Diabetic Ketoacidosis (DKA)

Diabetic ketoacidosis (DKA) is an acute, life-threatening metabolic emergency characterized by:

• Hyperglycemia
• Ketosis
• High anion gap metabolic acidosis

It results from absolute or relative insulin deficiency combined with increased counter-regulatory hormones:

• Glucagon
• Catecholamines
• Cortisol
• Growth hormone

DKA occurs most commonly in:

• Type 1 Diabetes Mellitus
  but can also occur in:
• Type 2 Diabetes Mellitus
  especially during severe stress or with SGLT2 inhibitor use.

Diagnostic Criteria 

Classical Diagnostic Triad

The arterial pH may be normal or even raised if other types of metabolic or respiratory alkalosis coexist, eg, in individuals with vomiting or diuretic use.

In Diabetic Ketoacidosis, metabolic acidosis is always present by definition, because ketone bodies (β-hydroxybutyrate, acetoacetate) accumulate.

But the arterial pH may sometimes appear near normal because of strong respiratory compensation from hyperventilation (Kussmaul breathing).

The primary disorder is:

• ↓ HCO₃⁻ → metabolic acidosis

Compensation:

• Hyperventilation → ↓ PaCO₂ → raises pH toward normal

So you can see situations like:

This is still DKA despite “normal” pH.

Important points:

• Low bicarbonate + high anion gap + ketones are more reliable than pH alone.
• Venous/arterial pH can be:
• low → usual DKA
• near normal → compensated DKA
• occasionally alkalemic if mixed disorder exists (e.g., vomiting causing metabolic alkalosis)

Winter’s formula helps determine if respiratory compensation is appropriate:

PaCO_2 = (1.5 \times HCO_3^-) + 8 \pm 2

If measured PaCO₂ is:

• higher than expected → superimposed respiratory acidosis
• lower than expected → additional respiratory alkalosis

So, normal pH does not exclude DKA.

Severity Classification 

Pathophysiology 

Absolute or Relative Insulin Deficiency

Causes:

• Reduced glucose utilization
• Increased hepatic glucose production
• Increased lipolysis
• Ketogenesis

Hormonal Changes

Metabolic Pathogenesis

1. Hyperglycemia

Mechanisms:

• Increased gluconeogenesis
• Glycogenolysis
• Reduced peripheral uptake

Result:Severe hyperglycemia/Osmotic diuresis

2. Ketogenesis

Insulin deficiency activates:

• Hormone-sensitive lipase

Fat breakdown → free fatty acids → liver.

In liver:

• β-oxidation converts FFAs to ketone bodies:
• Acetoacetate
• β-hydroxybutyrate
• Acetone

Result:Metabolic acidosis

3. Osmotic Diuresis

Hyperglycemia exceeds renal threshold.

Consequences:

• Polyuria
• Sodium loss
• Potassium loss
• Magnesium/phosphate loss(serum phosphate level in DKA may be elevated despite total-body phosphate depletion.)
• Severe dehydration

Typical fluid deficit:5–8 L

Precipitating Factors

Euglycemic DKA

Definition

DKA with:

• Glucose <250 mg/dL
• Significant ketosis and acidosis

Associated with:

• Starvation
• Pregnancy
• Alcohol use
• SGLT2 inhibitors

Common drugs:Empagliflozin/Dapagliflozin/Canagliflozin

Clinical Features

Symptoms

Signs

Kussmaul Respiration

Deep, labored,tachypneic  respiration due to severe metabolic acidosis.

Purpose:

• Reduce PaCO₂
• Compensate acidosis

Laboratory Findings

In Diabetic Ketoacidosis, the main ketone body is β-hydroxybutyrate (3-HB), not acetoacetate.

Normally:β-hydroxybutyrate : acetoacetate ratio ≈ 1:1

But in severe DKA:

• ratio may increase to 10:1
• meaning much more β-hydroxybutyrate is produced.

The commonly used nitroprusside ketone test (urine ketone strip):detects only acetoacetate

• does NOT detect β-hydroxybutyrate properly.

So in early severe DKA:ketone strip may underestimate severity.

During Treatment

When insulin is given:β-hydroxybutyrate decreases first

• it gets converted into acetoacetate

So paradoxically:urine ketone test may become more positive initially,even though the patient is actually improving.

