Individualizing Insulin Therapy in Type 1 Diabetes Mellitus

Type 1 diabetes mellitus is an autoimmune disorder characterized by destruction of pancreatic beta cells and resulting in absolute insulin deficiency. Approximately 10% of patients with diabetes have type 1. It has been previously referred to as juvenile- onset diabetes or insulin-dependent diabetes. It usually develops in childhood or early adulthood but may occur at any age. The onset of symptoms usually is abrupt.

Tight control of blood glucose levels, as demonstrated in the Diabetes Control and Complications Trial, has shown a reduction in the development of microvascular complications in type 1 diabetes mellitus.¹ The American Diabetes Association recommends maintaining glycosylated hemoglobin at <7% and supports a more stringent goal of <6% for individual patients.² As a result, patients are being asked to take more responsibility for self-monitoring and making dose adjustments to their insulin regimens.

Types of Insulin

The goal of insulin therapy is to mimic normal insulin secretion by the pancreas. Normal insulin secretion consists of basal and mealtime insulin secretion. Basal insulin is the background insulin that the pancreas secretes continually. Mealtime insulin is the insulin that the pancreas secretes to counteract the postprandial rise in blood glucose (Table 1).

Basal Insulin

Intermediate-and long-acting insulins mimic basal insulin secretion. These products help suppress hepatic glucose production overnight and between meals. Neutral Protamine Hagedorn (NPH) insulin is one of the most commonly used intermediateacting insulins. Both NPH and Lente insulin need to be administered twice daily to provide adequate basal coverage. Problems with the intermediateacting insulins include variable absorption with the suspensions, unwanted peaks, and inadequate duration of action. These problems can result in conditions such as nocturnal hypoglycemia and fasting hyperglycemia.

The long-acting insulins such as Ultralente insulin and to a greater extent Insulin Glargine allow for 24- hour peakless coverage with just 1 injection per day. When injected before the evening meal or at bedtime, these insulins can avoid the adverse effects of nocturnal hypoglycemia or fasting hyperglycemia caused by the intermediate-acting insulins.

Mealtime Insulin

For adequate overall control, basal insulins must be used in combination with short-acting insulins. Short-acting insulins and the rapid-acting insulin analogs mimic mealtime insulin secretion that occurs during and up to 30 minutes after a meal. Regular insulin has been used before meals to mimic this pattern. Problems have occurred, however, because the onset of action of regular insulin is not as rapid as the rise in blood glucose, and absorption after subcutaneous administration often is delayed due to the formation of hexamers. This action results in postprandial hyperglycemia and late hypoglycemia. The rapid-acting insulin analogs were synthesized to overcome these problems with regular insulin. They have a faster rate of absorption and a shorter duration of action.

Insulin Regimens

Insulin therapy in patients newly diagnosed with type 1 diabetes usually is initiated at a dose of 0.3 to 0.8 units per kilogram per day in 2 divided doses. Patients often are started with two thirds of the total daily dose given as basal insulin (NPH) and a short-acting insulin, administered before breakfast in a 2:1 ratio; and the remaining one third of the dose using the 2 insulins, administered before the evening meal in a 1:1 ratio (Figure).

Almost all patients with type 1 diabetes require more intensive insulin regimens to maintain optimal blood glucose control. Self-monitoring of blood glucose is recommended several times daily, because many factors, such as food consumption, exercise, illness, stress, and alcohol, can influence insulin requirements. The split-dose regimen in the figure is easy to follow, but it can be associated with midday and nocturnal hypoglycemia. These problems can be overcome with a midmorning snack and by switching the basal insulin from predinner to bedtime. This regimen would require 3 injections, however. Some patients use mealtime insulin before each meal and a basal insulin at bedtime. This regimen requires 4 daily injections but offers patients more flexibility to adjust the regimen in accordance with their meal and exercise schedule.

An individualized patient action plan should be developed that takes into account patient preferences, goals, types of insulin, food intake, and exercise. Patients should be instructed within this action plan on how to adjust their regimen in response to results from self-monitoring of blood glucose, when a large meal is eaten, or during illness.

Insulin Mixtures

In patients with predictable schedules and habits, premixed insulins combining NPH with regular insulin (Humulin 70/30 or 50/50, Novolin 70/30) or intermediate-acting insulin analogs with rapid-acting insulin analogs (Humalog Mix 75/25, Novolog Mix) may be used twice daily. More and more patients are mixing their own insulin preparations, however, in order to comply with more intense individualized insulin regimens. Table 2 reviews the compatibility of the available insulins.

When mealtime insulin is combined with basal insulin, mealtime insulin always should be drawn up into the syringe first. Mixtures of regular and NPH insulin are stable for 1 month at room temperature or up to 3 months in the refrigerator. These mixtures also can be stored in prefilled plastic or glass syringes for 1 week to possibly 14 days under refrigeration. Filled syringes should be kept in a vertical or oblique position with the needle pointing upward to avoid plugging problems. Mixtures of regular and lente insulin should be used either immediately or 24 hours after mixing, because the zinc in the Lwente insulin will temporarily bind to the regular insulin and then dissociate. Mixtures of insulin analogs with compatible basal insulins should be injected immediately after mixing.

Insulin Pump

The insulin pump, which delivers a continuous subcutaneous insulin infusion, is available for highly motivated patients as an alternative to multiple insulin injections to improve glycemic control. Insulin pumps are small (about the size of a deck of cards), lightweight, portable, and battery-driven. The pump uses regular insulin or rapid-acting insulin analogs and can be programmed to deliver a continuous basal amount of insulin and boluses at mealtime.

Adverse Effects

The 2 major adverse effects associated with insulin administration are hypoglycemia and weight gain. Hypoglycemia often is defined as a blood glucose level of <70 mg/dL. Causes of hypoglycemia can include too much insulin, improper timing of administration, inadequate food intake, increased exercise, and alcohol consumption. Symptoms of hypoglycemia include hunger, weakness, dizziness, mood changes, sweating, tremor, and increased heart rate or?in more severe cases (blood glucose <40 mg/dL)?confusion, unconsciousness, and seizures.

At all times, patients should carry with them glucose tablets or gel or have access to a sugary food or beverage (eg, ¹/² cup of orange juice, 4-6 sugar cubes, ¹/³ cup of raisins). Patients with type 1 diabetes also should carry a glucagon emergency kit. Family members and coworkers should be advised about proper preparation and administration techniques.

Weight gain occurs because insulin promotes fat storage and increases lean body mass. This side effect, however, tends to be of greater significance in patients with type 2 diabetes who are using insulin.

Role of the Pharmacist

Pharmacists can play a vital role in the care of patients with type 1 diabetes. Insulin therapy is complex and challenging. Pharmacists can provide patients with education about their disease state and the role of insulin therapy. Pharmacists should familiarize themselves with the devices for insulin delivery and for self-monitoring of blood glucose. Pharmacists also can work with patients and physicians to identify possible causes of failure to achieve glycemic control and how to handle adverse reactions to therapy.

Dr. Singla is an assistant professor of pharmacy practice at Midwestern University College of Pharmacy?Glendale, Glendale, Ariz.

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