Causes of Hyperglycemic Crisis
Infection is the most common precipitating factor for both diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS), followed by inadequate insulin therapy, with other important causes including myocardial infarction, stroke, pancreatitis, and certain medications. 1
Primary Precipitating Factors
Most Common Causes
Infection stands as the leading precipitant across all hyperglycemic crises 1. Studies confirm this remains the most frequent trigger, with one series showing infections in 73.5% of cases 2. Importantly, patients may be normothermic or even hypothermic despite active infection due to peripheral vasodilation, so absence of fever does not exclude infection 1. When infection leads to death in hyperglycemic crisis, mortality rates are particularly high 3.
Inadequate insulin therapy represents the second major category:
- New-onset type 1 diabetes (often the initial presentation)
- Discontinuation of insulin in established type 1 diabetes
- Non-compliance with prescribed insulin regimens 1
Non-compliance accounted for 42.2% of cases in one study, though notably, no deaths occurred when non-compliance was the sole precipitant 2, 3.
Cardiovascular and Cerebrovascular Events
Acute cardiovascular events are critical precipitants:
- Myocardial infarction
- Cerebrovascular accident (stroke) 1
Cerebrovascular disease carries particularly high mortality risk—all patients with CVD who died in one series were unconscious on presentation 3. This underscores the importance of aggressive neurological monitoring.
Other Medical Precipitants
Additional established causes include:
- Pancreatitis (both cause and consequence of hyperglycemic crisis)
- Trauma
- Alcohol abuse 1
Medication-Induced Hyperglycemic Crisis
Drugs affecting carbohydrate metabolism can precipitate both DKA and HHS 1:
- Corticosteroids (most common drug class)
- Thiazide diuretics
- Sympathomimetic agents (e.g., dobutamine, terbutaline)
High-Risk Populations
Elderly and Institutionalized Patients
Elderly individuals are at particular risk for HHS, especially:
- Residents of chronic care facilities
- Those with new-onset diabetes who are unaware of hyperglycemia
- Patients unable to access fluids independently when hyperglycemic 1
This population often develops HHS over days to weeks, unlike the more rapid evolution (typically 24 hours) seen in DKA 1.
Emerging Considerations
COVID-19 infection has been identified as a precipitant of acute hyperglycemic crises, with patients with diabetes showing higher mortality and worse prognosis 4. This represents an important contemporary cause requiring intensive monitoring.
Clinical Pitfalls
Common diagnostic errors to avoid:
- Assuming fever must be present with infection—hypothermia is actually a poor prognostic sign 1
- Missing cerebrovascular events in obtunded patients—CVD carries very high mortality 3
- Overlooking medication review—corticosteroids and thiazides are frequently prescribed
- Failing to recognize that HHS evolves more slowly than DKA, potentially delaying diagnosis in elderly patients 1
The pathophysiology underlying all these precipitants involves triggering a state of relative or absolute insulin deficiency combined with elevated counterregulatory hormones (glucagon, catecholamines, cortisol, growth hormone), leading to the metabolic derangements characteristic of hyperglycemic crisis 1.