Diabetic Ketoacidosis: Symptoms, Causes, and Treatment

Diabetic ketoacidosis (DKA) is the most frequent hyperglycemic emergency and a leading cause of death in people with diabetes, especially those with type 1 diabetes1 . It occurs when the body lacks sufficient insulin, leading to high blood sugar and the buildup of acids called ketones in the blood2 . Prompt recognition and treatment of DKA are critical to reduce morbidity and mortality1 . This article provides a comprehensive overview of the types, symptoms, causes, diagnosis, treatment, prevention, comorbidities, and management of diabetic ketoacidosis.

Types of Diabetic Ketoacidosis

Diabetic ketoacidosis can present in two main forms: hyperglycemic DKA and euglycemic DKA. Understanding these types is essential for accurate diagnosis and treatment.

Hyperglycemic DKA

Hyperglycemic DKA is the classic form characterized by markedly elevated blood glucose levels, often exceeding 250 mg/dL3 . When blood glucose surpasses the renal threshold of approximately 180 mg/dL, glucose spills into the urine, causing osmotic diuresis4 . This leads to dehydration and loss of electrolytes, which are hallmark features of DKA symptomatology5 . The resulting hyperglycemia, dehydration, and metabolic acidosis define this typical presentation6 .

Euglycemic DKA

Euglycemic diabetic ketoacidosis is a less common but important variant where ketoacidosis occurs despite normal or mildly elevated blood glucose levels, typically below 200 mg/dL7 6. This form can be a diagnostic challenge due to the absence of significant hyperglycemia8 . Euglycemic DKA is often associated with the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors such as canagliflozin, dapagliflozin, and empagliflozin9 . These medications increase the risk by promoting glucagon secretion and decreasing urinary ketone excretion, leading to ketosis without marked hyperglycemia10 . Patients on SGLT2 inhibitors are advised to monitor ketone levels regularly to detect early signs of ketoacidosis11 .

Diabetic Ketoacidosis Symptoms

Symptoms of DKA can range from mild to severe and vary among individuals12 . Early signs often include symptoms related to hyperglycemia such as excessive thirst and frequent urination12 13. As the condition progresses, more severe symptoms may develop, including:

Abdominal pain and vomiting12 13
Rapid, deep breathing known as Kussmaul respirations, a compensatory response to metabolic acidosis5 14
Fruity-smelling breath due to acetone accumulation12 2
Dry skin and mouth, flushed face13
Muscle stiffness or aches13
Fatigue and weakness12 13
Altered mental status, confusion, or decreased alertness in severe cases12 1314

DKA symptoms can develop rapidly, often within 24 hours, and may be the first sign of diabetes in some individuals2 15.

Diabetic Ketoacidosis Causes

DKA results from an absolute or relative deficiency of insulin combined with increased levels of counter-regulatory hormones such as glucagon, cortisol, and catecholamines5 1. This hormonal imbalance leads to increased gluconeogenesis, glycogenolysis, and lipolysis, causing hyperglycemia and ketone production1 16.

Common precipitating factors include:

Non-adherence to insulin therapy, the leading cause especially in type 1 diabetes17 18
Infections such as pneumonia and urinary tract infections, which increase insulin demand19 20
Technical issues with insulin delivery systems, including pump malfunctions21
Use of SGLT2 inhibitors, which predispose to euglycemic DKA10 9
Physiological stressors such as pregnancy and fasting22
Other triggers include physical or emotional trauma, surgery, alcohol or drug misuse (notably cocaine), and certain medications like corticosteroids and diuretics23 2015

Diagnosing Diabetic Ketoacidosis

Diagnosis of DKA integrates clinical presentation with laboratory findings1 . The key diagnostic criteria include:

Blood glucose typically greater than 250 mg/dL, though lower levels may be seen in euglycemic DKA1 6
Presence of ketosis confirmed by ketones in blood or urine1 4
Metabolic acidosis characterized by arterial pH less than 7.30 and serum bicarbonate below 18 mmol/L1 24

Additional clinical signs supporting diagnosis are:

Fruity odor on the breath12 2
Kussmaul breathing as a compensatory mechanism for acidosis5
Altered mental status in severe cases12 14
Leukocytosis, often due to infection or stress12

Laboratory evaluation also includes calculation of the anion gap, which is elevated in DKA due to accumulation of ketoacids1 . Early diagnosis and management are crucial to reduce complications and mortality1 .

Diabetic Ketoacidosis Treatment

Treatment of DKA focuses on correcting hyperglycemia, dehydration, and electrolyte imbalances while addressing precipitating factors1 17. Key components include:

Fluid resuscitation: Intravenous fluids are essential to restore circulatory volume and correct dehydration caused by osmotic diuresis1 3
Insulin therapy: Continuous intravenous insulin infusion is the standard to reduce blood glucose and suppress ketogenesis1 25
Electrolyte replacement: Potassium supplementation is often necessary due to intracellular shifts caused by insulin therapy and losses from diuresis26 27
Monitoring: Frequent blood glucose and electrolyte monitoring guide therapy adjustments and prevent complications such as hypoglycemia and hypokalemia1 26
Addressing precipitating factors: Prompt treatment of infections or other triggers is vital for recovery20

Gradual reduction of blood glucose is recommended to avoid cerebral edema, especially in children28 29. Fluid therapy remains the cornerstone of treatment to restore volume and improve renal perfusion1 .

Preventing Diabetic Ketoacidosis

Prevention strategies focus on patient education, adherence to insulin therapy, and early recognition of precipitating factors30 2. Key preventive measures include:

Regular blood glucose monitoring and ketone testing during illness or high glucose levels31 13
Consistent insulin administration and dose adjustments based on lifestyle and health status30 13
Patient education on sick-day management and when to seek medical care30 15
Monitoring for technical issues in insulin delivery devices21
Early treatment of infections and other stressors20

Hospitalization is required for DKA management due to the need for close monitoring and treatment3 . Preventing DKA reduces hospital admissions and improves patient outcomes30 .

Diabetic Ketoacidosis Comorbidities

DKA is a serious and potentially fatal complication of diabetes32 . Comorbid conditions can complicate its management and worsen prognosis. Notably:

Chronic kidney disease impairs fluid clearance, complicating fluid management in DKA33
Renal impairment requires tailored treatment approaches to avoid fluid overload and electrolyte imbalances33
Other comorbidities such as cardiovascular disease and infections increase mortality risk17 29

Disclosure of comorbid conditions is important for individualized DKA treatment planning33 .

Managing Diabetic Ketoacidosis

“Diabetic ketoacidosis is a life-threatening complication of diabetes, and any delay in treatment can lead to death. The disorder can present with varied signs and symptoms and affects many organs; thus, it is best managed by an interprofessional team dedicated to the management of patients with diabetes mellitus.”
— Jenna M. Lizzo, Amandeep Goyal, Vikas Gupta34

Effective management of DKA requires a multidisciplinary approach involving emergency, endocrinology, infectious disease, and critical care teams34 . Key aspects include:

Rapid assessment and stabilization of airway, breathing, and circulation29
Frequent monitoring of vital signs, glucose, electrolytes, and acid-base status1 29
Use of standardized treatment protocols to ensure consistent care and reduce complications35
Transitioning to subcutaneous insulin once DKA resolves, with patient education on insulin regimen and prevention1 29
Addressing psychosocial factors such as substance abuse and medication adherence to prevent recurrence17 18