DKA – The Bane of Diabetics and a Pain for Doctors

Over the years, diabetes mellitus has undoubtedly become the most common non-communicable disease in developing countries.

Did you know that the term “diabetes mellitus” is derived from 2 different languages? Diabetes in Greek means “to pass”, and mellitus is Latin means “sweet”. Interestingly, the origin of the name comes from the fact that people with diabetes pass sweet urine (glycosuria).

Now, we might never be sure whether someone actually tasted the urine of a diabetic to figure it out. But, in ancient India, ants were used to diagnose diabetes mellitus! If ants gathered near unflushed toilet bowls or toward spilled urine, it was thought that the patient had diabetes.

Now, diabetes per se doesn’t cause much discomfort to the patient - it’s complications are the real culprits.

Long term complications are by far the most troublesome. BUT, they do not pose an immediate threat to the patient’s life.

There are THREE emergencies that can wreak havoc on a patient’s health due to diabetes mellitus. These complications are:

• Hypoglycemia
• Diabetic ketoacidosis (DKA)
• Hyperosmolar hyperglycemic state (HHS), and

We’ll take a close look at diabetic ketoacidosis in this article.

Causes of DKA

Before taking a look at the causes, let’s dissect the term - diabetic ketoacidosis. 

You must understand that ketone bodies are always present in the blood. Their levels are kept in check by insulin (mainly). 

In diabetes mellitus (mainly type I), the lack of insulin promotes ketogenesis (from fatty acids and amino acids). Ketosis, in turn, leads to acidosis.

So, the causes of ketoacidosis include:

• Diabetes mellitus - more commonly type I
• Starvation leading to increased fatty acid metabolism
• Conditions that directly increase the insulin requirement - infections, gastroenteritis, pancreatitis, and myocardial infarction.

Blame Physiology

Yes, we have no one else to blame for DKA but physiology. Let’s explore this.

Ketogenesis is the protective response of the body to save the brain. This is because, after glucose, ketones are the second-best alternative source of energy for the brain!

But ketones are meant to only be a temporary solution during starvation before the body’s insulin kicks in and releases glucose via glycogenolysis and gluconeogenesis.

In diabetics, however, the lack of insulin promotes prolonged ketogenesis, which is the basis for DKA. 

To summarise:

On one hand -

Insulin deficiency

↓

Leads to hyperglycemia (>300 mg/dL)

↓

Osmotic diuresis leading to loss of water and electrolytes (Na⁺, K⁺)

↓

Dehydration and rapid intravascular volume depletion with severe hypokalemia

And on the other hand - 

The lack of energy stimulates glucagon secretion from the pancreas

↓

This promotes gluconeogenesis and breakdown of free fatty acids leading to acidosis

↓

FFAs end up getting converted into ketones giving rise to hyperketonemia and consequent ketonuria

↓

The resultant metabolic acidosis contributes to the symptoms

A patient of DKA

How do you recognize a patient with DKA? 

The dictum is - Don’t rely on a history of diabetes mellitus. 

You see, DKA can cause, what we call, silent death. Meaning a previously healthy patient, with absolutely no symptoms or signs of diabetes mellitus, can present in DKA.
And a significant number of patients (close to a third) who die due to DKA may have never had a history of diabetes for you to even suspect DKA!

This shows the importance of regular physicals and watching out for specific danger signs.

The typical symptoms include:

• Abdominal pain
• Nausea, vomiting
• A history suggestive of the so-called triad of diabetes - polyuria, polydipsia, and polyphagia may/may not be present.

Signs that you have to look for in patients to suspect DKA include:

• Tachycardia
• Signs of dehydration and intravascular volume depletion (hypotension)
• Tachypnea with “deep-sighing” breaths - Kussmaul’s respirations.

Wisdom from Grand Wizard Zeo

“Tachypnea in these patients is basically a compensatory mechanism in order to wash-out the excess CO2 to contribute to compensatory respiratory alkalosis.”

Author: Sav vas

• Diffuse abdominal tenderness resembling peritonitis.
   
• Lethargy, cerebral edema, which might ultimately lead to diabetic coma.

Confirming your suspicion

Due to the sheer number of differential diagnoses, you can’t simply start the patient on insulin based on the examination findings. You have to confirm your suspicion using lab investigations (most importantly - urine ketones). 

When the patient presents to the emergency - the first complication that is most likely going to kill the patient is DEHYDRATION. So, the minute you see the symptoms and signs of DKA with dehydration and hypotension, EVERY SECOND COUNTS (tick-tock).

The logical steps would be to secure an IV while simultaneously performing capillary blood glucose (CBG) assessment (if help is available), immediately drawing blood for investigations and starting the patient on normal saline (NS) - all within a matter of minutes. 

Blood investigations and what to expect:

• Raised blood glucose (obviously!) usually > 250 - 300 mg/dL (hyperglycemia)
   
• Positive urine ketones (ketonuria)
   
• ABG findings:
  As expected, the patient is bound to be acidotic with a pH ranging from 6.9 to 7.2 (<7.3), with reduced serum bicarbonate ranging from 5 - 15 mEq/L and low pCO₂ (15 - 20 mmHg) due to respiratory compensation via tachypnea (Kussmaul’s breathing).
  The anion gap is high. 
   
