Diabetic Ketoacidosis (DKA)

A 24-year-old woman with known type 1 diabetes mellitus presents with a 2-day history of polyuria, polydipsia, nausea, and vomiting. She also reports abdominal pain and increasing fatigue. She recently had a febrile illness and missed several doses of insulin. On examination, she is dehydrated, tachycardic, and hypotensive. Her breathing is deep and rapid, and a fruity odor is noted on her breath. She is drowsy but arousable. Laboratory investigations show blood glucose 380 mg/dL, arterial pH 7.15, serum bicarbonate 12 mmol/L, and elevated serum ketones (β-hydroxybutyrate). Serum potassium is 5.2 mmol/L with a high anion gap metabolic acidosis. Diagnosis?

Diagnosis is Diabetic Ketoacidosis (DKA), moderate severity by acid-base criteria.

The combination of hyperglycemia, ketonemia, metabolic acidosis, dehydration, Kussmaul respiration, and missed insulin doses is diagnostic of DKA.

1. Definition

1.      Diabetic ketoacidosis is an acute, potentially life-threatening hyperglycemic emergency caused by severe insulin deficiency.

2.      Diagnosis requires all three components:

1.      Diabetes or hyperglycemia

1.      Plasma glucose ≥200 mg/dL

2.      Or a prior history of diabetes regardless of presenting glucose

2.      Ketosis

1.      β-hydroxybutyrate ≥3.0 mmol/L

2.      Or urine ketones ≥2+ if blood ketone measurement is unavailable

3.      Metabolic acidosis

1.      pH <7.3

2.      And/or serum bicarbonate <18 mmol/L

3.      DKA can occur with glucose <200 mg/dL, termed euglycemic DKA.

2. Etiology / Precipitating Factors

1.      DKA results from absolute or relative insulin deficiency combined with increased counter-regulatory hormones.

2.      Common precipitants include:

1.      Insulin omission or inadequate insulin administration

2.      Infection

3.      New-onset diabetes

4.      Myocardial infarction

5.      Stroke

6.      Pancreatitis

7.      Surgery or trauma

8.      Pregnancy

9.      Glucocorticoids and other medications that worsen hyperglycemia

3.      SGLT2 inhibitors are an important cause of euglycemic DKA.

4.      Other causes of euglycemic DKA include:

1.      Pregnancy

2.      Reduced caloric intake or starvation

3.      Alcohol use

4.      Liver failure or impaired gluconeogenesis

5.      Partial insulin treatment

In this patient, the most likely precipitants are recent febrile illness and insulin omission.

3. Pathophysiology

1.      Insulin deficiency reduces peripheral glucose utilization.

2.      Increased glucagon, catecholamines, cortisol, and growth hormone promote:

1.      Gluconeogenesis

2.      Glycogenolysis

3.      Hyperglycemia

3.      Hyperglycemia produces osmotic diuresis, causing:

1.      Water loss

2.      Sodium loss

3.      Potassium loss

4.      Dehydration

5.      Reduced renal perfusion

4.      Insulin deficiency also stimulates lipolysis.

5.      Free fatty acids are converted in the liver to ketone bodies:

1.      β-hydroxybutyrate

2.      Acetoacetate

3.      Acetone

6.      β-hydroxybutyrate is the predominant ketoacid in DKA.

7.      Accumulation of ketoacids produces high anion gap metabolic acidosis.

8.      Acetone contributes to the characteristic fruity breath odor.

4. Clinical Features

4.1 Hyperglycemic Symptoms

1.      Polyuria

2.      Polydipsia

3.      Weight loss

4.      Fatigue

4.2 Gastrointestinal Features

1.      Nausea

2.      Vomiting

3.      Abdominal pain

Abdominal pain can be prominent in severe acidosis and may improve as DKA resolves.

4.3 Respiratory Features

1.      Kussmaul respiration

1.      Deep, rapid breathing caused by respiratory compensation for metabolic acidosis

2.      Fruity or acetone breath

4.4 Volume Depletion

1.      Dry mucous membranes

2.      Tachycardia

3.      Hypotension

4.      Reduced skin turgor

5.      Oliguria in severe dehydration

4.5 Neurological Features

1.      Alertness may be preserved in mild disease.

2.      More severe disease may cause:

1.      Drowsiness

2.      Confusion

3.      Stupor

4.      Coma

5. Diagnosis

5.1 Diagnostic Criteria

All three are required:

1.      Diabetes / hyperglycemia

1.      Glucose ≥200 mg/dL

2.      Or known diabetes

2.      Ketosis

1.      β-hydroxybutyrate ≥3.0 mmol/L

2.      Blood β-hydroxybutyrate is preferred over urine ketones

3.      Acidosis

1.      pH <7.3

2.      And/or bicarbonate <18 mmol/L

5.2 Severity Classification

Mild DKA

1.      β-hydroxybutyrate 3.0 to 6.0 mmol/L

2.      pH >7.25 to <7.30 or bicarbonate 15 to 18 mmol/L

3.      Usually alert

Moderate DKA

1.      β-hydroxybutyrate 3.0 to 6.0 mmol/L

2.      pH 7.0 to 7.25

3.      Bicarbonate 10 to <15 mmol/L

4.      Mental status may be alert or drowsy

Severe DKA

1.      β-hydroxybutyrate >6.0 mmol/L

2.      pH <7.0

3.      Bicarbonate <10 mmol/L

4.      Stupor or coma may occur

Not every severity variable must fall into the same category, and level of care should be based on the overall clinical condition.

