Professor Merlin Thomas Professor and program leader , Department of Diabetes , Monash University , Melbourne , Victoria .

First published online on 29 September 2023

INTRODUCTION

KETOACIDOSIS is a severe and

life-threatening emergency triggered by a sudden , unimpeded elevation of blood ketone concentrations leading to metabolic acidosis . Ketoacidosis is most commonly observed associated with severe hyperglycaemia in new-onset or inadequately treated type 1 diabetes . 1-3 However , so-called diabetic ketoacidosis ( DKA ) is not the only cause of ketoacidosis . Euglycaemic ketoacidosis may also be triggered in pregnancy with or without diabetes , 4 following severe restriction of dietary carbohydrate intake or starvation , alcohol or cocaine abuse , severe catabolic illness ( for example , sepsis , pancreatitis ), severe liver disease , and in some patients with diabetes treated with sodium-glucose co-transporter 2 ( SGLT2 ) inhibitors . 5

Adding to its seriousness , ketoacidosis is frequently misdiagnosed in general practice , presenting as it does with non-specific symptoms , including nausea , vomiting , abdominal pain , malaise , shortness of breath and confusion . 6 However , when suspected and correctly diagnosed through blood ketone testing , vital emergency care can be rapidly initiated .

This How to Treat covers the identification and initial management of acute ketoacidosis in adults , and aims to ensure GPs can identify adults with ketoacidosis and initiate an emergency referral that can be lifesaving . This article does not address the diagnosis and specialist management of DKA in children and young people , which is a distinct paediatric emergency .

EPIDEMIOLOGY

DIABETIC ketoacidosis ( DKA ) is one of the most important emergencies in type 1 diabetes . 7 Despite improvements in diabetes care and new technologies for insulin delivery and glucose monitoring , at least three in every hundred adults with type 1 diabetes globally may be hospitalised annually due to DKA . 8-10

Data from the Freemantle study suggest DKA may be a little lower in Australian adults with type 1 diabetes ( 1.7 per 100 person-years ) possibly reflecting better resources available to Australian patients . 11

Most DKA events are observed in and around the time of the diagnosis of type 1 diabetes , before insulin therapy starts , or during the first few years of insulin management when

errors in titration , accidental omission , pump failure or poor adherence may sometimes result in inadequate insulin delivery , especially in children and adolescents . At least a third to a half of Australian children with type 1 diabetes initially present with DKA . 12 The risk of DKA is lower in older adults with well-established type 1 diabetes . 8 However , DKA remains a potential threat in type 1 diabetes , even in individuals with no prior history of DKA and good glycaemic control .

For example , in our recent survey of Finnish adults with established type 1 diabetes ( of at least two years ), at least one in six were hospitalised or died from DKA over a 14-year period . Most of these were one-off events ( see figure 1 ). 2 Most of these patients had only one event . 2

Approximately one-third of all patients with type 1 diabetes who present with DKA go on to experience multiple recurrent episodes . 2 In part , this is due to a failure to modify risk factors , including poor adherence , risk-taking behaviour , limited resourcing , diet and lifestyle irregularities .

Importantly , recurrent episodes of DKA are associated with poor clinical outcomes and an increased risk

of premature mortality , although it is not firmly established that episodes of DKA are the cause .

Type 2 diabetes is not generally associated with DKA because of residual insulin production that serves to limit excessive ketogenesis . However , some people with untreated type 2 diabetes may initially present with DKA , particularly African American and Hispanic individuals . 13 This is also known as “ Flatbush diabetes ”. 14 These people do not have type 1 diabetes or autoimmune markers of betacell destruction . However , they are still ‘ ketosis-prone ’, and the profound volume shifts associated with severe hyperglycaemia combined with severe insulin deficiency can , rarely , trigger DKA in susceptible individuals with type 2 diabetes .

After initial treatment , and restoration of beta-cell function with amelioration of glucotoxicity , the rate of DKA in individuals with type 2 diabetes is very low ( about 0.2 events per 1000 patient-years ). 11

Between 5 % and 10 % of all patients presenting with ketoacidosis have plasma glucose levels in the normal range ( less than 11.1mmol / L ). 5 This is known as euglycaemic ketoacidosis