• Serum electrolytes and serum beta-hydroxybutyrate:
  As mentioned before, osmotic diuresis causes both intravascular fluid loss as well as the loss of serum electrolytes leading to hyponatremia (mild ~ 130 mEq/L).
  
  Now, here’s the twist - hyperkalemia (5 - 8 mEq/L) occurs DESPITE depletion of total body potassium via urine. 
  This paradox occurs because acidosis leads to a shift of potassium from the intracellular to the extracellular compartment.
  
  Similarly, the patient will have hyperphosphatemia despite the fact that total body phosphate levels are generally depleted.
   
• CBC may reveal leukocytosis with or without an associated infection.
   
• Serum lipase and amylase may be elevated in some patients. Imaging may be essential if you strongly suspect pancreatitis

Wisdom from Grand Wizard Zeo

“Pancreatitis can also cause ketoacidosis that closely mimics DKA. This condition is termed pancreatic ketoacidosis or Kabadi syndrome.”

Classifying DKA patients

DKA patients are classified into mild, moderate, and severe, based on pH and beta-hydroxybutyrate levels.

Lab Investigation	Mild	Moderate	Severe
pH	7.25 - 7.30	7.0 - 7.24	< 7.0
BHB (mmol/L)	3 - 4	4 - 8	> 8

This classification is mainly to decide WHERE to treat the patient. Mild DKA patients can be managed in the emergency department, while moderate to severe patients may require ICU admission.

The Goals

Place the patient nil per oral (NPO).

The therapeutic goals of treating DKA include:

• Restoring plasma volume
• Reduce blood glucose
• Replenish electrolytes
• Correct acidosis, and of course
• Treat the precipitating factors

Restoring plasma volume

The logic is - to increase plasma volume but to make sure that the patient doesn’t go into hypoglycemia. 
The patient is rushed with NS and then put on maintenance ½ NS till the plasma glucose reaches 250 mg/dL following which he is placed on 5% dextrose (5D) and ½ NS maintenance.

Reducing blood glucose and replenishing electrolytes

The drug of choice would be regular insulin - an initial IV bolus of 0.1 U/kg, followed by continuous IV infusion of 0.1 U/kg/hour. BUT WAIT!

DO NOT start insulin before looking at the patient’s serum potassium levels. If the patient’s initial serum potassium level is below 3.5 mEq/L, replace the K⁺ levels before initiating insulin therapy. 

As mentioned before, the patient has hyperkalemia due to the extracellular shift - but the actual total body potassium is LOW.

Insulin itself can shift the extracellular potassium intracellularly, unmasking these dangerously low potassium levels. This puts the patient at a risk of dangerous arrhythmias and even cardiac arrest.

Thus, close monitoring of potassium and capillary blood glucose levels is a MUST for patients on continuous insulin infusions. 

Correcting acidosis using Soda bicarb - the last-ditch stand

This is a highly debatable topic, especially in mild DKA patients as clinical benefits are minimal. 

Primum non nocere - First, do no harm.

Rapid correction of acidosis can shift the potassium levels back into the intracellular compartment precipitating hypokalemia! Thus, in mild to moderate DKA, starting the patient on sodium bicarbonate is not advisable.

If the pH reduces < 7.0 (severe DKA), soda bicarb may be considered under careful monitoring. 

So, what now?

When the patient is stabilized with the resolution of acidosis, urine for ketones becomes negative, and blood glucose goal reaches the 150 - 200 mg/dL range - the patient can begin graded oral feeds as tolerated (starting with clear liquids).

In Summary

Mnemonic - D.K.A

References:

1. Harrison’s Principles of Internal Medicine 20th edition; Page no: 318
2. Current Medical Diagnosis & Treatment (CMDT) 2020; Page no: 1262 - 1265
3. https://www.ncbi.nlm.nih.gov/books/NBK551501/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085289/
5. https://insights.ovid.com/article/00000433-201209000-00001
6. https://www.ncbi.nlm.nih.gov/books/NBK470282/
7. https://www.ncbi.nlm.nih.gov/books/NBK470309/
8. https://journals.aace.com/doi/10.4158/1934-2403-21.10.1184

Author’s footnote

DKA is an important topic for various entrance exams, but you are sure to come across loads of DKA patients in your life as a doctor. So this is more of a “life-lesson” if you will.

From the entrance exam point of view, here are a couple of mnemonics to remember the causes of metabolic acidosis:

High Anion Gap Metabolic Acidosis (HAGMA) - M.U.D.P.I.L.E.S	Normal Anion Gap Metabolic Acidosis (NAGMA) - F.U.S.E.D C.A.R
Methanol	Fistula - pancreatic
Uremia (due to Renal failure)	Ureterosigmoidostomy
Diabetic ketoacidosis	Small bowel fistula
Paraldehyde	Extra chloride (due to hyperalimentation)
INH and Iron tablets	Diarrhea
Lactic acidosis	Carbonic anhydrase inhibitor (acetazolamide)
Ethylene glycol	Addison’s disease
Salicylates	Renal tubular acidosis

Feel free to click on the references for a more in-depth reading if you so desire.

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