Use of Flexible Insulin Regimens

The management of type 1 diabetes mellitus (formerly known as insulin-dependent diabetes) has changed dramatically over the past 30 years. In particular, new insulin strategies have improved the ability to maintain near-normal glycemia. Factors such as onset, peak and duration of action can influence the ability of a particular insulin regimen to help control glucose levels. Patient factors, including individual variations in insulin absorption, levels of exercise and types of meals consumed, also influence the effectiveness of an insulin regimen. Rapid-acting insulin lispro is an ideal mealtime insulin. The premeal dose of insulin lispro can be adjusted based on the content of the meal and the patient’s blood glucose level. Intermediate-acting and long-acting insulins should not be given to account for the content of a specific meal. Long-acting insulin can be administered once daily at bedtime or, ideally, twice daily in addition to another type of insulin. Patients with type 1 diabetes typically require an insulin dosage of 0.5 to 1.0 unit per kg per day. Newly diagnosed patients may have lower initial requirements because of continued endogenous insulin production. Flexible insulin regimens are based on predetermined actions in response to self-monitoring of blood glucose levels and carbohydrate intake.

Over the past 30 years, dramatic changes have occurred in the management of type 1 diabetes mellitus (formerly known as insulin-dependent diabetes).13 Insulin replacement strategies now stress the importance of administering smaller doses of insulin throughout the day. This approach allows insulin doses to be changed as needed to correct hyperglycemia, supplement for additional anticipated carbohydrate intake or subtract for exercise.

Although significant effort is required, it has become theoretically possible to maintain near-normal glycemia in most patients with type 1 diabetes. The 1993 report from the Diabetes Control and Complications Trial (DCCT) demonstrated that meticulous glycemic control is possible and reduces the occurrence of microvascular complications in patients who have type 1 diabetes.4

Pharmacology of Insulin

Several important factors affect the absorption of subcutaneously administered insulin and explain much of the unstable glycemia that occurs in patients with type 1 diabetes. The time it takes to absorb one half of an injected dose of insulin may vary by 25 to 50 percent among individual patients.5 For example, NPH insulin may have a duration of activity of 18 hours in one patient but an effective activity of only 9 or 10 hours in another patient.

Another important factor that influences glycemia is the length of time between the administration of regular insulin or insulin lispro and the consumption of a meal (often called the “lag time”).2 This factor is perhaps the most underemphasized aspect of flexible diabetes therapy programs. In general, to ensure insulin availability during food consumption, regular insulin needs to be given 20 to 30 minutes before food consumption.6 Lag times need to be decreased when quicker-acting insulin lispro is used.

Although it is difficult to give exact recommendations on ideal lag times for the mealtime insulins (regular insulin and fast-acting insulin lispro), it is important to try to keep the timing of administration as consistent as possible. The lag time can be altered, depending on the level of premeal glycemia. Thus, when the blood glucose level is above the target range, it may be desirable to increase the lag time. Alternatively, the lag time should be decreased when premeal glycemia is below the target level, and insulin should be administered just before eating for premeal hypoglycemia.


The first insulin used, regular insulin is generally considered a mealtime insulin. However, with a peak effect in two to four hours after injection and a duration of action ranging from six to eight hours, regular insulin should also be considered a basal insulin because it still has significant activity after food is absorbed.


Insulin lispro is a fast-acting insulin analogue with a low capacity for self-aggregation in subcutaneous tissue. Regular human insulin has been shown to be equipotent to insulin lispro in terms of its binding to the insulin receptor and its effect on cellular glucose uptake.7

Although regular insulin has traditionally been classified as a short-acting insulin, insulin lispro is the first truly rapid-acting insulin. The quick action of insulin lispro makes it the ideal insulin for maintaining blood glucose levels below 180 mg per dL (10 mmol per L) for two hours after a meal, particularly when the meal contains foods that are relatively high in carbohydrates and low in fat.

When a low-carbohydrate, high-fat meal is to be eaten, the dose of insulin lispro should be adjusted downward to prevent hypoglycemia after a meal. Alternatively, when a high-fat meal is to be consumed, regular insulin may be substituted at that meal or a combination of regular insulin and insulin lispro may be used. Combined insulins, termed insulin “cocktails,” have become quite popular9 and have been shown to be useful in minimizing hyperglycemia after meals.

To date, the greatest advantage documented for insulin lispro is the reduction of hypoglycemia as a result of the better matching of insulin and food absorption.

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