How should uncontrolled hyperglycemia be managed?

Management of Uncontrolled Hyperglycemia

For severely uncontrolled hyperglycemia (fasting glucose ≥250 mg/dL, random glucose consistently >300 mg/dL, HbA1c >10%, or presence of ketonuria), initiate insulin therapy immediately in combination with lifestyle intervention, as this is the treatment of choice to rapidly restore glycemic control and relieve catabolic symptoms. 1

Immediate Assessment and Risk Stratification

Severe Hyperglycemia Requiring Emergency Care

• Check for ketones immediately in any patient with glucose >300 mg/dL, as this may indicate diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS), both life-threatening conditions requiring immediate medical intervention 1, 2
• Evaluate for precipitating factors including infection, medication non-compliance, trauma, myocardial infarction, or stroke 2
• If blood glucose levels reach 600 mg/dL, evaluate immediately to rule out HHS and treat promptly with fluid and insulin therapy 2
• Measure serum electrolytes urgently if hyperosmolarity is suspected (>320 mosmol/L confirms HHS and mandates ICU-level care) 3

Laboratory Assessment

• Obtain arterial blood gas, complete blood count, electrolyte panel, blood glucose, urea, creatinine, and urinalysis for ketones 2
• Calculate effective osmolality using: 2[Na+ (mEq/L)] + glucose (mg/dL)/18 2
• Check HbA1c to determine duration of hyperglycemia and guide long-term management strategy 3

Emergency Treatment for Hyperglycemic Crisis

Fluid Resuscitation

• Start fluid replacement with 0.9% NaCl at 15-20 mL/kg/hour in the first hour 2
• Replace estimated fluid deficit over 24 hours, with osmolality decrease no more than 3 mOsm/kg/hour to prevent cerebral edema 2
• Ensure aggressive hydration with IV fluids if the patient cannot maintain oral intake 3

Insulin Therapy for Crisis

• Begin continuous intravenous insulin infusion at 0.1 units/kg/hour after excluding hypokalemia (K+ <3.3 mEq/L) 2
• If blood glucose does not decrease by at least 50 mg/dL in the first hour, double the insulin dose every hour until achieving a decrease of 50-75 mg/dL/hour 2
• Target blood glucose of 180-270 mg/dL within 24 hours 2
• For critically ill patients, maintain blood glucose between 140-180 mg/dL once insulin therapy is initiated 2

Monitoring During Crisis

• Monitor blood glucose every hour during the acute phase 2
• Monitor electrolytes, renal function, and level of consciousness every 2-4 hours 2
• Watch for signs of cerebral edema if glucose falls too rapidly 2

Non-Emergency Severe Hyperglycemia Management

Immediate Insulin Initiation

For patients with severe hyperglycemia but without DKA/HHS, start rapid-acting insulin analogue immediately at 4-10 units subcutaneously, even before full workup is complete, as delays worsen outcomes. 3

• Initiate basal-bolus insulin regimen with total daily dose of 0.4-0.5 units/kg/day, giving 50% as basal insulin and 50% as prandial insulin divided among meals 3
• For a 50 kg patient, this translates to approximately 10 units of basal insulin once daily plus 6-7 units of rapid-acting insulin divided before meals 3
• Never delay basal insulin even if oral intake is poor—reduce prandial doses but maintain basal coverage to prevent ketosis 3

Insulin Titration Protocol

• Increase basal insulin by 4 units every 3 days if fasting glucose remains ≥180 mg/dL, or by 2 units every 3 days if fasting glucose is 140-179 mg/dL 3
• Target fasting glucose of 80-130 mg/dL (4.4-7.2 mmol/L) as the primary endpoint for basal insulin titration 3
• If basal insulin exceeds 0.5 units/kg/day without achieving targets, add or intensify prandial insulin rather than continuing to escalate basal insulin alone 3

Stepwise Approach for Moderate Hyperglycemia (HbA1c 7-10%)

