How to initiate Mixtard (insulin) therapy in a patient with high hyperglycemia and no prior history of insulin use?

Initiating Mixtard in High Hyperglycemia

Start Mixtard at 0.3-0.5 units/kg/day divided as two-thirds in the morning and one-third in the evening, with the morning dose given 30 minutes before breakfast and the evening dose before dinner, titrating by 2-4 units every 3 days based on fasting and pre-dinner glucose levels. 1

Initial Dosing Strategy

For insulin-naive patients with severe hyperglycemia (glucose >300 mg/dL or HbA1c >10%), begin with 0.4-0.5 units/kg/day total daily dose. 1, 2

• Calculate total daily dose: For a 70 kg patient, this equals 28-35 units/day 2
• Distribute as 2/3 of total dose in the morning (approximately 20-24 units) and 1/3 in the evening (approximately 10-12 units) 1, 2
• Administer morning dose 30 minutes before breakfast to allow the regular insulin component to align with postprandial glucose rise 3, 2
• Give evening dose 30 minutes before dinner 2

Titration Protocol

Increase doses by 2-4 units every 3 days based on glucose patterns, targeting fasting glucose 80-130 mg/dL and pre-dinner glucose <180 mg/dL. 1

• If fasting glucose remains >150 mg/dL, increase the evening dose by 2-4 units 1, 4
• If pre-dinner glucose is elevated, increase the morning dose by 2-4 units 1
• Monitor for hypoglycemia during titration, particularly nocturnal hypoglycemia with NPH-containing formulations like Mixtard 1, 5

Critical Monitoring Requirements

Check fasting and pre-dinner glucose daily during the first 2 weeks of titration. 1, 2

• Perform blood glucose monitoring before each meal and at bedtime initially 1, 2
• Add 2-hour postprandial checks if HbA1c remains >7.5% despite adequate fasting control 2
• Reassess HbA1c every 3 months 6
• Track all hypoglycemic episodes (glucose ≤70 mg/dL) 1, 5

Patient Education Essentials

Provide "survival skills" education covering injection technique, timing relative to meals, hypoglycemia recognition and treatment, and sick day management before hospital discharge. 1, 2

• Teach proper injection technique using 4-6 mm needles to avoid intramuscular injection 2
• Emphasize site rotation to prevent lipohypertrophy, which distorts insulin absorption 2
• Instruct on treating hypoglycemia with 15-20 grams of fast-acting carbohydrate 5
• Explain that insulin doses must be adjusted during acute illness 1

When to Consider Alternative Approaches

If the patient has cardiovascular disease, heart failure, or chronic kidney disease, strongly consider adding a GLP-1 receptor agonist before or alongside insulin initiation to provide cardiorenal protection beyond glucose lowering. 1, 7

• GLP-1 RAs reduce hypoglycemia risk and weight gain compared to insulin intensification alone 1
• They allow lower insulin doses to achieve the same glycemic targets 1, 7
• Consider fixed-ratio combinations of basal insulin with GLP-1 RA if available and affordable 1

Common Pitfalls to Avoid

Do not use sliding-scale insulin as monotherapy—it is ineffective and increases hypoglycemia risk. 1, 4

• Avoid delaying insulin initiation when glucose consistently exceeds 300 mg/dL, as prolonged severe hyperglycemia causes irreversible complications 7
• Do not continue ineffective oral therapy for months hoping for spontaneous improvement 7
• Never inject into areas of lipohypertrophy, as this causes erratic absorption 2
• Do not abruptly discontinue metformin when starting insulin, as the combination reduces weight gain and insulin requirements 2

Special Circumstances Requiring Modification

In patients receiving glucocorticoids, increase the morning Mixtard dose by 50-100% to cover daytime hyperglycemia, as steroids cause disproportionate afternoon and evening glucose elevation. 1

• For dexamethasone specifically, consider switching to NPH twice daily at 0.3 units/kg/day total (2/3 morning, 1/3 evening) for easier dose adjustment 1
• Reduce insulin doses rapidly when steroids are discontinued to prevent severe hypoglycemia 1

For hospitalized patients on enteral nutrition, switch from Mixtard to NPH every 8-12 hours with correctional rapid-acting insulin every 4-6 hours, as continuous feeding requires different insulin coverage. 1