Why is Mixtard (biphasic insulin) given 2/3 in the morning and 1/3 at night?

Why Mixtard (Biphasic Insulin) is Given in a 2/3 Morning and 1/3 Evening Distribution

The 2/3 morning and 1/3 evening distribution of Mixtard (biphasic insulin) is recommended because it matches the physiological insulin requirements throughout the day, with higher insulin needs during daytime activities and meals, and lower needs during nighttime rest periods. 1

Rationale for the 2/3:1/3 Distribution

• The 2/3 morning dose provides coverage for both breakfast and lunch, as well as daytime activities when insulin requirements are typically higher 1
• The 1/3 evening dose provides sufficient coverage for dinner and overnight basal needs without causing nocturnal hypoglycemia 1
• This distribution aligns with the body's natural diurnal variation in insulin sensitivity and glucose metabolism 1

Physiological Basis

• Daytime insulin requirements are higher due to:

  • Morning cortisol surge (dawn phenomenon) requiring more insulin 1
  • Multiple daytime meals (breakfast and lunch) requiring insulin coverage 1
  • Physical activity and stress hormones during the day increasing insulin needs 1

• Nighttime insulin requirements are lower due to:

  • Reduced food intake during sleep 1
  • Lower metabolic rate during rest 1
  • Increased risk of nocturnal hypoglycemia with higher evening doses 1

Clinical Evidence Supporting This Distribution

• Guidelines consistently recommend the 2/3 morning and 1/3 evening distribution for biphasic insulin regimens 1
• When converting from a single bedtime NPH dose to a twice-daily regimen, guidelines recommend using 80% of the total daily dose, with 2/3 given before breakfast and 1/3 given before dinner 1
• Studies show that higher morning:evening dose ratios (55:45 to 60:40) provide better glycemic control than equal distribution (50:50) in patients with type 2 diabetes 2

Special Considerations

• For steroid-induced hyperglycemia, this distribution may need adjustment, as afternoon and evening hyperglycemia are common with glucocorticoid use 1
• During Ramadan fasting or other situations with altered meal patterns, the distribution may need modification 3
• When initiating a twice-daily premixed insulin regimen, starting with this 2/3:1/3 distribution provides a foundation that can be titrated based on individual blood glucose patterns 1

Practical Implementation

• When converting from bedtime NPH to twice-daily Mixtard:

  • Calculate 80% of the current NPH dose as the new total daily dose 1
  • Give 2/3 of this new total dose before breakfast 1
  • Give 1/3 of this new total dose before dinner 1
  • Add short/rapid-acting insulin as needed based on individual requirements 1

• When adjusting doses:

  • Morning NPH component should be adjusted based on pre-lunch blood glucose 1
  • Evening NPH component should be adjusted based on fasting blood glucose 1
  • Morning rapid-acting component should be adjusted based on post-breakfast glucose 1
  • Evening rapid-acting component should be adjusted based on post-dinner glucose 1

Common Pitfalls to Avoid

• Equal distribution (50:50) may lead to suboptimal control, as studies show patients on equal distribution often require adjustment to higher morning doses over time 2
• Excessive evening doses increase the risk of nocturnal hypoglycemia 1
• Insufficient morning doses may lead to poor daytime glucose control, especially after breakfast and lunch 1, 2
• Failure to adjust the distribution based on individual glucose patterns and lifestyle factors 1