Certifications

PATHOPHYSIOLOGY

Different Types of Diabetes

Landmark Studies

ADMINISTRATION DEVICES

Syringes

Long or Short?

Needle Disposal

Needle Reuse

Insulin Pens
Pen Needle Reuse

Jet Injectors

Insulin Pumps
Implantable Insulin Pumps

Inhaled Insulin

Aids for the Visually Impaired

CONCLUSIONS

REFERENCES

TABLES

Table 1 

Table 2 

Table 3 

Table 4 

Table 5 

Table 6 

Table 7 

Table 8 

Table 9 

Figure 1 

Insulin Delivery Options in 2000

Rose Marie Caffrey, MS, RN, CDE and Theresa Flaherty, BS, RN

Ms. Caffrey is a diabetes education consultant for BD Consumer Healthcare. Ms. Flaherty is Pharmacy Program Coordinator for BD Consumer Healthcare.

Introduction 

Diabetes is recognized as one of the leading causes of death and disability in the United States. Long-term complications affect virtually every part of the body, resulting in blindness, heart disease, stroke, kidney failure, nerve damage, and amputations. Uncontrolled diabetes can complicate pregnancy, and birth defects are more common in babies born to women with diabetes. 

Approximately 16 million people in the United States have diabetes, with 798,000 new cases each year. Tragically, a diagnosis is made for only half of these patients. Although diabetes occurs most often in adults, it is one of the most common chronic disorders of children in the United States. About 123,000 children and teenagers aged 19 and younger have diabetes. Diabetes is the leading cause of blindness in adults over the age of 30 and the most common cause of end-stage renal disease. Cardiovascular disease is two to four times more common in people with diabetes. Hypertension affects 60% to 65% of all people with diabetes, and strokes are two to six times more common with this chronic condition.¹ Given the prevalence of this disease, pharmacists are likely to encounter many patients with diabetes. Effective interventions by the pharmacist will assist patients in learning the appropriate skills needed to manage diabetes successfully. The purpose of this article is to provide pharmacists with information on the latest trends in insulin delivery devices, needle reuse, and aids for the visually impaired. Teaching tips are included to assist the pharmacist in integrating current trends into practice.

Pathophysiology

Diabetes is a disorder characterized by abnormalities in the metabolism of carbohydrates, proteins, and lipids as a consequence of deficiency in the synthesis, secretion, or function of insulin. Using the analogy of the body as a complicated piece of machinery, carbohydrate metabolism provides the fuel for the body’s engine to run and do work. Digestive enzymes break down ingested food into glucose, the body’s main source of fuel. After digestion, glucose is transported through the bloodstream to millions of body cells that use the nutrient for synthesis and repair. Insulin, a hormone produced by the pancreas, must be present for glucose to enter the cell. In people with diabetes, the pancreas either produces little or no insulin, the cells do not respond to the insulin that is produced, or both. As a result, blood glucose levels become characteristically elevated, while cells are deprived of the fuel needed for normal metabolism. 

Different Types of Diabetes 

Type 1 diabetes (once known as insulin-dependent diabetes, IDDM, or juvenile diabetes) is considered to be an autoimmune disease. This type of diabetes develops most often in children and young adults, and accounts for about 8% of diagnosed cases in the United States.¹ In type 1, the immune system attacks and destroys the insulin-producing beta cells in the pancreas. Exogenous insulin is necessary for survival. Symptoms usually develop over a short period of time and include excessive thirst and urination, constant hunger, weight loss, blurred vision, and fatigue. Because virtually no insulin is produced, patients with type 1 diabetes are prone to ketosis. The severe complication of ketoacidosis can develop if insulin is not administered.

Type 2 diabetes (once known as non–insulin-dependent diabetes mellitus or NIDDM) is the most common type of diabetes—accounting for 90% to 95% of all cases. This form of the disease is characterized by a relative insulin deficiency as well as insulin resistance. 

Exogenous insulin is not required for survival but may be initiated for improved glycemic control. Treatment of type 2 diabetes may include diet, exercise, oral agents, and insulin. It usually develops in adults over the age of 40 and is most common in adults over the age of 55. An estimated 80% of people with type 2 diabetes are overweight.¹ Symptoms develop gradually and include fatigue, increased thirst and urination, constant hunger, blurred vision, and frequent infections.

Gestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance with onset during pregnancy. Approximately 4% of all pregnancies in the United States are complicated by GDM—resulting in 135,000 cases annually.² Screening for GDM is usually performed between 24 and 28 weeks of gestation. Treatment may include diet, exercise, and insulin. Although glucose regulation returns to normal after delivery in most cases, women with a history of GDM carry a high risk of developing type 2 diabetes later in life.³

Landmark Studies

The Diabetes Control and Complications Trial (DCCT), conducted by the National Institutes of Health and Digestive and Kidney Diseases, studied the relationship between long-term complications of diabetes and elevated blood glucose levels in patients with type 1 diabetes.⁴ This study compared intensive insulin therapy (an approach to diabetes management utilizing frequent insulin injections) with conventional diabetes therapy and the relationship of each to the development and progression of vascular and neurologic complications. The goal for the intensive treatment group was to achieve and maintain glycemic control as close as possible to the nondiabetic range while minimizing severe hypoglycemia. The incidence of severe hypoglycemia was approximately three times higher in the intensive therapy group than in the conventional therapy group. Patients in the intensive group followed a regimen that included three or more insulin injections per day or utilization of an insulin pump. Additionally, patients measured blood glucose levels three to five times each day and were followed up at monthly clinic visits. The conventional group followed standard care comprised of one or two insulin injections per day with only occasional blood glucose monitoring. These two cohorts of patients were studied to answer two different, but related, questions: Will intensive therapy prevent the development of diabetic retinopathy in patients with no retinopathy (primary prevention)? Will intensive therapy affect the progression of early retinopathy (secondary intervention)? The DCCT (Table 1) showed, unequivocally, that lowering blood glucose levels delayed the onset and slowed the progression of diabetic retinopathy, nephropathy, and neuropathy, and reduced the risk of macrovascular disease. 

Table 1.  Results of the Diabetes Control and Complications Trial⁴ 

The United Kingdom Prospective Diabetes Study (UKPDS) was a large prospective study of type 2 patients that followed patients on average 10 years to determine⁵:

1. Whether intensive use of pharmacologic therapy to lower blood glucose levels would result in clinical benefits (ie, reduced cardiovascular and microvascular complications).

2. Whether sulfonylurea drugs, the biguanide drug metformin, or insulin have specific advantages or disadvantages. 

In addition, patients with type 2 diabetes who were also hypertensive were randomized to “tight” or “less tight” blood pressure control to ascertain the benefits of lowering blood pressure, and to assess therapeutic advantages and disadvantages of angiotensin-converting enzyme inhibitors (captopril) or beta blockers (atenolol). Trial analysis demonstrated a relationship between HbA1c and the development of microvascular and macrovascular complications.⁶ The UKPDS results (Table 2) provide strong support that vigorous treatment of type 2 diabetes can decrease morbidity and mortality by decreasing the incidence of associated chronic complications.

Table 2.  Results of United Kingdom Prospective Diabetes Study⁵ 

Administration Devices

Since the discovery of insulin by Sir Frederick Grant Banting and Charles Best in 1921, methods of insulin administration have continued to evolve and improve. Today, there are a variety of products available for insulin delivery, giving unprecedented choices to people with diabetes. These choices include disposable syringes, insulin pens, jet injection devices, and insulin pumps. Additionally, many injection aid devices for visually and physically impaired individuals are also available.

Syringes

Disposable plastic insulin syringes have been available since the early 1960s. They are inexpensive and reliable. The syringes used for insulin injections today have sharp, thin, specially lubricated needles that provide a comfortable injection. Insulin syringes are available in 1 cc (100 units), 1/2 cc (50 units), and 3/10 cc (30 units) (Table 3). Two-cc (200 units) syringes are used in rare cases of extreme insulin resistance where patients require doses in excess of 100 units per injection. The unit scale on the barrel of the syringe generally differs with syringe size. One-cc syringes are usually marked in 2-unit increments and the 1/2-cc and 3/10-cc syringes in 1-unit increments. Some syringes have dark bold print for easier visibility. All insulin syringes in the United States are µ-100 with an orange needle shield. 