This patient has pH 7.15, bicarbonate 12 mmol/L, and drowsiness, which are consistent with moderate DKA.

Because she is also hypotensive and drowsy, she is not an uncomplicated moderate DKA patient suitable for routine ward-based or subcutaneous management. She requires IV insulin and higher-acuity monitored care, with step-down or ICU placement determined by hemodynamic response, mental status, and overall clinical condition.

5.3 Additional Laboratory Findings

1.      High anion gap metabolic acidosis

1.      Strongly supportive

2.      Not required when direct ketone and acid-base criteria are available

2.      Serum potassium may initially be normal or elevated despite a substantial total-body potassium deficit.

3.      BUN and creatinine may increase because of volume depletion and reduced renal perfusion.

4.      Serum sodium may be reduced because hyperglycemia causes osmotic movement of water into the extracellular space.

5.      Serum phosphate may fall during treatment.

6. Differential Diagnosis

1.      Hyperosmolar hyperglycemic state

2.      Alcoholic ketoacidosis

3.      Starvation ketoacidosis

4.      Lactic acidosis

5.      Methanol poisoning

6.      Ethylene glycol poisoning

7.      Salicylate toxicity

8.      Uremic acidosis

9.      Mixed DKA-HHS

7. Management

The major treatment components are:

1.      Fluid resuscitation

2.      Potassium-guided insulin therapy

3.      Electrolyte replacement

4.      Treatment of the precipitating cause

5.      Frequent biochemical and clinical monitoring

7.1 Fluid Therapy

1.      In adults without significant cardiac or renal compromise, begin:

1.      Isotonic saline or a balanced crystalloid

2.      Initial rate approximately 500 to 1,000 mL/hour during the first 2 to 4 hours

2.      Balanced crystalloids may reduce hyperchloremic acidosis and may result in faster DKA resolution compared with large-volume normal saline.

3.      Subsequent fluid therapy should be individualized according to:

1.      Blood pressure

2.      Heart rate

3.      Hydration status

4.      Urine output

5.      Serum sodium

6.      Cardiac and renal function

4.      Use more cautious fluid replacement in patients at risk of fluid overload.

5.      When glucose falls below 250 mg/dL:

1.      Add 5% to 10% dextrose

2.      Continue insulin until ketoacidosis resolves

7.2 Potassium Management

Despite the elevated serum potassium often seen initially, DKA produces a major total-body potassium deficit.

If potassium <3.5 mmol/L

1.      Delay insulin therapy

2.      Begin potassium replacement

3.      A typical initial replacement rate is approximately 10 mmol/hour

4.      Start insulin only after potassium rises above 3.5 mmol/L

If potassium 3.5 to <5.0 mmol/L

1.      Start insulin.

2.      Add approximately 20 to 30 mmol potassium per liter of IV fluid.

3.      Target serum potassium is approximately 4 to 5 mmol/L.

If potassium ≥5.0 mmol/L

1.      Do not initially give potassium.

2.      Monitor closely.

3.      Begin potassium replacement when the concentration falls below 5.0 mmol/L.

This patient's potassium is 5.2 mmol/L, so insulin can be started without initial potassium replacement, with close monitoring because potassium will usually fall during treatment.

7.3 Insulin Therapy

1.      Start insulin after confirming serum potassium is >3.5 mmol/L.

2.      Preferred treatment for significant DKA:

1.      IV regular insulin infusion at 0.1 units/kg/hour

3.      Routine IV insulin bolus is not necessary when the infusion can be started promptly.

4.      When glucose falls below 250 mg/dL:

1.      Add 5% to 10% dextrose

2.      Reduce IV insulin to approximately 0.05 units/kg/hour

5.      Adjust therapy to maintain glucose around 200 mg/dL while ketosis and acidosis continue to resolve.

6.      Do not stop insulin simply because glucose has normalized.

7.      Continue insulin until biochemical resolution of ketoacidosis.

7.4 Subcutaneous Insulin for Selected Patients

1.      Subcutaneous rapid-acting insulin given every 1 to 2 hours can be used for selected patients with uncomplicated mild or moderate DKA when adequate monitoring is available.

