Hyperglycemia Management
Diagnostic Evaluation
Immediately assess for diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) in any patient with severe hyperglycemia. Obtain venous blood gases, serum electrolytes, blood urea nitrogen, creatinine, and urine or blood ketones without delay 1. DKA is defined by glucose >250 mg/dL, venous pH <7.3, bicarbonate <15 mEq/L, and moderate ketonuria or ketonemia 1, 2. HHS presents with glucose >600 mg/dL, venous pH >7.3, bicarbonate >15 mEq/L, and altered mental status or severe dehydration 1, 2.
Check for precipitating factors including infection, insulin omission, undiagnosed diabetes, and substance abuse 2. Monitor for symptoms such as polyuria, polydipsia, fatigue, Kussmaul respiration, altered mental status, or severe dehydration 1.
Acute Management of DKA/HHS
Fluid Resuscitation
Initiate aggressive isotonic saline resuscitation immediately for all patients with DKA or HHS 1, 3. Adjust fluid composition based on serum sodium and hemodynamic status 1.
Insulin Therapy
Start continuous IV insulin infusion at 0.1 units/kg/hour for severe hyperglycemia with DKA 1, 3. Target a glucose decline of 50-75 mg/dL per hour until glucose reaches 200-250 mg/dL 1. Continue IV insulin until pH >7.3, bicarbonate >18 mEq/L, and anion gap <12 mEq/L are achieved 1.
For mild DKA without severe acidosis (pH >7.0), subcutaneous rapid-acting insulin may be considered as an alternative to IV insulin in select cases 3.
Electrolyte Management
Add 20-30 mEq of potassium (approximately 2/3 KCl + 1/3 KPO₄) to each liter of IV fluid when serum potassium falls below 5.5 mEq/L, provided urine output is adequate 1. Monitor serum electrolytes, glucose, BUN, creatinine, osmolality, and venous pH every 2-4 hours 1, 3.
Transition to Subcutaneous Insulin
Administer the first subcutaneous basal insulin dose 2-4 hours before stopping the IV insulin infusion to prevent rebound hyperglycemia and recurrent ketoacidosis 4, 3. Adding 0.15-0.30 units/kg of basal insulin analog during the IV infusion can shorten infusion duration and further prevent rebound hyperglycemia 4.
A common pitfall is premature termination of IV insulin therapy or insufficient timing/dosing of subcutaneous insulin before discontinuation of IV insulin 3.
Outpatient Insulin Initiation for Severe Hyperglycemia
For asymptomatic patients with severe hyperglycemia (glucose >300-350 mg/dL or HbA1c ≥9%) without ketoacidosis or severe dehydration, initiate insulin therapy as an outpatient with a total daily dose of 0.3-0.5 units/kg/day 5, 1.
Basal-Bolus Regimen
Use a basal-bolus insulin regimen with 50% of the total daily dose given as basal insulin (glargine, detemir, or degludec) once daily and 50% as prandial insulin (lispro, aspart, or glulisine) divided among three meals 5, 4, 1. For a 70 kg patient, this translates to approximately 21-35 units/day total, with 11-18 units as basal and 11-18 units as prandial (approximately 4-6 units per meal) 4.
Administer rapid-acting insulin 0-15 minutes before meals for optimal postprandial control 5, 4.
Titration Protocol
Basal insulin: Increase by 2 units every 3 days if fasting glucose is 140-179 mg/dL; increase by 4 units every 3 days if fasting glucose ≥180 mg/dL 5, 4. Target fasting glucose 80-130 mg/dL 5, 4.
Prandial insulin: Increase each meal dose by 1-2 units (approximately 10-15%) every 3 days based on 2-hour postprandial glucose readings 5, 4. Target postprandial glucose <180 mg/dL 5, 4.
If hypoglycemia (<70 mg/dL) occurs, reduce the implicated insulin dose by 10-20% immediately 5, 4.
Long-Term Pharmacologic Therapy
Foundation Therapy
Continue metformin at maximum tolerated dose (up to 2000-2550 mg daily) when initiating or intensifying insulin therapy unless contraindicated 5, 4. Metformin reduces total insulin requirements by 20-30% and provides superior glycemic control compared to insulin alone 4.
Advancing Beyond Basal Insulin
When basal insulin exceeds 0.5 units/kg/day and approaches 1.0 units/kg/day without achieving glycemic targets, add prandial insulin or a GLP-1 receptor agonist rather than continuing to escalate basal insulin alone 5, 4. This prevents "overbasalization" characterized by basal dose >0.5 units/kg/day, bedtime-to-morning glucose differential ≥50 mg/dL, hypoglycemia, and high glucose variability 5, 4.
GLP-1 Receptor Agonists
Consider adding a GLP-1 receptor agonist when basal insulin has been optimized but HbA1c remains above target after 3-6 months 5. GLP-1 RAs provide 1-2% HbA1c reduction with lower hypoglycemia risk and weight loss rather than weight gain 5. If cardiovascular disease is present, select a GLP-1 RA with proven cardiovascular benefit 5.
SGLT2 Inhibitors
For patients with established cardiovascular disease, heart failure, or chronic kidney disease, add an SGLT2 inhibitor for cardiovascular and renal protection in addition to glucose-lowering effects 5.
Monitoring Requirements
Check fasting glucose daily during insulin titration 5, 4, 1. For hospitalized patients eating regular meals, measure capillary glucose before each meal and at bedtime 4, 6. For patients with poor oral intake or NPO status, check glucose every 4-6 hours 4, 6.
Reassess HbA1c every 3 months during intensive titration and until stable glycemic control is achieved 5, 1.
Critical Pitfalls to Avoid
Never use sliding-scale insulin as monotherapy—major diabetes guidelines condemn this approach as it reacts to hyperglycemia rather than preventing it, leading to dangerous glucose fluctuations 4, 6, 7. Only approximately 38% of patients on sliding-scale alone achieve mean glucose <140 mg/dL versus 68% with scheduled basal-bolus therapy 4.
Do not delay insulin initiation in patients not achieving glycemic goals with oral medications, as this prolongs hyperglycemia exposure and increases complication risk 5, 4.
Do not discontinue metformin when starting insulin unless contraindicated, as this leads to higher insulin requirements and more weight gain 5, 4.
Never give rapid-acting insulin at bedtime as a sole correction dose, as this markedly raises nocturnal hypoglycemia risk 5, 4.
Do not continue escalating basal insulin beyond 0.5-1.0 units/kg/day without addressing postprandial hyperglycemia, as this leads to overbasalization with increased hypoglycemia risk and suboptimal control 5, 4.
Special Populations
Hospitalized Patients
For non-critically ill hospitalized patients, target glucose 140-180 mg/dL 4, 6, 7. Use a basal-bolus regimen with total dose 0.3-0.5 units/kg/day (50% basal, 50% prandial) for patients eating regular meals 4. For high-risk patients (age >65 years, renal impairment, poor oral intake), start with 0.1-0.25 units/kg/day 4.
Older Adults
In older adults receiving palliative care, simplify regimens by focusing on comfort and preventing symptomatic hyperglycemia (>250 mg/dL) or hypoglycemia 5. Adjust insulin doses every 2 weeks based on finger-stick glucose testing 5.
Pediatric Patients
For youth with type 2 diabetes presenting with marked hyperglycemia (blood glucose ≥250 mg/dL, HbA1c ≥8.5%) without acidosis, treat initially with basal insulin while metformin is initiated and titrated 5. In patients with ketosis/ketoacidosis, initiate subcutaneous or IV insulin to rapidly correct hyperglycemia and metabolic derangement 5.