Teaching Tips

Table 3.  Insulin Syringes: Size, Gauge, and Length⁷ 

Long or Short?

Today’s manufacturers of insulin syringes realize that no two people with diabetes are alike. Manufacturers offer not only choices in syringe size, but also choices in needle length and gauge. Insulin needles are available in different gauges or thicknesses; the higher the gauge, the thinner the needle. Insulin syringe needle gauges presently available are 28 G, 29 G, and 30 G. See Table 3 for more information. 

Insulin syringe needles are available in standard 1/2 (12.7mm)- or 5/16 (8 mm)-inch lengths. Some patients prefer the shorter length needle because the shorter, finer needle is more comfortable. The smaller needle size may also make the transition to injections easier for some patients, especially children. Despite the short needle’s appeal, it may not be suitable for all people with diabetes. A recent study addressed the effect of needle length on diabetes control determined by fructosamine and blood glucose levels.⁸ Fructosamine levels correlate with blood glucose and reflect an average blood glucose level during the previous 3 weeks. The study results demonstrated that:

Teaching Tips

Needle Disposal

Needle disposal has become a growing problem in the United States because of the large number of patients administering medication with syringes in the home. The Environmental Protection Agency’s current guidelines suggest syringes, lancets, and other sharp objects be placed in a hard plastic or metal container with a screw-on or other tight-fitting lid.⁹ Patients should be encouraged to check local regulations regarding sharps disposal. In areas with no regulations, the syringe should be destroyed using a clipping device that contains the needle. Such devices retain the needle in an inaccessible compartment, protecting the patient from the detached needle. After the needle is destroyed, the syringes should be contained. Recapping a needle increases the risk of needle sticks and is not recommended. All sharps, whether the needle has been clipped or not, should be placed in a container such as a plastic bleach bottle or coffee can. When the container is full, the lid should be secured with duct tape and disposed with the household trash. The patient should not use a glass bottle, which may shatter, or a clear plastic soda bottle, which allows contents to be visible. Small home sharps disposal containers are also available. These containers hold approximately 75 to 100 syringes and can be disposed of in the trash when full (unless specifically prohibited by local regulations). Home sharps containers are leakproof and puncture-resistant and help protect trash collectors from accidental needle sticks. 

Needle Reuse

In an attempt to make insulin injections virtually painless, insulin needle manufacturers have made them thinner, shorter, sharper, and better lubricated. As needles become more comfortable, they also become more delicate. Many health care professionals believe the only safety issue related to reuse is the risk of infection from injecting with a needle that is no longer sterile. Infection rarely happens if the patient practices good hygiene. Reuse does, however, result in less comfortable injections because of the reduction of needle lubricant and needle tip damage. Needle tips become progressively dull and bent with each injection. Figure 1 shows photographs of new and reused pen needles.¹⁰ Damage to insulin syringe needles is even more dramatic since a rubber stopper must first be penetrated in addition to the skin. Health concerns associated with needle reuse are the risk of needle breakage while in the skin and development of lipodystrophy caused by repeated injections into the same site with dull needles.¹¹ The FDA advises against reuse or resterilization of disposable insulin injection needles.

Figure 1.  Photographs of Used Needles

Insulin Pens

For many patients, insulin syringes remain the preferred insulin delivery device. Insulin syringes are simple to use, accommodate all types of insulin, and are relatively inexpensive. However, there is a segment of the population for whom the insulin pen may be a better option. Insulin pens are compact, portable, and discreet. Doses are selected by turning a dial. This device appeals to those patients who value convenience, since the need to carry a syringe and insulin vial are eliminated. Others prefer the ease of dialing in a correct dose versus drawing up the dose with a syringe. Insulin pens may also be a good choice for patients with visual or dexterity problems. 