2.      It is not appropriate for patients with:

1.      Severe DKA

2.      Hemodynamic instability

3.      Significant alteration in mental status

4.      Other critical illness

Because this patient is hypotensive and drowsy, IV insulin with higher-acuity inpatient monitoring is more appropriate.

7.5 Bicarbonate Therapy

1.      Routine bicarbonate therapy is not recommended.

2.      Consider bicarbonate only in severe acidosis with pH <7.0.

3.      Potential complications of unnecessary bicarbonate include:

1.      Hypokalemia

2.      Paradoxical CNS acidosis

3.      Delayed ketone clearance

7.6 Phosphate Therapy

1.      Routine phosphate replacement is not recommended.

2.      Consider replacement when:

1.      Serum phosphate is <1.0 mmol/L

2.      And there is clinically significant muscle weakness, particularly respiratory or cardiac compromise

3.      Excessive phosphate replacement can cause hypocalcemia.

7.7 Treat the Precipitating Cause

1.      Search for and treat the underlying trigger.

2.      Examples include:

1.      Infection

2.      Insulin omission or delivery failure

3.      Myocardial infarction

4.      Stroke

5.      Pancreatitis

3.      Antibiotics should be administered when bacterial infection is suspected or confirmed, not simply because DKA is present.

8. Monitoring

During active treatment:

1.      Capillary blood glucose every 1 to 2 hours

2.      Approximately every 4 hours:

1.      Electrolytes

2.      Creatinine

3.      Phosphate

4.      β-hydroxybutyrate

5.      Venous pH

3.      Potassium should be checked approximately 2 hours after starting insulin and then at least every 4 hours until DKA resolves.

4.      Monitor:

1.      Vital signs

2.      Neurological status

3.      Fluid balance

4.      Urine output

5.      Venous blood gas is generally sufficient for acid-base monitoring.

6.      Arterial blood gas is not routinely necessary unless there is concern about oxygenation or significant respiratory disease.

9. Resolution of DKA

DKA is considered resolved when:

1.      β-hydroxybutyrate <0.6 mmol/L

and

2.      Venous pH ≥7.3 or bicarbonate ≥18 mmol/L

Ideally:

3.      Blood glucose is <200 mg/dL

Important points:

1.      Anion gap should not be used as the primary resolution criterion, because treatment with chloride-rich fluids may cause persistent hyperchloremic non-anion gap acidosis.

2.      Urine ketones should not be used to determine resolution, because β-hydroxybutyrate is converted back to acetoacetate during recovery.

10. Transition to Subcutaneous Insulin

1.      Once DKA has resolved, transition to an appropriate subcutaneous insulin regimen.

2.      A basal-bolus insulin regimen is generally preferred.

3.      Administer subcutaneous basal insulin about 2 hours before discontinuing the IV insulin infusion to provide adequate overlap and reduce the risk of rebound hyperglycemia and recurrent ketosis.

4.      In patients with type 1 diabetes, continuous basal insulin coverage is essential.

5.      Before discharge:

1.      Review the precipitating factor

2.      Ensure access to insulin and supplies

3.      Reinforce sick-day management

4.      Review blood or urine ketone monitoring

5.      Emphasize that basal insulin should not be omitted during illness, even when oral intake is reduced

11. Complications

Complications of DKA or its treatment include:

1.      Hypokalemia

2.      Hypoglycemia

3.      Hyperchloremic non-anion gap metabolic acidosis

4.      Acute kidney injury

5.      Thrombosis

6.      Pulmonary complications

7.      Cerebral edema

1.      Rare in adults

2.      More common in children

Osmotic demyelination is primarily a concern with inappropriate correction of severe hyperosmolality or sodium abnormalities, particularly in HHS, and is not a typical complication of uncomplicated DKA.

12. Key Clinical Insight

Polyuria + polydipsia + vomiting + abdominal pain + dehydration + Kussmaul respiration + ketonemia + metabolic acidosis strongly suggests DKA.

In this patient, recent illness and missed insulin doses are likely precipitants, and the pH of 7.15 with bicarbonate 12 mmol/L is consistent with moderate DKA. Her hypotension and drowsiness indicate the need for higher-acuity monitored care despite the biochemical classification.

References

1.      American Diabetes Association Professional Practice Committee for Diabetes. 16. Diabetes Care in the Hospital: Standards of Care in Diabetes-2026. Diabetes Care. 2026;49(Suppl 1):S339-S355. doi:10.2337/dc26-S016.

2.      Umpierrez GE, Davis GM, ElSayed NA, et al. Hyperglycemic Crises in Adults With Diabetes: A Consensus Report. Diabetes Care. 2024;47(8):1257-1275. doi:10.2337/dci24-0032.

3.      American Diabetes Association Professional Practice Committee for Diabetes. 6. Glycemic Goals, Hypoglycemia, and Hyperglycemic Crises: Standards of Care in Diabetes-2026. Diabetes Care. 2026;49(Suppl 1):S132-S149. doi:10.2337/dc26-S006.