Serum Potassium in DKA

Total body potassium is depleted despite normal/high serum K⁺.

Why?

• Acidosis shifts K⁺ extracellularly
• Insulin deficiency prevents cellular uptake

Once insulin therapy starts:K⁺ rapidly falls

Hence:Frequent monitoring mandatory

Corrected Sodium in DKA

Hyperglycemia lowers measured sodium.

Formula:Corrected Na+=Measured Na+ +1.6×100(Glucose−100)

(Glucose in mg/dL)

Effective Serum Osmolality=2(Na+)+18Glucose

Anion Gap

Anion Gap=Na+−(Cl−+HCO3− )

Normal:8–12 mEq/L

Differential Diagnosis

Management of DKA

ICU Indications

Fluid Therapy in DKA

Initial Fluid:First Hour

• 0.9% saline 15–20 mL/kg
• Usually 1–1.5 L first hour

Subsequent Fluid Choice

Maintenance Fluid rate -250–500 mL/hour 

Because the average DKA patient has:

• 5–8 L total fluid deficit(10% to 15% of the body weight.)

Typical replacement:

• About 50% deficit in first 8–12 hours
• Remaining over next 12–24 hours

When Glucose Falls to 200 mg/dL

Add dextrose:D5 + 0.45% saline

Goal:Continue insulin safely and Clear ketones

Role of Balanced Crystalloids

Balanced crystalloids (e.g., Ringer’s Lactate) may:

• Reduce hyperchloremic acidosis
• Improve renal outcomes

Increasingly guideline-supported.

American Diabetes Association

• Fluid therapy must be individualized in:
• HF
• renal failure
• elderly

Insulin Therapy

Insulin must continue until:Anion gap closes and Ketosis resolves

NOT merely until glucose normalizes.

IV Regular Insulin

Standard Regimen —Continuous Infusion 0.1 U/kg/hour IV

Some protocols:

• Bolus 0.1 U/kg then infusion
• Others omit bolus(hourly insulin infusion at 0.14 U/kg/hr.)

Target Glucose Fall

Desired fall:50–75 mg/dL/hour

If not falling adequately: Increase infusion rate

When Glucose <200 mg/dL

Reduce insulin infusion: 0.02–0.05 U/kg/hr

Continue dextrose infusion.

In a patient with euglycemic DKA (glucose level <250 mg/dL), insulin boluses should not be administered to prevent a rapid decline in blood glucose levels. The insulin infusion is given at a lower rate of 0.05 U/kg/hr. These patients should receive dextrose 5% to 10% in the fluids from the beginning.

Potassium Management in DKA

Bicarbonate Therapy

Not routinely recommended.

Potential harms:

• Paradoxical Cerebral acidosis
• Hypokalemia
• Cerebral edema

When Bicarbonate is Considered

Phosphate Replacement

Usually Not Routine

Consider if:Severe hypophosphatemia(1.0 mg/dl)

Monitoring in DKA

Resolution Criteria of DKA

Transition to Subcutaneous Insulin

Overlap IV insulin with SC insulin by:1–2 hours

Reason:Prevent rebound ketosis

Stepwise Transition Approach

Step 1 — Confirm Patient Can Eat

If not eating:continue IV insulin with dextrose

Step 2 — Calculate Total Daily Insulin Dose (TDD)

If Patient Already Uses Insulin

Resume home regimen if:previously controlled/reliable adherence

Adjust if needed.

If Newly Diagnosed Diabetes or Unknown Dose

Typical starting dose:

Step 3 — Divide into Basal and Prandial Insulin

Basal-Bolus Regimen

Typical:

• 50% basal
• 50% prandial

Example (35 units/day):

Basal Insulin Options

• Glargine,Detemir,NPH Insulin

Prandial Insulin Options

• Lispro/Aspart/Regular Insulin

Complications of DKA

Acute Complications

Cerebral Edema

Most feared complication in children.

Risk Factors

• Rapid osmolar correction,Severe acidosis,Young age
• Excess fluids

Features

• Headache
• Bradycardia
• Altered consciousness
• Hypertension

Management

• Mannitol
• Hypertonic saline
• ICU care