What is the initial workup and management for a patient presenting with hyperglycemia?

Initial Workup for Hyperglycemia

For a patient presenting with hyperglycemia, immediately assess the severity of presentation and metabolic status to determine if this is a medical emergency requiring insulin therapy versus stable hyperglycemia that can be managed more conservatively. 1

Immediate Clinical Assessment

Critical Questions to Ask

• Symptoms of severe hyperglycemia or ketoacidosis: polyuria, polydipsia, nocturia, unintentional weight loss, nausea, vomiting, abdominal pain, altered mental status, or Kussmaul respirations 1, 2
• Duration and onset of symptoms: acute versus chronic presentation helps differentiate new-onset diabetes from decompensation of known disease 1
• Medication history: current use of corticosteroids (prednisone, dexamethasone), immune checkpoint inhibitors, SGLT2 inhibitors, or other diabetogenic medications 1
• Diabetes history: known type 1 or type 2 diabetes, previous insulin use, typical glucose control, and recent HbA1c values 1
• Precipitating factors: recent infections, acute illness, medication changes, alcohol or illicit drug use, chemotherapy exposure, or treatment nonadherence 1, 2
• Risk factors for diabetes: family history, obesity, hypertension, cardiovascular disease, metabolic syndrome 1

Physical Examination Priorities

• Volume status assessment: signs of dehydration (dry mucous membranes, poor skin turgor, tachycardia, hypotension) are critical as hyperosmolar states require aggressive fluid resuscitation 2
• Neurologic examination: level of consciousness ranging from alert to lethargy to coma indicates severity of hyperosmolarity 2
• Orthostatic vital signs: assess for volume depletion 1
• Weight and body mass index: essential for medication dosing and risk stratification 1
• Signs of infection: fever, focal findings suggesting pneumonia, urinary tract infection, or other precipitating infections 2, 3

Laboratory Workup

Immediate Laboratory Tests (Stat)

• Point-of-care glucose: establishes severity immediately 1
• Serum or urine ketones: differentiates diabetic ketoacidosis from hyperosmolar hyperglycemic state 1, 2
• Basic metabolic panel: sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine to assess for metabolic acidosis, electrolyte disturbances, and renal function 1, 2
• Venous or arterial blood gas: if ketones present or altered mental status to quantify acidosis 1
• Serum osmolality: calculated or measured osmolality >320 mOsm/kg suggests hyperosmolar hyperglycemic state 2

Additional Initial Laboratory Tests

• Complete blood count: evaluate for infection or stress response 1
• HbA1c: provides 2-3 month glycemic history and helps differentiate acute versus chronic hyperglycemia 1
• Lipid profile: assess cardiovascular risk 1
• Liver function tests: baseline assessment and to identify hepatic dysfunction 1
• Thyroid-stimulating hormone: thyroid disease can affect glucose metabolism 1
• Urinalysis: screen for infection, proteinuria, and ketonuria 1
• Fasting lipase: if on immune checkpoint inhibitors or if pancreatitis suspected 1

Specialized Testing Based on Context

• Pancreatic autoantibodies (GAD65, IA-2, ZnT8, insulin autoantibodies): if suspicion for autoimmune diabetes, particularly in patients on immune checkpoint inhibitors or youth with obesity 1
• C-peptide level: helps differentiate type 1 from type 2 diabetes in ambiguous cases 1

Risk Stratification and Severity Assessment

Emergency/High-Risk Presentation (Requires Immediate Insulin)

• Blood glucose ≥300-350 mg/dL (16.7-19.4 mmol/L) with symptoms 1
• Any ketoacidosis or significant ketosis 1
• Blood glucose ≥600 mg/dL (33.3 mmol/L): assess for hyperosmolar hyperglycemic state 1, 2
• HbA1c ≥10-12% with catabolic features (weight loss, muscle wasting) 1
• Altered mental status or profound dehydration 2

Moderate-Risk Presentation

• Blood glucose ≥250 mg/dL (13.9 mmol/L) or HbA1c ≥8.5% (69 mmol/mol) without acidosis but with symptoms (polyuria, polydipsia, nocturia, weight loss) 1
• Recent corticosteroid initiation or dose increase: monitor within 2 weeks and every 4 weeks thereafter 1
• On immune checkpoint inhibitors with new hyperglycemia: requires close monitoring for progression to autoimmune diabetes 1

Low-Risk/Stable Presentation

• Fasting glucose <7 mmol/L (126 mg/dL), random glucose ≤11 mmol/L (198 mg/dL), and HbA1c <6.5% (48 mmol/mol): continue routine monitoring 1
• HbA1c <8.5% (69 mmol/mol) without symptoms or acidosis: can initiate oral therapy 1

Context-Specific Considerations

Corticosteroid-Induced Hyperglycemia

• Timing of hyperglycemia: prednisone causes peak hyperglycemia 8 hours post-dose (late morning/afternoon pattern); dexamethasone peaks at 7-9 hours 1
• Dose-dependent effect: higher steroid doses correlate with greater hyperglycemia 1
• Diagnosis: two abnormal tests (random glucose ≥11.1 mmol/L on different occasions and/or HbA1c ≥6.5%) plus corticosteroid use 1

Immune Checkpoint Inhibitor Therapy

• Median onset: 12 weeks after ICI initiation, but can occur years later 1
• High-risk features: pre-existing type 2 diabetes, concurrent SGLT2 inhibitor use (increased euglycemic DKA risk), elevated lipase 1
• Monitoring duration: while on treatment and for 12 months post-completion 1
• SGLT2 inhibitor caution: re-educate about euglycemic DKA risk; ensure patient can measure ketones; consider discontinuation if ketone monitoring not feasible 1

Youth with Obesity

• Diagnostic uncertainty: substantial overlap between type 1 and type 2 diabetes presentations; up to 25% of youth with type 2 diabetes present with ketoacidosis 1
• Autoantibody testing: essential to guide long-term management once metabolic stabilization achieved 1

Common Pitfalls to Avoid

• Underestimating severity: fasting glucose alone may miss postprandial hyperglycemia, particularly with corticosteroids; 2-hour postprandial or random glucose is more sensitive 1
• Delaying insulin in severe hyperglycemia: glucose ≥300 mg/dL with symptoms or any ketoacidosis requires immediate insulin regardless of diabetes type 1
• Missing euglycemic DKA: patients on SGLT2 inhibitors can develop ketoacidosis with glucose <250 mg/dL; always check ketones if on these agents 1
• Inadequate infection screening: infections are the most common precipitant of hyperglycemic crises and must be identified and treated 2, 3
• Failing to adjust diabetes regimen with steroid changes: steroid dose adjustments necessitate corresponding changes in diabetes treatment 1