Diabetic ketoacidosis (DKA) is an acute, life‑threatening metabolic complication predominantly associated with diabetes mellitus, most commonly type 1 diabetes, though it can also occur in individuals with type 2 diabetes under conditions of severe insulin deficiency or increased insulin resistance. The condition is characterized by hyperglycemia, metabolic acidosis due to accumulation of ketone bodies, and dehydration.
Pathophysiology
DKA results from an absolute or relative deficiency of insulin coupled with an excess of counter‑regulatory hormones such as glucagon, catecholamines, cortisol, and growth hormone. The insulin deficit impairs glucose utilization by peripheral tissues, leading to pronounced hyperglycemia. Simultaneously, unchecked lipolysis releases free fatty acids that are transported to the liver, where they undergo β‑oxidation and are converted to ketone bodies (acetoacetate, β‑hydroxybutyrate, and acetone). Accumulation of these acids lowers plasma bicarbonate concentration, resulting in a high anion‑gap metabolic acidosis. Osmotic diuresis due to glucosuria contributes to significant fluid and electrolyte losses.
Clinical Presentation
Typical signs and symptoms include:
- Polyuria and polydipsia
- Nausea, vomiting, and abdominal pain
- Dehydration (dry mucous membranes, tachycardia, hypotension)
- Altered mental status ranging from lethargy to coma
- Fruity‑smelling breath (acetone)
- Kussmaul respirations (deep, rapid breathing) as a compensatory respiratory response to acidosis
Diagnostic Criteria
Diagnosis is based on laboratory findings that commonly meet the following thresholds:
| Parameter | Typical Threshold |
|---|---|
| Plasma glucose | >250 mg/dL (13.9 mmol/L) |
| Arterial pH | <7.3 |
| Serum bicarbonate | <18 mmol/L |
| Anion gap | >10‑12 mmol/L |
| Serum ketones | Positive (β‑hydroxybutyrate >3 mmol/L or urine ketones) |
Additional investigations may assess serum electrolytes (particularly potassium), renal function, and potential precipitating factors such as infection, myocardial infarction, or medication non‑adherence.
Management
Prompt treatment in an acute care setting is essential and follows three principal goals:
- Fluid Resuscitation – Isotonic saline (0.9% NaCl) is administered to restore intravascular volume, typically beginning with 15‑20 mL/kg over the first hour, followed by adjustments based on hemodynamic response and serum sodium.
- Insulin Therapy – Continuous intravenous regular insulin infusion (0.1 U/kg/h) is initiated after an initial bolus may be given. Insulin lowers plasma glucose, suppresses ketogenesis, and facilitates intracellular potassium uptake.
- Electrolyte Replacement – Potassium replacement is critical, as insulin-driven intracellular shift can precipitate hypokalemia. Guidelines recommend initiating potassium supplementation when serum potassium is ≤5.0 mmol/L and withholding insulin if potassium is <3.3 mmol/L until corrected.
Adjunctive measures include correction of acidosis (generally achieved through insulin and volume resuscitation without routine bicarbonate administration unless pH < 6.9), monitoring for cerebral edema (particularly in pediatric patients), and treatment of underlying precipitating causes.
Epidemiology
DKA accounts for approximately 4‑8% of all diabetes‑related hospital admissions in the United States and is a leading cause of mortality among individuals with type 1 diabetes, especially in younger patients. Incidence varies globally, with higher rates observed in regions where diabetes care access is limited.
Prognosis
With timely, guideline‑directed therapy, mortality rates have declined to less than 5% in developed settings. Delayed treatment, severe dehydration, profound electrolyte disturbances, or concomitant infection increase the risk of complications such as cerebral edema, acute respiratory distress syndrome, and renal failure.
Prevention
Preventive strategies focus on patient education concerning sick‑day management, adherence to insulin regimens, and early recognition of hyperglycemia. Routine monitoring of blood glucose and ketone levels during illness, stress, or insulin omission can avert progression to DKA.
References
- American Diabetes Association. “Diabetes Care in the Hospital: A Consensus Report.” Diabetes Care, 2023.
- Kitabchi AE, et al. “Hyperglycemic Crises in Adult Patients with Diabetes.” Diabetes Care, 2022.
- International Society for Pediatric and Adolescent Diabetes (ISPAD). “Guidelines for the Management of Diabetic Ketoacidosis.” 2021.