Initial Therapy

• Begin with lifestyle intervention and metformin as first-line therapy, which should remain part of the treatment regimen if no contraindications exist 1
• Patients who cannot take metformin may use α-glucosidase inhibitors or insulin secretagogues 1

Dual Therapy

When metformin alone fails to achieve HbA1c <7.0%, add one of the following 1:

• Insulin secretagogues
• α-glucosidase inhibitors
• DPP-4 inhibitors
• Thiazolidinediones (TZDs)
• SGLT2 inhibitors
• Basal insulin
• GLP-1 receptor agonists

Insulin plus metformin is particularly effective for lowering glycemia while limiting weight gain. 1

Triple Therapy

• When dual therapy fails to achieve target HbA1c, initiate combination of three drugs with different mechanisms of action 1
• Patients with uncontrolled blood glucose after triple therapy should proceed to multiple daily insulin injections (basal + prandial insulin or multiple daily injections of premixed insulin) 1
• When treating with multiple insulin injections, discontinue insulin secretagogues 1

Transition from Intravenous to Subcutaneous Insulin

• Transition from IV to subcutaneous insulin once the patient is stable with blood glucose <300 mg/dL and able to eat 2
• Administer basal insulin 2-4 hours before stopping intravenous insulin to prevent recurrence of ketoacidosis and rebound hyperglycemia 1
• Initial subcutaneous insulin dose should be 60-80% of the total daily dose of intravenous insulin 2
• Implement basal-bolus insulin regimen at total dose of 0.3-0.5 units/kg, split 50/50 between basal and bolus insulin 2

Glycemic Targets

Standard Targets

• HbA1c <7.0% for most patients 1
• Fasting blood glucose: 4.4-7.0 mmol/L (80-126 mg/dL) 1
• Non-fasting blood glucose: <10.0 mmol/L (180 mg/dL) 1

Individualized Targets

• More stringent HbA1c targets (<6.5%) are indicated for patients with short disease duration, long life expectancy, no complications, and no significant cardiovascular disease, without significant hypoglycemia risk 1
• Less stringent HbA1c goals (<8.0%) are indicated for patients with history of severe hypoglycemia, limited life expectancy, advanced complications, extensive comorbidities, or long-standing diabetes difficult to control despite comprehensive treatment 1

Critical Pitfalls to Avoid

• Do not delay insulin initiation while attempting to optimize oral agents—glucose >400 mg/dL with symptoms mandates immediate insulin therapy 3
• Do not rely solely on correction insulin (sliding scale) without scheduled basal and prandial insulin, as this leads to persistent hyperglycemia and increased complications 3
• Do not use bicarbonate routinely in DKA management, as it makes no difference in resolution of acidosis or time to discharge 1
• Never stop basal insulin even if patient is not eating—this prevents ketosis in insulin-deficient patients 3

Special Considerations

Perioperative Management

• Hold metformin on the day of surgery 1
• Discontinue SGLT2 inhibitors 3-4 days before surgery 1
• Give half of NPH dose or 75-80% doses of long-acting analog insulin on day of surgery 1
• Monitor blood glucose at least every 2-4 hours while patient takes nothing by mouth 1
• Target perioperative blood glucose 100-180 mg/dL (5.6-10.0 mmol/L) 1

Hospitalized Patients

• Basal-bolus insulin coverage is superior to correction-only insulin in noncardiac general surgery patients, with improved glycemic outcomes and lower rates of perioperative complications 1
• A physician with expertise in diabetes management should treat hospitalized patients with severe hyperglycemia 1

Follow-Up and Monitoring

• Reassess within 24-48 hours if managing as outpatient, or immediately if any signs of DKA/HHS develop 3
• Ensure follow-up with endocrinology or primary care within 1-2 weeks of discharge 2
• Persistent blood glucose readings above 300 mg/dL require immediate medical attention 2
• More frequent blood glucose monitoring is necessary during any stressful event (illness, trauma, surgery) that aggravates glycemic control 1