of the disease probably occurs over months or years, during which time, the patient is asymptomatic
  • It can cause the acute presentation diabetic ketoacidosis (DKA) which is life-threatening if untreated, although with the correct treatment, it often improves rapidly
  • Patients require life-long insulin therapy
  • The pathology differs from type 2 diabetes, where decreased insulin production, and increase insulin resistance in the peripheral tissues are the main factors


  • It is not strictly genetically determined, but a given individual may have an increased risk due to their genetic make-up. Monozygous twins show a concordance rate of 30-50%.
  • The risk is highest in those with a close family member with type 1 diabetes
  • Certain human leucocyte antigen (HLA) variants are correlated with the disease
  • Having a father with type 1 puts you at greater risk (3-8%)¬†than having a mother with type 1 diabetes (1-4%)
  • It is often associated with other autoimmune diseases, particularly auto-immune thyroid disease, celiac disease¬†and pernicious anaemia.
  • Proposed environmental triggers include viral infection, and early exposure to cow’s milk in childhood.¬†Particularly suspected are enteroviruses such as coxsackie, Epstein-Barr, rubella, mumps. It is thought that this risk is greatest if an individual was exposed wither very early in life, or before they were born, via the mother (in utero).
  • Also suspected but not proven is a ‚Äėclean environment‚Äô during childhood. This means less exposure to pathogens, and thus the immune system is not stimulated as much as normal in a child. This is known as the hygiene hypothesis and it is a hypothesis for all autoimmune diseases.
  • Bovine serum albumin (BSA) has also been implicated. This is found in cow‚Äôs milk. This link has been proposed because type 1 diabetes is more common in those who were not breast fed. BSA can cross the neonatal gut and enter the blood stream. Its structure is similar to a heat-shock protein that is expressed on the surface of beta cells, and thus the child may develop antibodies to BSA, which it is then suggested may cause an immune reaction against beta-cells.
  • Nitrousamides ‚Äď these are found in smoked and cured meats and some have also suggested these may be implicated.
  • Islet cell autoantibodies (ICAs) have been identified in up to 85% of individuals with type I diabetes, although it is likely there are several antibodies involved, including anti-insulin antibodies
    • Testing for antibodies can help to confirm the type of diabetes present (T1 vs T2)
    • Anti-insulin, anti-islet cell antibodies and GAD (glutamic acid decarboxylase) can all be tested
    • They are not totally specific. up to 10% of T2DM patients will show antibodies, and they are absent in about 10% of T1DM patients
    • If the diagnosis remains uncertain, consider referral to an endocrinologist


  • It is a disease that usually shows itself in childhood. There are two incidence peaks, one around age six, and one around the time of puberty (age 10-14).
  • Incidence shows strong geographical variation. In the USA, in white children, the incidence is about 15 per 100,000, and lower in children of other racial backgrounds
  • The incidence of type-1 diabetes is on the increase, particularly in children under 5. The annual increase in Europe is about 3-4%.
  • There is no gender difference in incidence, despite the fact that autoimmune diseases are usually more common in women


  • It is a T-cell mediated autoimmune disease that results in destruction of beta cells of the pancreas. It is quite slowly progressing. It can be caused by other pathologies, and so technically speaking the type caused by T-cell mediated autoimmunity is type 1A, however, the other causes are very rare.
  • High glucose levels, lead to high osmolality of blood, and thus the patient become ‚Äėdehydrated‚Äô and has to drink lots. They will also secret lots and lots of aldosterone.
  • Age of onset is typically around puberty.
  • Investigations have shown that the first islet antibodies appear in the blood during the first few years of life. This shows that the disease is very slow to progress, and also opens up the possibility of screening and prevention programs. However, there has yet to be a preventative method that has proven effective.
  • In the short term, cyclosporin as an immunosuppressive agent has been shown to reduce beta cell degeneration.

