Diabetic Ketoacidosis ¹

Abstract

Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present -'D', either elevated blood glucose levels or a family history of diabetes mellitus; 'K', the presence of high urinary or blood ketoacids; and 'A', a high anion gap metabolic acidosis. Early diagnosis and management is paramount to improve patient outcome. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with an appreciable, although largely preventable morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA, as well as we provide practical recommendations for management of DKA in adults and children. [H1] IntroductionDiabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. DKA is the consequence of an absolute (that is, total absence of) or relative (that is, levels insufficient to supress ketone production) lack of insulin and concomitant elevation of counter-regulatory hormones, usually resulting in the triad of hyperglycaemia, metabolic acidosis and ketosis (elevated levels of ketones in the blood or urine; serum ketone concentration of >3.0mmol/l), often accompanied by varying degrees of circulatory volume depletion [G]. DKA occurs mostly in people with uncontrolled type 1 diabetes mellitus (T1DM, which results from the autoimmune destruction of the β-cells of the islets of Langerhans), but can also occur in adults with poorly controlled type 2 diabetes mellitus (T2DM, a result of impaired insulin secretion or action) under stressful conditions such as acute medical or surgical illnesses and, in adolescents, new onset T2DM (also known as ketosis-prone T2DM) (Figure 1). Although any illness or physiological stress can precipitate DKA, the most frequent causes are infections, particularly urinary tract infections and gastroenteritis 1,2 . DKA was previously considered to be a key clinical feature of T1DM, but has been documented in children and adults with newly diagnosed T2DM 2,3 . Although ketosis-prone T2DM can occur in all populations, epidemiological data suggest that people of African or Hispanic origin seem to be at greater risk 2 . This predisposition likely has a genetic component, but this has yet to be elucidated. Most often individuals with ketosis-prone T2DM have obesity and a strong family history of T2DM and evidence of insulin resistance. Despite presenting with DKA and decreased insulin concentrations, on immunological testing these individuals have the same frequency of the typical autoimmune markers of T1DM such as islet cell, insulin, glutamic acid decarboxylase, and protein tyrosine phosphatase autoantibodies as those who present with HHS and their β-cell function recovers with restoration of insulin secretion quickly after trea...