What are the risk factors for diabetic ketoacidosis (DKA)?

Risk Factors for Diabetic Ketoacidosis

Infection is the single most common precipitating factor for DKA, occurring in 30-50% of cases, with urinary tract infections and pneumonia being the most frequent culprits. 1, 2, 3, 4

Core Pathophysiologic Mechanism

DKA develops from absolute or relative insulin deficiency combined with elevated counterregulatory hormones (glucagon, catecholamines, cortisol, growth hormone), which together trigger uncontrolled lipolysis and ketogenesis. 2 This hormonal imbalance leads to impaired peripheral glucose utilization and increased hepatic glucose production, resulting in the characteristic hyperglycemia and metabolic acidosis. 1, 2

Most Common Precipitating Factors

Infection (30-50% of cases)

• Urinary tract infections and pneumonia account for the majority of infection-related DKA. 1, 3, 4
• Patients may present with normothermia or even hypothermia despite serious infection; hypothermia is a poor prognostic sign. 2
• Acute febrile illness increases insulin requirements through stress hormone elevation. 2

Insulin-Related Issues

• Insulin omission or inadequate dosing is the most common cause of recurrent DKA in established diabetes, particularly in patients with psychiatric illness, those from single-parent homes, and underinsured individuals. 2
• Psychological problems and financial constraints are leading causes of insulin non-compliance. 2
• Patients should never discontinue basal insulin, even when not eating, as this can precipitate DKA within 4-10 hours. 1, 2

New-Onset Diabetes

• First presentation of type 1 diabetes, particularly in children and adolescents, frequently manifests as DKA. 1, 2
• Up to 25% of newly diagnosed type 1 diabetes patients present in DKA. 1

SGLT2 Inhibitor-Associated DKA

SGLT2 inhibitors are now a leading cause of DKA, including euglycemic DKA (glucose <200 mg/dL), with an incidence of 0.6-4.9 events per 1,000 patient-years. 1, 5, 2 The relative risk is 2.46 (95% CI 1.16-5.21) compared to placebo in randomized controlled trials. 1, 5

Specific Risk Factors with SGLT2 Inhibitors:

• Very-low-carbohydrate diets and prolonged fasting 1, 5
• Dehydration and volume depletion 1, 5
• Excessive alcohol consumption 1, 5
• Presence of autoimmunity (latent autoimmune diabetes in adults misdiagnosed as type 2 diabetes) 1, 5
• Insulin dose reduction >20% when initiating SGLT2 inhibitors 5
• Acute illness or infection 1, 5

Critical prevention measure: Discontinue SGLT2 inhibitors at least 3 days before elective surgery or procedures requiring fasting. 5

Other Acute Medical Conditions

• Myocardial infarction can precipitate DKA through acute stress hormone elevation. 1, 2
• Cerebrovascular accidents are recognized triggers. 1, 2
• Acute pancreatitis may initiate DKA. 1, 2
• Trauma increases insulin requirements via the stress response. 1, 2
• Major surgery creates catabolic stress that can trigger DKA. 1, 3

Medication-Induced DKA

• Corticosteroids increase insulin resistance and counterregulatory hormones. 5, 2
• Atypical antipsychotics are associated with metabolic derangements leading to DKA. 5
• Thiazide diuretics may provoke hyperglycemic crises. 2
• Sympathomimetic agents (dobutamine, terbutaline) have been associated with DKA onset. 2

High-Risk Populations

Pregnancy

• Up to 2% of pregnancies with pregestational diabetes (most often type 1) are complicated by DKA. 1, 2
• Pregnant individuals may present with euglycemic DKA (glucose <200 mg/dL). 1
• The incidence in gestational diabetes is low (<0.1%). 1

Children and Adolescents

• Experience the fastest progression to DKA because β-cell destruction is most rapid in this age group. 2
• DKA rates among U.S. children and adolescents have risen dramatically over the past two decades. 2
• Those with eating disorders have higher frequency of recurrent DKA. 2

Elderly Patients

• Residents of chronic care facilities who become hyperglycemic and cannot access fluids are at elevated risk. 2
• Higher mortality rates are observed in elderly patients with DKA. 1

Socioeconomic Factors

• Urban African-Americans are at risk of discontinuing insulin due to economic barriers. 2
• Underinsured patients have higher rates of insulin omission. 2

Alcohol and Substance Use

• Alcohol abuse is a documented precipitating factor for both standard and euglycemic DKA. 1, 2
• Alcohol use combined with reduced food intake and liver dysfunction increases DKA risk. 1

Critical Prevention Strategies

• Educate patients on sick-day management: contact provider when blood glucose exceeds 300 mg/dL, use supplemental short-acting insulin, maintain liquid diet with carbohydrates and salt. 2
• Never stop basal insulin, even during illness or fasting. 1
• Temporarily discontinue SGLT2 inhibitors during acute illness, dehydration, or prolonged fasting. 5
• Counsel patients on SGLT2 inhibitors to seek immediate care for nausea, vomiting, abdominal pain, or generalized weakness. 5
• Address economic barriers to insulin access. 2
• Monitor for ketones (blood β-hydroxybutyrate preferred over urine) during high-risk situations. 5

Common Pitfalls to Avoid

• Do not assume normal body temperature rules out infection—patients with DKA can be normothermic or hypothermic despite serious infection. 2
• Do not reduce insulin doses by >20% when initiating SGLT2 inhibitors. 5
• Do not overlook autoimmunity in patients initially thought to have type 2 diabetes. 5, 2
• Do not restart SGLT2 inhibitors until the patient has been metabolically stable for 3-4 days after euglycemic DKA. 6