Clinical presentation

  • These people will usually have a normal BMI
  • Patients will present when beta-cell destruction is such that the remaining beta-cells can no longer secrete enough insulin. High glucose levels may actually induce beta-cell death, thus speeding up the progression of the disease in later stages.
  • Weight loss is a major symptom, and this will fail to correct itself when diet is altered. There will also be ketourea, hyperglycemia, and the presence of autoimmune products. Note that these are only present in 90% of newly presenting patients.
  • The majority of patients present with the classicla presentation of¬†hyperglycaemia, without ketoacidosis. They have symptoms such as polyuria, polydipsia and weight loss. The mean duration of symptoms before presentation is about 10 days.
  • Diabetic Ketoacidosis (DKA)‚Äď is an acute life-threatening medical presentation, less common but more serious than the classical presentation.. It is a result¬†of lack of insulin. In normal function, the liver produces keto acids from deamination of amino acids (this is how the liver gets most of its energy). Keto acids are also produced through metabolism of fatty acids. In diabetes, there is a massive perceived lack of glucose by the body¬†(because little or no¬†glucose can be taken up by cells), and so the body resorts to metabolism of fatty acids, and thus production of ketone bodies as its main source of energy. The body produces two ketoacids in this process, one of which is called acetoacetic acid.¬†This spontaneously breaks down to form acetone which is the smell (of nail polish / varnish) that can be smelt on a person‚Äôs breath who is suffering from type one diabetes
  • Ketoacidosis can also occur in alcoholism. Alcohol blocks the first step in gluconeogenesis, and thus the body has to break down fatty acids to get its energy.
  • Ketoacidosis is also significant because it causes a generalised acidosis.
  • It principally occurs in those with type 1 diabetes, because most people with type two can still utilise enough glucose to prevent this from occurring.
  • It is a medical emergency and a major cause of morbidity. Many type 1 patients present in this state, but it can also occur in those that have been diagnosed and are undergoing treatment.
  • In established diabetes there will usually be a precipitating event for DKA¬†(although one isn‚Äôt always found). This is commonly illness, most usually infection. It occurs because during this episode, patients will lose their appetite, and thus reduce their levels of insulin in a mistaken belief that they no longer need it.
  • During illness, patients need up to 25% extra insulin to help them fight the infection ‚Äď the immune system‚Äôs effectiveness is reduced as a result of diabetes!
  • The mortality rate from ketoacidosis is 5-10% in developed countries. This increases with age.
  • It is estimated that 25% of cases of this could be prevented through better communication to the patient- they should be instructed never to stop taking their insulin!
  • The three key features of DKA are:
    • Hyperglycaemia ‚Äď this has a profound effect on osmosis, and causes osmotic diuresis, leading to dehydration and electrolyte loss. ¬†However, the level of hyperglycaemia is not necessarily related to the level of ketoacidosis. In some cases, only a small hyperglycaemia can cause ketoacidosis, whilst in other patients, there may be massive hyperglycaemia but little or no ketoacidosis.
    • Hyperketonaemia ‚Äď this occurs as a result of very little circulating insulin. The effect is exaggerated by stress proteins, such as those present during illness. This results in the utilization (by the liver via ketogenesis) of loads of free fatty acids for metabolism. The mitochondira of cells will then utilise these for metabolism, producing excess ketones as a result. This results in metabolic acidosis.
    • Metabolic acidosis- When the number of free ketones in the blood exceeds those that can be metabolised, ketoacidosis occurs. This will then force H+ into cells, where it will replace potassium. The potassium will go into the blood, where it may induce vomiting. Otherwise, the potassium ions are lost in the urine. (Thus two possible signs and symptoms of ketoacidosis are high potassium levels in the urine, and vomiting (also containing large amounts of potassium).
    • Only a slight elevation in insulin level is enough to prevent ketogenesis in the liver, and thus reverse or prevent this state.
    • The real danger in this condition is reduced perfusion of the kidneys as a result of fluid and electrolyte depletion. This will result in an inability to excrete the excess hydrogen and ketones, and the patient will die. This process is due to a COMBINATION¬†of high levels of both glucose and ketones. The ketones cause the damage, but the glucose is responsible for much of the fluid and electrolyte depletion.
    • Respiratory compensation for the acidosis will occur, leading to hyperventilation (Kussmaul respiration).
There may also be abdominal pain, which can make diagnosis difficult.
Many patients present coherently, but confusion and stupor are not uncommon. 5% will present in a coma. The most obvious sign is usually dehydration and the eyeball may be lax to pressure.
Body temperature is also often lowered, despite the presence of infection in many cases.
Loss of fluid and electrolytes in a moderate attack is summarised below:
  • Water ‚Äď 6L
  • Sodium ‚Äď 500mmol
  • Chloride ‚Äď 400mmol
  • Potassium ‚Äď 350mmol

Clinical features

  • Polyuria, thirst
  • Weight loss
  • Weakness
  • Nausea / vomiting
  • Leg cramps
  • Blurred vision
  • Abdominal pain
  • Kussmaul breathing
  • Dehydration
  • Hypotension
  • Cold extremities / peripheral cyanosis
  • Tachycardia
  • Hypothermia
  • Smell of acetone
  • Confusion / drowsiness / coma
Some other signs may be confusing. There is often abdominal pain, particularly in children. There may also be raised amylase, but this does not indicate pancreatitis. Leukocytosis also occurs, but this is a stress response, and not necessarily caused by infection (although if infection is present, it will cause this as well).

Management of DKA

Based on Joint British Diabetes Societies Inpatient Care Group guidelines, September 2013 

DKA is a serious and potentially life-threatening presentation. It is a combination of acidosis, hyperglycaemia, and ketonuria. It may be the first presentation of type I diabetes in a child or young adult, but is also a common presentation in type I diabetics with poor insulin compliance. Treatment should be initiated promptly, and needs regular monitoring with (hourly) blood ketone (and glucose) levels, or, if not available, bicarbonate levels on venous blood gas.

