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Handbook of Diabetes, 4th Edition, Excerpt #11: Diabetic Ketoacidosis, Hyperglycaemic Hyperosmolar State and Lactic Acidosis

Sep 27, 2014

Rudy Bilous, MD, FRCP
Richard Donnelly, MD, PHD, FRCP, FRACP

handbook-of-diabetes-imageDiabetic ketoacidosis (DKA) is a state of severe uncontrolled diabetes caused by insulin deficiency. It is characterised by hyperglycaemia, hyperketonaemia and metabolic acidosis, and has been somewhat arbitrarily divided into mild, moderate and severe based upon biochemical and clinical features (Table 12.1)….



The frequency of DKA increased by 35% in the USA in the decade 1996 – 2006, with an estimated 135,000 hospital admissions per year costing around 2.4 billion US dollars. Incidence rates of 1 – 5% have been reported worldwide and are higher in younger type 1 patients and females. In the UK there were 12,326 emergency admissions coded as DKA in the 12 months to March 2007. Admission rates for children < 15 years of age in the UK range between 0.05 and 0.38 per patient-year. Overall mortality in developed countries is reportedly low (<1 – 5%) but much higher in older patients, probably as a result of the underlying cause (often cardiovascular disease). However, DKA accounts for more than 50% of all deaths in people with type 1 diabetes < 24 years of age in the USA (Figure 12.1 ).


Although DKA mainly occurs in type 1 patients, it can occur in African American and Hispanic people who subsequently can be managed without insulin and thus behave as type 2 diabetes. This phenomenon is now termed ‘ketosis-prone type 2 diabetes’; it can account for 25 – 50% of African American or Hispanic cases of DKA. Their clinical characteristics are shown in Box 12.1.

Box 12.1 Features of ketosis-prone type 2 diabetes mellitus

Acute presentation
• Mean age > 40
• Male preponderance
• BMI ≥ 28 (for African American, less for Hispanic and Taiwanese)
• Mostly newly diagnosed with diabetes
• Strong family history of type 2 diabetes
• HbA1c at presentation > 12%
• Autoimmune markers for type 1 diabetes negative
• Fasting C – peptide detectable
• Most do not require long-term insulin therapy


Precipitating factors for diabetic ketoacidosis

The most common precipitating factor is intercurrent infection (19 – 56%) but it is important to remember that a polymorphonucleocytosis is common in DKA, probably secondary to physiological stress, and does not necessarily imply sepsis. Other causes of DKA and their range of frequency from reported series are shown in Table 12.2. The frequency of cause will vary according to age and ethnicity. Not infrequently, no obvious cause is found.

Recurrent DKA is a feature particularly in young girls and can account for up to 15% of all admissions in some series.


Relative or absolute insulin deficiency in the presence of catabolic counter-regulatory stress hormones (particularly glucagon and catecholamines, but also growth hormone and cortisol) leads to hepatic overproduction of glucose and ketones. Lack of insulin combined with excess stress hormones promotes lipolysis, with the release of NEFAs from adipose tissue into the circulation. In the liver, fatty acids are partially oxidised to the ketone bodies acetoacetic acid and 3-hydroxybutyric acid, which contribute to the acidosis, and acetone (formed by the non-enzymatic decarboxylation of acetoacetate). The latter is volatile and excreted via the lungs.

Hyperglycaemia results from increased glycogenolysis secondary to glucagon excess; gluoconeogenesis as a result of increased lipolysis and proteolysis; diminished peripheral uptake of glucose due to absent insulin stimulated uptake; and utilisation of alternative fuels such as NEFA and ketone bodies in preference to glucose.