There are two types of insulin pens: reusable and prefilled. The reusable pen (Table 4) requires the user to load an insulin cartridge (Table 5) into the pen and attach a pen needle. Pen needles are available in different lengths and gauges (Table 6). The patient simply dials the recommended dose and follows standard injection procedure. Prefilled disposable pens (Table 7) only require that a needle be attached before injecting.

Table 4.  Reusable Insulin Pens⁷ 

When using either type of insulin pen, it is necessary to prime the pen before each use by dialing up 1 to 2 units according to manufacturer’s directions and checking to see if a drop of insulin appears on the needle tip. If insulin is not observed on the needle tip, the steps need to be repeated. Certain considerations concerning pen use need to be understood, since the mechanics of syringe versus pen injection differ. 

Table 5.   Insulin Cartridges

When using a syringe, the plunger physically moves insulin out. However, with pen use, the plunger exerts pressure on the insulin forcing it out. Therefore, pen users must wait 5 seconds after injecting insulin before removing the needle from the skin.¹² Expiration dates for insulin cartridges also differ from those of insulin vials. 70/30 insulin in 1.5-mL cartridges expires 7 days from the time the first needle is attached for use; 1.5-mL neutral protamine Hagedorn (NPH) cartridges expire after 10 days of use. With a 3-mL pen, 70/30 insulin expires after 10 days and NPH after 14 days. Regular insulin and Humalog in both the 3-mL and 1.5- mL sizes expire in 28 days. Expiration dates are the same for Eli Lilly and Novo Nordisk insulin products.¹³

Teaching Tips

Table 6.  Needle Gauge and Lengths⁷

Table 7.  Prefilled Insulin Pens⁷ 

Pen Needle Reuse 

Insulin pens have become a popular method of insulin delivery because of their convenience. Some pen users carry a pen with the needle attached or simply reuse the needle. Patients who reuse their pen needles risk needle breakage in the skin, tissue damage, and uncomfortable injections. An even greater health risk exists as a result of leaving a pen needle attached after use. Pen needles are double-ended; one end punctures the insulin cartridge and the other end penetrates the skin. By leaving a needle attached to a pen, an open passage is created between the insulin cartridge and the environment. This can result in insulin leaking out of or air entering into the insulin cartridge. When an insulin pen is transported from warm to cool temperatures, the insulin contracts and air enters the cartridge. Air in the cartridge causes the insulin dose to be injected more slowly, resulting in an inaccurate dose. Often, after the patient removes the needle from the skin, the pen will continue to drip insulin — indicating the entire dose has not been delivered. Up to two thirds of an intended dose may not be delivered.¹² Conversely, when the pen is taken from cool to warm temperatures, the insulin in the cartridge expands and leaks out through the open passage provided by the attached needle. The result is a change in the concentration of NPH or 70/30 insulin. Both situations can lead to changes in blood glucose control. For this reason, pen needles must be removed immediately after each injection and replaced with a sterile pen needle immediately before the next injection.

Jet Injectors

For a variety of reasons, some people with diabetes prefer needle-free injection systems for insulin delivery. Jet injection technology can deliver comfortable injections without the use of a needle. These devices rely on a high-pressure source, such as a carbon dioxide cartridge or a pressure spring, to force liquid through a very small opening at a very high rate of speed. A fine spray penetrates the skin and delivers medication to the underlying tissue. Designed for easy use, jet injectors can administer injections at all the same sites on the body as a traditional needle and syringe. Usual rotation of injection sites is still necessary. Jet injectors offer the ability to deliver single or mixed insulin doses up to a maximum of 50 units. Insulin is loaded by attaching the insulin vial to the injector via an adapter. Doses can be adjusted in 0.5- to 1.0- unit increments of µ-100 insulin. Some models have an audible click for each unit loaded, thus making it appropriate for use by the visually impaired. A range of comfort settings allows for adjustment of penetration pressure depending on insulin type and volume, injection site, and skin type. Despite the ability to adjust penetration pressure, some users find the injections painful. The size of the device is also considered a disadvantage by some. Needle disposal is not a concern for jet injector users.