You should involve a specialist as soon as possible (ideally within 24 hours), as this has been shown to reduce morbidity and mortality.

Severe DKA is characterised by:

  • Blood ketones >6 mmol/L
  • Bicarb <5 mmol/L
  • pH <7.0
  • Hypokalaemia (k+ <3.5)
  • GCS <12
  • O2 <92% on room air
  • Systolic BP <90
  • HR >100 or <60
  • Raised anion gap

If any of these features are present, the patient should be considered for HDU admission


  • Insulin dose should be based on¬†weight.¬†Sliding scales should not be used, as they can be inaccurate in overweight and pregnant patients
  • The type of insulin regimen is often referred to as a¬†Fixed rate Intravenous Insulin Infusion,¬†or¬†FRIII
  • Check the effectivesness of the FRIII¬†using blood ketones and revise the dose if it is not effective
  • If bedside blood ketone testing is not available, venous blood gasses can be used to asses bicarbonate level, but only for the first 6 hours, as this becomes inaccurate after infusion of large amount of normal saline.
  • Use IV 0.9% sodium chloride (normal saline)
  • If hypotensive (systolic BP <90mmHg) give a bolus of 500mls normal saline. If still hypotensive, seek senior help. Consider discussion with ICU, and think about other possible causes of hypotension.
  • Once hypotension is resolved, or if it is not present at presentation, patient will still require large amounts of IV fluid. A typical regimen might be 1L normal saline in the first hour, then 1L over 2 hours, then 1L over 4 hours etc, but be wary of a ‘one size fits all’ regimen
  • Monitor electrolytes, particularly¬†potassium¬† closely. You will likely need to replace potassium, which can be done by adding KCl to the bags of normal saline. Be careful not to infuse potassium too quickly.

DKA patients are at risk of both hypokalaemia, and hyperkalaemia. Initially they are often hyperkalaemic, but their total body potassium is low. This is because potassium is taken up into cells with insulin, so with a lack of insulin, extra cellular potassium rises, and the intracellular level falls.
Titrate potassium replacement to the potassium level, as measured on hourly venous blood gasses.

  • K+ >5.5mmol/L –¬†dont¬†replace
  • K+ 3.5 – 5.5 mmol/L –¬†replace by using 40mmol/L in infused solution
  • K+ <3.5 –¬†seek senior help – additional potassium replacement may be require

DKA patients are often very sick. As with any sick patient, it is useful to have a systematic approach. Do the basics first:

  • A – Airway
    • ‚ÄčAre they maintaining their own airway?
    • Do you need urgent airway assistance? Consider ICU / anaesthetic input
  • B – Breathing
    • ‚ÄčWhat are the O2 saturations?
    • What is the respiratory rate?
    • Do¬†they need oxygen?
  • C – Circulation
    • ‚ÄčGet IV access
    • Send regular bloods (FBC, U+Es, CRP, formal glucose level, blood cultures)
    • Blood ketone and glucose (bedside testing)
    • Venous blood gas
  • D – Disability¬†(/conscious level)
    • Assess GCS – helps to assess severity of DKA
    • Consider causes for DKA (e.g. infection – send off cultures, check temperature)
  • Start IV fluids –¬†as described above
  • Replace Potassium –¬†as described above
  • Start Fixed Rate Intravenous Insulin Infusion –¬†as described above


  • Re-assess hourly, including bedside ketones and glucose, venous blood gas (VBG) and clinical assessment and examination.
  • The aim is to reduce the ketone level, and stop ketogenesis.
  • Aim for reduction of ketone level of >0.5mmol/L/hr
    • If unable to measure blood ketones, use VBG instead, and aim for bicarbonate rise of >3.0mmol/L/hr, and blood glucose fall of 3.0mmol/L/hr
  • Maintain serum potassium of 3.5 – 5 mmol/L (see above for potassium management)
  • Avoid hypoglycaemia. It may be necessary to use 10% dextrose IV
  • Consider urinary catheter if anuric
  • Consider NG tube if persistent vomiting or obtunded

Resolution of DKA

  • Defined as blood ketones <0.6 mmol/L and venous pH >7.3
  • After 6 hours, bicarbonate level should not be used as a measure of progress, as hyperchloraemia may exist secondary to saline infusion. Hyperchloaraemic acidosis can lower bicarb.
  • Continue to treat precipitating factors
  • If patient is eating and drinking, start subcutaneous insulin. If not, can start a sliding sclae (VRIII – variable rate intravenous insulin infusion)
  • Most cases resolve within 24 hours. If not resolving, seek specialist / senior support urgently.

Long Term Management

Patients will require life-long insulin therapy


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Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) FRACGP currently works as a GP and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University, and is studying for a Masters of Sports Medicine at the University of Queensland. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

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