Choosing and Using InsulinsAs there are different insulins available in different parts of the world, decisions about which insulin to choose are sometimes not based upon what is ideal but more practically what is possible. Older insulins cost less than newer analogues but tend to have more variable peak and valley effects as well as producing more hypoglycaemia and hyperglycaemia as a result. Such older animal-source or human regular and NPH insulins are associated with less flexibility and greater rigidity of food and activity timing than with newer – but more costly – analogues. In previous decades without much monitoring possibility, more rigid food and activity schedules attempted to compensate for such lack of flexibility but glycaemic control was also less optimal so there were more short and long-term complications. Show In practice and because of government, insurance and financial constraints as well as inconsistent availability of insulin in many parts of the world, patients and prescribers may have to use a variety of available or donated insulins. While not ideal, this adds more learning difficulties and more problems teaching changing balancing requirements. Hence it is necessary to be familiar with the range of insulins available on the market and adapt the patient’s doses to the medications available locally even if they may change far more than is ideal. It is also true that food availability, unfortunately, in many parts of the world is also not guaranteed and so insulin dose adjustments could be designed accordingly based upon blood glucose monitoring results and algorithms created just for such purposes. Most diabetes specialists and most guidelines acknowledge that the improved control possible with modern diabetes regimens is partly attributed to the improved insulin profile available with newer but costlier analogue insulins, using MDI regimens or pumps. It should be remembered that insulin pump therapy is not the only way to have excellent glucose control. Targeted blood glucose control as proven by the landmark DCCT studies remain the essential element of T1DM care if resources can be provided for such monitoring and insulin delivery coupled with educational, nutritional and psychosocial support for the child and adolescent. 1 Fast-Acting (Regular) InsulinsRegular insulins previously were derived from cows or pigs. Over time, they were improved upon and purified to be closer to human insulin. Regular insulins usually had to be injected about 30–60 minutes ahead of food but this was rather inconvenient and so almost always was never timed correctly. Peak effects occur about 2–4 hours after injection and duration lasts 6–8 hours. Regular insulins were somewhat more variable in their action than newer analogues, a reason for their replacement by the newer rapid-acting insulin analogues. 2 Rapid-Acting InsulinsRapid-acting analogue insulins (insulin aspart [Novorapid® or Novolog® by NovoNordisk], insulin lispro [Humalog® by Eli Lilly], insulin glulisine [Apidra® by Sanofi Aventis]) have been synthetically modified to better provide immediate postprandial coverage of glycaemia. They have faster peak effect, shorter duration and shorter tail effect. Onset of action with the rapid-acting analogues is in 15–30 minutes with peak effect at 1–2 hours and duration of effect about 3–4 hours. Usually, such rapid-acting analogue insulins are given as part of an MDI regimen with meals and snacks covered accordingly and with basal insulins such as detemir or glargine. Most commonly these are available by insulin pens but can also be given via syringe. They are, of course, also used effectively with insulin pumps for combination bolus and basal insulinisation. Rapid-acting analogues can be used with NPH or any other basal insulin regimen and can also be mixed in a syringe either in premixed ratios (least flexible style) or with NPH via syringe adjusted accordingly. For very young children, especially those who are picky eaters, irregular eaters or very slow eaters, such analogues can be given just prior to food or even just after food is completed to better allow balancing of actual food or snack intake with less guessing. Such analogues, when affordable and available, have replaced the older synthetic human regular insulins or the animal-source regular insulins because of more reproducibility and less hypoglycaemia associated with their use. 3 Intermediate-Acting InsulinPreviously, basal insulin effect was provided either by lente or NPH (Neutral Protamine Hagedorn) insulin (Insulatard® or Humulin®). Lente insulin is much less available in recent years and had a slightly longer duration of effect than NPH. NPH insulin had an onset of action about 2–4 hours after administration, variable peak effects from 3–8 hours and variable duration effects of 10–18 hours. When used as a basal insulin, lente and NPH usually needed to be given at least 2 if not 3 times a day in overlapping dosage. Many healthcare teams used them as background (basal) insulin in 3 or 4 times-a-day MDI regimens to try to minimise peak effects, minimise hypoglycaemia and optimise insulin availability coupled with faster regular or rapid-acting analogues around meals. In some circumstances, they were used only twice a day particularly when there was little blood glucose monitoring or education services available. Such dosage systems frequently were insufficient to control hyperglycaemia and have mostly been supplanted by better MDI basal insulins, as described below. 