Can sepsis (Systemic Inflammatory Response Syndrome) cause Diabetic Ketoacidosis (DKA)?

Can Sepsis Cause Diabetic Ketoacidosis (DKA)?

Yes, sepsis is a well-established precipitating factor for diabetic ketoacidosis (DKA) and is one of the most common triggers for this life-threatening metabolic complication. 1

Pathophysiological Mechanism

• Sepsis triggers a stress response that increases counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone) which oppose insulin action 1
• This hormonal imbalance leads to increased hepatic glucose production, impaired peripheral glucose utilization, and enhanced lipolysis with subsequent ketogenesis 1
• The inflammatory response in sepsis further exacerbates insulin resistance, contributing to hyperglycemia and ketone production 1
• Sepsis can cause a significant increase in plasma triglycerides and free fatty acids (up to four-fold), potentially overwhelming the body's ability to utilize them properly 1

Clinical Evidence

• According to the American Diabetes Association guidelines, infection is the most common precipitating factor in the development of DKA 1
• In a study of hyperglycemic emergencies, infections were identified as precipitants in 59% of cases 2
• Sepsis can trigger DKA in both previously diagnosed diabetics and can be the presenting feature of new-onset diabetes 3
• In some cases, sepsis may even induce ketoacidosis in non-diabetic patients under specific conditions of decreased metabolic function, a condition termed "septic ketoacidosis" 4

Specific Infections That Can Trigger DKA

• Pneumonia/bronchopneumonia is a common infectious trigger, as documented in case reports 3
• Urinary tract infections, soft tissue infections, and bacteremia can all precipitate DKA 5
• Methicillin-resistant Staphylococcus aureus (MRSA) infections have been specifically documented as triggers for DKA 5

Diagnostic Challenges

• The presence of sepsis can complicate the diagnosis of DKA due to overlapping clinical features 6
• Standard sepsis screening tools have limitations in predicting infections in DKA patients:
  • Sequential Organ Failure Assessment score ≥4 shows high specificity (82.28%) but limited sensitivity (46.77%) 6
  • Systemic Inflammatory Response Syndrome criteria ≥2 has good sensitivity (95.16%) but a high false-positive rate (84.28%) 6

Management Implications

• When sepsis is identified as the precipitating factor for DKA, treatment must address both conditions simultaneously 7
• Management includes:
  • Aggressive fluid resuscitation to restore circulatory volume and tissue perfusion 7
  • Insulin therapy to correct hyperglycemia and resolve ketoacidosis 7
  • Appropriate antibiotic therapy based on suspected source of infection 7
  • Close monitoring of electrolytes, particularly potassium 7
  • Identification and treatment of the underlying infection source 7

Prognostic Significance

• The presence of sepsis significantly worsens the prognosis of DKA 2
• Sepsis is an independent predictor of mortality in hyperglycemic emergencies 2
• Elevated serum creatinine (>1.2 mg/dL), co-morbidities, and sepsis are independent predictors of mortality in hyperglycemic emergencies 2

Clinical Pearls and Pitfalls

• DKA patients may be normothermic or even hypothermic despite having infection, primarily due to peripheral vasodilation 1
• Hypothermia, if present, is a poor prognostic sign in DKA patients with infection 1
• Abdominal pain in DKA patients may be either a result of the metabolic derangement or a sign of intra-abdominal infection requiring further evaluation 1
• In patients on SGLT2 inhibitors, sepsis can trigger euglycemic DKA, which is easily missed due to the absence of significant hyperglycemia 5

In conclusion, sepsis is not only capable of causing DKA but is one of the most common precipitating factors. Early recognition and aggressive management of both conditions are essential for improving outcomes.