By: Allen King
When insulin first became available in 1922, the treatment goal in diabetes management was to minimize ketoacidosis and high blood glucose levels.
When the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) were published in the 1990s, it was made clear that to reduce the eye, kidney and nerve complications of diabetes, average glucose levels must be much lower. However, in these trials, the incidence of low blood glucose levels increased when lower A1C goals were attempted.
So, for the patient with diabetes, a balance is forced. The fear of high blood glucose levels and long-term complications make us try to drive the blood glucose levels down, while the dangers inherent in pushing glucose levels too low and suffering the short-term complications of hypoglycemia make us try to drive the glucose levels up.
It is clear that in order to achieve recommended glucose goals, we must give more attention to the physiological replacement of insulin. In other words, we have to learn to think like a pancreas.
Basal Bolus Physiology
In the fasting state, a small amount of insulin is needed to match the glucose that is made by the liver. This insulin is often referred to as the basal, or background, insulin.
The basal insulin level needed to keep glucose levels normal is not constant, at least in type 1 diabetes. During the evening and early morning hours, there is an increased insulin resistance, requiring higher insulin levels to maintain normal glucose levels. This so-called Dawn Phenomenon of increased insulin resistance is due to increased growth hormone or cortisol.
With meals, an increased amount of insulin is released in a two-part wave that is important to achieve ideal after-meal blood glucose levels. The first phase is the initial 10 minutes following the start of a meal. In the second phase, insulin levels slowly rise to meet the requirement of moving glucose into these tissues.
For people with diabetes, after-meal high blood glucose is dependent on the carbohydrate content of the meal. Regardless of the type of carbohydrate, the total carbohydrate load appears to be the best indicator of the after-meal glucose increase.
Therefore, proper dosing of bolus insulin requires the diabetic to match the insulin injection dose with the carbohydrates in a meal to achieve the best after-meal blood glucose control.
Basal Insulin Choices
NPH, Lente and Ultralente
For decades, insulin such as NPH, Lente and Ultralente has been available for basal insulin. These three insulins are modified into a cloudy suspension to create a prolonged action, and therefore they can be given once or twice a day.
Compared to the newer insulin analogs, the aforementioned are inexpensive. They have the disadvantage of having an unwanted peak action and a pharmacodynamic action that may vary as much as 50 percent from one injection to the next. The unwanted choice is between higher targets for glucose control or frequent meals to prevent hypoglycemia.
Lantus (insulin glargine) is an analog designed to have a desirable basal flat profile after injection, compared with the shorter duration of action and early peak of NPH insulin. Lantus is a clear insulin, unlike other long-acting insulins currently available. Compared to NPH, Lantus is associated with less weight gain and less hypoglycemia at any given level of blood glucose control. The duration of action for Lantus can range from 13 to more than 24 hours, but the average is less than 24 hours. Because of this and the need for different basal rate levels during a 24- hour period, Lantus is given twice a day for some type 1s.
Bolus Insulin Choices
Until recently, Regular insulin was the only bolus insulin. Readily available and inexpensive as compared to the newer analogs, it is not without problems when compared to the newer analog insulins. Because of the delay in onset of action, bolus insulin must be injected at least 30 minutes before eating. This delayed onset may lead to misjudging the amount needed for the meal’s carbohydrate load.
Humalog and NovoLog
Several rapid-acting insulin analogs, namely Humalog (insulin lispro), NovoLog (insulin aspart) and Apidra (insulin glulisine), are or will soon be available. There does not appear to be a clinical difference in how they perform once they are injected. Their onset is within 15 minutes after injection, with a peak at 60 minutes and a duration of four or five hours. They may be given immediately before the meal. Increased doses do not seem to prolong its action, so there is no need to project its effect into the next meal as for Regular insulin. Because of the rapid action of these analogs, they are the most commonly used insulins in pump therapy.
Initial Insulin Dosing
Resistance to adopting basal bolus therapy often seems to lie with the primary care physician. Since the provider is the one who initiates treatment, it is important that he or she believes that basal bolus dosing is the best approach.
The diabetes care team must discuss these important facts with the person with diabetes: that although one or two injections a day may be easier, that’s not how a normal pancreas acts. A normal pancreas delivers a bolus of insulin for each meal and a variable small amount all during the 24-hour period to meet the body’s basal insulin needs. The “best” treatment requires an injection before each meal and one or two basal insulin injections each day.
Once educated, both patient and provider are usually convinced of the merits of basal bolus dosing. Basal bolus dosing allows the person with diabetes to achieve a lower A1C with less likelihood of hypoglycemia. It allows for greater flexibility and eliminates the need to eat frequent meals in order to prevent hypoglycemia.