3. Methods of insulin administration

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  a. Insulin syringes and needles -  Plastic disposable syringes are available in 1-mL, 0.5-mL, and 0.3-mL sizes. The “low-dose” 0.3-mL syringes have become increasingly popular, because many diabetics do not take more than 30 units of insulin in a single injection except in rare instances of extreme insulin resistance. Two lengths of needles are available: short (8 mm) and long (12.7 mm). Long needles are preferable in obese patients to reduce variability of insulin absorption. Ultrafine needles as small as 31 gauge reduce the pain of injections. “Disposable” syringes may be reused until blunting of the needle occurs (usually after three to five injections). Sterility adequate to avoid infection with reuse appears to be maintained by recapping syringes between uses. Cleansing the needle with alcohol may not be desirable since it can dissolve the silicone coating and can increase the pain of skin puncturing.

Any part of the body covered by loose skin can be used, such as the abdomen, thighs, upper arms, flanks, and upper buttocks. Preparation with alcohol is no longer required prior to injection as long as the skin is clean. Rotation of sites continues to be recommended to avoid delayed absorption when fibrosis or lipohypertrophy occurs from repeated use of a single site. However, considerable variability of absorption rates from different sites, particularly with exercise, may contribute to the instability of glycemic control in certain type 1 patients if injection sites are rotated too frequently in different areas of the body. Consequently, it is best to limit injection sites to a single region of the body and rotate sites within that region. The abdomen is recommended for subcutaneous injections, since regular insulin has been shown to absorb more rapidly from there than from other subcutaneous sites. The effect of anatomic regions appears to be much less pronounced with the analog insulins.

  b. Insulin pen injector devices -  Insulin pens eliminate the need for carrying insulin vials and syringes. Cartridges of insulin lispro, insulin aspart, insulin glargine, regular insulin, NPH insulin, and 70% NPH/30% regular insulin are available for reusable pens (Novo Nordisk, Becton Dickinson, and Sanofi Aventis pens). Disposable prefilled pens are also available for insulin lispro, NPH, 70% NPH/30% regular, 75% NPL/25% insulin lispro, 50% NPL/50% insulin lispro, and 70% insulin aspart protamine/30% insulin aspart. Thirty-one gauge needles (5, 6, and 8 mm long) for these pens make injections almost painless.

  c. Insulin pumps -  In the United States, Medtronic Mini-Med, Animas, and Deltec Cozmo insulin infusion pumps are available for subcutaneous delivery of insulin. These pumps are small (about the size of a pager) and very easy to program. They offer many features, including the ability to set a number of different basal rates throughout the 24 hours and to adjust the time over which bolus doses are given. They also are able to detect pressure build-up if the catheter is kinked. Improvements have also been made in the infusion sets. The catheter connecting the insulin reservoir to the subcutaneous cannula can be disconnected, allowing the patient to remove the pump temporarily (eg, for bathing). The great advantage of continuous subcutaneous insulin infusion (CSII) is that it allows for establishment of a basal profile tailored to the patient. The patient therefore is able to eat with less regard to timing because the basal insulin infusion should maintain constant blood glucose between meals. Also the ability to adjust the basal insulin infusion makes it easier for the patient to manage glycemic excursions that occur with exercise.

CSII therapy is appropriate for patients who are motivated, mechanically inclined, educated about diabetes (diet, insulin action, treatment of hypoglycemia and hyperglycemia), and willing to monitor their blood glucose four to six times a day. Known complications of CSII include ketoacidosis, which can occur when insulin delivery is interrupted, and skin infections. Another disadvantage is its cost and the time demanded of physicians and staff in initiating therapy.

  d. Inhaled insulin -  A novel method for delivering a preprandial powdered form of insulin by inhalation (Exubera) has been approved by the FDA. In the clinical trials that led to the approval of this preparation, approximately 2500 adult patients with type 1 and type 2 diabetes were studied. The inhaled insulin was as effective as subcutaneous regular insulin in controlling postprandial glucose excursions, but the studies did not compare inhaled insulin with the short-acting insulin analogs.

Pharmacokinetic studies of the inhaled preparation show that it is rapidly absorbed and its onset of action is 32 minutes, compared with 48 and 41 minutes for regular insulin and insulin lispro, respectively. However, the metabolic effect is slower, and the duration of action is longer than insulin lispro and comparable to regular insulin. The bioavailability of inhaled insulin is about 10%, and so patients would need to inhale about 300-400 units of insulin a day. Inhaled insulin is administered 10 minutes prior to meals using a combination of 1- and 3-mg unit doses; 1 mg of inhaled insulin is equivalent to 3 units subcutaneous insulin injection.

Because consecutive inhalation of three 1-mg blisters is associated with a 30-40% greater insulin exposure than one 3-mg dose blister, the two regimens are not interchangeable. A small decrease in pulmonary function (forced expiratory volume in 1 second [FEV1] and single-breath diffusing capacity for carbon monoxide [DLCO]) was seen in the first few months of use, but in the phase 3 studies lasting 2 years, patients did not experience clinically significant effects on pulmonary function. The clinical trials excluded patients with pulmonary disorders. Inhaled insulin does result in higher insulin antibody titers than subcutaneous insulin, but the studies so far have not shown any clinical impact on dosage or control. Other side effects associated with Exubera therapy include cough, shortness of breath, sore throat, and dry mouth. Smokers have higher insulin levels than nonsmokers, so this insulin preparation is contraindicated in patients who smoke or who have discontinued smoking for less than 6 months. The FDA has recommended pulmonary function tests at baseline, after 6 months of treatment and every year thereafter, even if there are no pulmonary symptoms.