What are the causes of hyperglycemia in patients?

Causes of Hyperglycemia in Inpatients

Hyperglycemia in hospitalized patients is primarily caused by insulin deficiency, insulin resistance, or a combination of both mechanisms, resulting from various underlying conditions and iatrogenic factors.

Primary Pathophysiological Mechanisms

Hyperglycemia results from two fundamental mechanisms 1:

1. Deficient insulin secretion - Inadequate insulin production by pancreatic β-cells
2. Insulin resistance - Diminished tissue response to insulin action

These mechanisms often coexist in the same patient, making it difficult to determine which is the primary cause of hyperglycemia 1.

Major Categories of Inpatient Hyperglycemia

1. Pre-existing Diabetes

• Type 1 Diabetes: Absolute insulin deficiency due to autoimmune destruction of β-cells 1
• Type 2 Diabetes: Combination of insulin resistance and inadequate compensatory insulin secretion 1
• Pancreatic Diabetes: Secondary to pancreatic diseases, featuring severe insulinopenia 1

2. Stress Hyperglycemia

Defined as transient hyperglycemia (blood glucose >180 mg/dL or 10 mmol/L) in previously non-diabetic patients during acute illness or invasive procedures 1. Key features:

• Returns to normal (<126 mg/dL or 7 mmol/L) after removal of stressor
• Occurs in patients with HbA1c <6.5% 1
• Prevalence varies between 30-80% depending on type of surgery 1

Mechanisms of Stress Hyperglycemia:

• Peripheral insulin resistance (primary mechanism) 1
• Increased endogenous glucose production 1
• Enhanced renal glucose reabsorption 1
• Decreased glucose clearance 1
• Release of stress hormones (glucagon, cortisol, catecholamines) 1
• Inflammatory mediators (interleukin 1 and 6) 1

3. Medication-Induced Hyperglycemia

Multiple medications can cause or exacerbate hyperglycemia through various mechanisms 2:

• Glucocorticoids: Most common cause of drug-induced hyperglycemia in hospitalized patients, especially at high doses 3, 2
• Antihypertensives: Particularly thiazide diuretics and certain beta-blockers 2
• Antipsychotics: Second-generation antipsychotics cause insulin resistance 2
• Immunosuppressants: Including calcineurin inhibitors (decrease insulin secretion) 2
• Chemotherapeutic agents: Certain agents carry higher risk 2
• Anti-infectives: Especially fluoroquinolones at high doses 2
• Antiretrovirals: Particularly protease inhibitors 2
• Sympathomimetics: Beta-adrenergic stimulants can cause hyperglycemia 2
• Statins: Diabetogenic effect varies by type and dose 2

4. Hyperglycemic Crises

Severe, acute hyperglycemic states requiring immediate intervention 1, 4:

• Diabetic Ketoacidosis (DKA): Characterized by hyperglycemia, ketosis, and metabolic acidosis 1
• Hyperosmolar Hyperglycemic State (HHS): Extreme hyperglycemia (>600 mg/dL), hyperosmolarity, severe dehydration, minimal ketosis 4

Common Precipitating Factors in Inpatients

1. Infection: Most common precipitating factor for hyperglycemic crises 1, 5
2. Inadequate insulin therapy: Discontinuation or insufficient insulin in established diabetes 1
3. New-onset diabetes: Particularly in elderly individuals 1
4. Surgical stress: Causes insulin resistance that may last several days 1
5. Nutritional factors:
   • Prolonged fasting (increases neoglucogenesis) 1
   • Inappropriate TPN administration 6
   • Unexpected changes in nutritional intake 6
6. Medical procedures: Especially cardiac surgery with extracorporeal circulation 1
7. Inadequate prescribing practices:
   • Exclusive use of sliding-scale insulin regimens 6
   • Failure to adjust antidiabetic medications 6
   • Provider unwillingness to take responsibility for diabetes management 6
8. Comorbidities:
   • Acute pancreatitis 1
   • Myocardial infarction 1
   • Stroke 1
   • Trauma 1
   • Extensive burns 1
   • Liver disease 1

Special Considerations in Specific Patient Populations

Oncology Patients

• Higher risk due to frequent exposure to glucocorticoids, immunosuppressants, and TPN 7
• Hematologic malignancies particularly at risk due to treatment regimens 7
• HbA1c may be inaccurate due to disordered hematopoiesis and frequent transfusions 7

Elderly Patients

• More prone to hyperglycemia due to higher rates of comorbidities 1
• May have undiagnosed pre-existing diabetes 1
• Often have failure of regulatory mechanisms, especially in stress situations 1

Clinical Implications

Uncontrolled hyperglycemia in hospitalized patients is associated with:

• Increased risk of infections 5
• Higher mortality rates 1
• Impaired wound healing 1
• Endothelial dysfunction 1
• Decreased phagocytic activity of neutrophils 1
• Increased length of hospital stay 1

Practical Approach to Identifying Causes

1. Determine if hyperglycemia is new-onset or pre-existing:

   • Check HbA1c (if reliable) to distinguish between stress hyperglycemia and undiagnosed diabetes 1
   • Review prior medical records for diabetes history

2. Evaluate for precipitating factors:

   • Current medications, especially glucocorticoids
   • Presence of infection or other acute stressors
   • Recent surgical procedures
   • Changes in nutritional status

3. Assess for signs of hyperglycemic crisis:

   • Mental status changes
   • Dehydration
   • Presence of ketones in urine or blood
   • Acidosis

Understanding the specific cause of hyperglycemia in hospitalized patients is essential for appropriate management and prevention of complications.