4 Long-Acting Insulins (Duration 18–24 Hours)Detemir (Levemir® by NovoNordisk) and glargine (Lantus® by Sanofi-Aventis) are the currently available longer acting insulins that have often replaced NPH or lente or ultralente insulins in most modern MDI regimens. Both detemir and glargine produce lower peaks, more reproducible peaks and have more sustained and day-to-day reproducibility than prior intermediate acting or long-acting insulin. Both detemir and glargine insulins begin to have an effect from 2–4 hours after injection, reach modest peaks around 8–12 hours after injection and tend to wane after 18–24 hours. Glargine is a bit longer lasting than detemir but in smaller doses typically used in children; both may need to be given twice a day, most usually at breakfast and again at bedtime. Overnight monitoring helps to determine exact schedule needs since dosing always must be individualised. Most children and adolescents need relatively more basal insulin at bedtime compared to morning doses because of a prominent dawn effect attributed to early morning insulin resistance. Some need just the opposite distribution. Some need only a morning long-acting insulin and none at bedtime. All such decisions should be made based upon actual blood glucose monitoring profiles and not by preformed dogmatic ideas about which is a better or worse pattern. Style and amount of food and activity, of course, influence such decisions enormously. 5 ultra-Long-Lasting InsulinsUltralente is rarely available these days but previously was used as a once-at-bedtime basal insulin to avoid extra injections and couple with meal-time bolus insulins. It had some success with frequent blood glucose monitoring despite having wide variability in its peak as well as duration effectiveness. More recently ultralente has been off most markets and replaced either by insulin pumps or by glargine or detemir basal insulin preparations. 6 Mixing Insulins in the Same SyringeIt is very common to combine intermediate-acting with either regular insulin or rapid-acting as an attempt at convenience. For instance, regular and NPH at breakfast, regular alone at supper and NPH alone at bedtime; analogue plus NPH at breakfast, analogue plus NPH at suppertime. The regular or rapid-acting insulin is always drawn into the syringe first to minimise any contamination of the faster insulin with protamine. The rapid-acting doses can be adapted/adjusted every day or every meal and snack to food intake and physical exercise. Regular or rapid-acting insulin is not recommended for mixing with either glargine or detemir insulin because of potential changes in action characteristics. 7 Fixed Ratio CombinationsFixed ratio combinations also are available on the market especially in vial as well as pen formulations. They are much more commonly used with T2DM rather than T1DM but sometimes they are used when they are the only insulins available in different parts of the world. They are much more difficult to provide food flexibility since both types of insulin change in amount when the dosage changes and this occurs in fixed proportion to their formulations. Because there are two types of insulin present from the manufacturer, both types must be adapted if dose changes: the rapid-acting peak and duration effects and the more prolonged protaminated component peak. Choosing the Best Insulin for a PatientThere is no perfect insulin preparation but good glycaemic control can be reached with any insulin, even though some protocols and regimens offer more or less flexibility even as the work required to make them successful changes with patient and family interest, quality of life choices, healthcare team options and financial considerations. The choice of insulin should be individualised and based on the patient’s needs, the desired characteristics of the insulin as well as the availability and cost of the insulin and desired treatment goals and target blood glucose levels. Adherence to treatment is a key success factor of diabetes control as is frequent blood glucose monitoring and self-analysis with an emphasis on proactive adaptation of food, activity and illness for that individual’s requirements. Most intensive insulin treatment regimens currently prefer using insulin analogues since they offer faster action profiles, less waiting between insulin and food, better postprandial glucose coverage and less chance of hypoglycaemia without any compromise in overall glucose control as measured by HbA1c results. In many developing countries such analogues remain out of reach because of financial difficulties or simple unavailability. Dangers of Insulins Bought on the Informal Market or Black Market or Obtained from Donations• Integrity of the cold chain: insulin needs to have been stored properly at 2–8°C, without having been frozen or overheated at any time after it leaves the factory and before it reaches the final consumer. Insulin bought from alternative channels may not have been stored properly and may have lower potency. •Mislabelling: different products may have similar names and packaging in different countries. •Counterfeit goods may be diluted or lose potency because of improper handling or storage. What kind of insulin is given for DKA?Regular and glulisine insulin are equally effective during the acute treatment of DKA. A transition to subcutaneous glargine and glulisine after resolution of DKA resulted in similar glycemic control but in a lower rate of hypoglycemia than with NPH and regular insulin.
Why is regular insulin used for diabetic ketoacidosis?The half-life of regular insulin is less than 10 minutes. Therefore, to avoid relapse of diabetic ketoacidosis, the first subcutaneous dose of regular insulin should be given at least one hour before intravenous insulin is discontinued. A protocol for the administration of subcutaneous insulin is included in Figure 2.
When should insulin infusion be given in DKA?Subcutaneous insulin should be started when DKA has resolved and the patient is able to tolerate oral feeding. It is important to continue IV insulin infusion for 2 h after starting the subcutaneous insulin regimen to ensure adequate blood insulin levels and to prevent the recurrence of hyperglycemia and ketoacidosis.
Can insulin be given IM in DKA?The recommended mode of treatment of DKA is bolus intravenous (IV) or intramuscular (IM) short-acting insulin followed by continuous IV infusion. The IV therapy has the advantage of rapid onset of action and maintenance of a steady level of insulin in the blood.
|
