Insulin

Insulin formulation and species

• Many formulations of insulin are available; most have some role in the management of type 1 diabetes (Table 6).
• Most children are prescribed human insulins because of their availability through modern manufacturing techniques using recombinant DNA technology and because of their low immunogenicity

Short-acting insulin

• Short-acting (soluble, regular) insulin is used as an essential component of most daily replacement regimens
  either 
  
  • in combination with intermediate-acting insulin in a twice-daily regimen
  
  or
  
  • as pre-meal bolus injections in basal-bolus regimens (20–30 min before meals)
• Soluble is the only insulin suitable for IV therapy

• Soluble insulin is used in the following crisis situations
  • diabetic ketoacidosis
  • control of diabetes during surgical procedures
  • hyperglycemic episodes at home (e.g. during intercurrent illness)

Rapid-acting insulin analogs

• Rapid-acting analogs can be given immediately before meals because there is evidence that the rapid action not only reduces postprandial hyperglycemia but that postprandial and nocturnal hypoglycemia may also be reduced. In selected children they offer the useful option of being given after food to toddlers who are reluctant to eat
• Rapid-acting analogs may also be used during sick days with hyperglycemia and potential ketosis
• Rapid-acting analogs are most often used as prandial or snack boluses in combination with longer acting insulins given twice or more times daily

All children should have soluble or rapid-acting insulin available for crisis management

Intermediate-acting insulins

• The action profiles of these insulins make them suitable for twice-daily regimens and for pre-bed dosage in basal-bolus regimens

• Isophane NPH (neutral protamine Hagedorn) insulins
• Crystalline zinc acetate insulin (insulin zinc suspensions [IZS] or lente insulins)

• When soluble insulin is mixed with lente preparations it reacts with excess zinc, blunting its short-acting properties

Long-acting insulins

• Ultralente® and Ultratard® insulins were designed to have a duration of action of more than 24 h to meet basal insulin requirements and therefore could be used in basal-bolus injection regimens. Their action profile in children appears to be extremely variable and they may have to be injected twice daily to meet basal insulin requirements
• A long-acting insulin analog has recently become available

Pre-mixed insulin preparations

• Pre-mixed insulins (fixed ratio mixtures of soluble and isophane) are popular in some countries particularly for prepubertal children on twice-daily regimens. Although they reduce potential errors in drawing up insulin, they remove the flexibility offered by separate adjustment of the two types. Such flexibility is useful for children with variable food intake
• There is no clear evidence that pre-mixed insulins in young children are less effective, but there is some evidence of poorer metabolic control when they are used in adolescents
• Pre-mixed insulins with soluble:isophane in different ratios, e.g. 10:90, 15:85, 20:80, 25:75, 30:70, 40:60 and 50:50, are available in various countries from different manufacturers
• Pre-mixed insulins are most commonly used in pen injector devices
• Pre-mixed insulins may be useful when compliance (or adherence) to the regimen is a problem