What are the causes of Diabetic Ketoacidosis (DKA)?

From the Guidelines

Diabetic ketoacidosis (DKA) is primarily caused by insulin deficiency combined with increased levels of counter-regulatory hormones, as evidenced by the most recent study 1. The main causes of DKA include:

• Undiagnosed type 1 diabetes
• Insulin therapy omission in known diabetics
• Acute illness or stress When patients with diabetes miss insulin doses or take inadequate amounts, their bodies cannot use glucose for energy, leading to fat breakdown and ketone production. Infections, particularly urinary tract infections and pneumonia, are common triggers as they increase stress hormones that counteract insulin. Other precipitating factors include:
• Myocardial infarction
• Stroke
• Pancreatitis
• Trauma
• Surgery
• Medications (especially corticosteroids, thiazide diuretics, and certain antipsychotics)
• Alcohol abuse
• Drug use (particularly cocaine) Insulin pump failure can also precipitate DKA in patients using these devices. Physiologically, the insulin deficiency prevents glucose uptake by cells while simultaneously increasing gluconeogenesis and glycogenolysis in the liver, resulting in hyperglycemia, as described in 1. The body then shifts to fat metabolism, producing ketone bodies (acetoacetate, beta-hydroxybutyrate, and acetone) that accumulate and cause metabolic acidosis, leading to the classic symptoms of DKA including polyuria, polydipsia, nausea, vomiting, abdominal pain, and altered mental status. Recent studies, such as 1, have shown that individualization of treatment based on a careful clinical and laboratory assessment is needed, and management goals include restoration of circulatory volume and tissue perfusion, resolution of ketoacidosis, and correction of electrolyte imbalance and acidosis. It is also essential to treat any correctable underlying cause of DKA, such as sepsis, myocardial infarction, or stroke, as recommended in 1.

From the FDA Drug Label

Hyperglycemia (too much glucose in the blood) may develop if your body has too little insulin Hyperglycemia can be brought about by any of the following: Omitting your insulin or taking less than your doctor has prescribed. Eating significantly more than your meal plan suggests. Developing a fever, infection, or other significant stressful situation. In patients with type 1 or insulin-dependent diabetes, prolonged hyperglycemia can result in DKA (a life-threatening emergency) Hyperglycemia, diabetic ketoacidosis, or hyperosmolar coma may develop if the patient takes less Humulin R U-100 than needed to control blood glucose levels This could be due to increases in insulin demand during illness or infection, neglect of diet, omission or improper administration of prescribed insulin doses or use of drugs that affect glucose metabolism or insulin sensitivity.

The causes of Diabetic Ketoacidosis (DKA) include:

• Omitting insulin or taking less than prescribed
• Eating more than the meal plan suggests
• Fever, infection, or stressful situations
• Increases in insulin demand during illness or infection
• Neglect of diet
• Omission or improper administration of prescribed insulin doses
• Use of drugs that affect glucose metabolism or insulin sensitivity 2 2

From the Research

Causes of Diabetic Ketoacidosis (DKA)

• Infection is the most common precipitating cause for DKA, occurring in 30-50% of cases, with urinary tract infection and pneumonia being the most common infections 3
• Other precipitating causes include intercurrent illnesses (e.g. surgery, trauma, myocardial ischemia, pancreatitis), psychological stress, and non-compliance with insulin therapy 3
• Insulin non-adherence is a common precipitating factor for developing DKA, seen in 51.2% of cases 4
• Pump/tubing related issues are a common cause of DKA in insulin pump users, accounting for 55% of cases 4
• Social factors, education, and insulin pump malfunction may also play a role in DKA etiology in young adults with type 1 diabetes, especially in insulin pump users 4
• Prior DKA, baseline hemoglobin A1C level, baseline creatinine level, use of medications for dementia, and baseline bicarbonate level are strong predictors of DKA in patients taking SGLT2 inhibitors 5
• Use of dementia medications, prior intracranial hemorrhage, prior diagnosis of hypoglycemia, prior DKA, digoxin use, high baseline hemoglobin A1C, and low baseline bicarbonate are associated with an increased risk of hospitalization for DKA in patients taking SGLT2 inhibitors 5
• SGLT2 inhibitors can increase the risk of euglycaemic diabetic ketoacidosis, although this is a rare adverse effect 6