Teaching Tips

Insulin Pumps

External insulin pumps provide yet another insulin delivery option for people with diabetes. Continuous subcutaneous insulin infusion debuted in the early 1960s with a device so large that widespread acceptance and use were prohibited. Insulin pumps today consist of an insulin reservoir, a small battery-operated pump, and a computer chip that controls the amount of insulin the pump delivers. All three components are housed in a case roughly the size of a beeper. Insulin pumps connect to a narrow, flexible plastic tubing that ends with a needle or soft cannula inserted just under the skin near the abdomen. These infusion sets are generally changed every 2 to 3 days. Lipohypertrophy and site infection can occur if infusion sets are left in place too long. Poor or unpredictable insulin absorption may result. The pump can be worn on a belt or in a pocket. Frequent blood glucose monitoring is essential to determine insulin dosages and to ensure that insulin is being delivered.

Insulin replacement is provided in a physiologic fashion, integrating both basal insulin secretion and prandial incremental insulin secretion. Users set the pump to deliver a steady flow or “basal” amount of regular insulin in small amounts. Most pumps today have the option for setting several basal rates. Pumps dispense “bolus” doses of regular insulin (several units at a time) at meals and at times when the patient has determined that blood glucose levels are too high. The combination of basal and bolus insulin infusion more closely mimics normal pancreatic insulin secretion. The ability to control both of these rates independently gives the pump user greater flexibility in responding to anticipated and unanticipated changes in insulin needs. In addition to the more physiologic mode of insulin delivery, the insulin itself is absorbed with greater predictability. Variable insulin absorption is responsible for up to 80% of the day-to-day fluctuation in blood glucose concentrations in persons using injection-based therapy,¹⁴ whereas the regular insulin delivered by an insulin pump shows far more predictable absorption—varying by less than 2.8% from the administered 24-hour dose.¹⁵ The effectiveness of pump therapy in helping people with diabetes achieve near-normal glycemia, as well as providing greater lifestyle flexibility, has added to this device’s growing popularity (Table 8).

Table 8.  Insulin Pump Models and Features¹⁶

Teaching Tips

Implantable Insulin Pumps

Implantable insulin pumps are currently under investigation and limited to experimental use only in the United States. In this approach, pumps programmed to deliver a continuous basal rate of insulin are surgically implanted into the left side of the abdomen. The pump is disk-shaped and weighs 6 to 8 oz. Users deliver bolus insulin doses with a remote control unit that prompts the pump to give the specified amount of insulin. Studies have shown that insulin delivered intraperitoneally is absorbed rapidly and predictably. The result is hepatic delivery of insulin, which more closely resembles normal physiology.

Inhaled Insulin

Recent progress has been made in the development of inhaled insulin as an alternative to insulin injections for people with diabetes. Two multicenter clinical trials have reported findings that reveal inhaled insulin is as effective as injected insulin in achieving overall blood glucose control.^17,18 A device similar to an asthma inhaler was used in the trials to convert powdered insulin into an aerosol that then passed directly into the participant’s lungs and bloodstream. No significant side effects or changes in pulmonary function were reported. Patients administered one to two inhalations before meals. Because the experimental system used only short-acting insulin, an injection of long-acting insulin was necessary at bedtime to control blood glucose levels during the night. Additional clinical trials are currently in progress.

Aids for the Visually Impaired

Visual impairment may be a problem for people with diabetes. Short-term fluctuations in blood glucose, as well as the long-term effects of diabetes, can contribute to significant vision disturbance and loss. Drawing up a correct dose of insulin may become a daily exercise in frustration for many. Products designed to aid with accurate dose measurement are available and generally fall into three categories: nonvisual insulin measurement, needle guides and vial stabilizers, and syringe magnifiers. Some products handle more than one task (ie, magnify syringe barrel and stabilize insulin vial) (Table 9).

Table 9.  Aids for the Visually Impaired⁷ 

Conclusion

Diabetes continues to be an expensive and complicated disease that requires constant vigilance and intervention on the part of the patient to achieve good glycemic control. Although insulin has remained an integral part of therapeutic strategies over the years, choices for insulin delivery have changed dramatically in recent times. Patients with diabetes are no longer limited to one type of insulin administration, but can choose from a variety of delivery devices that best suit their personalities and lifestyle. In addition, individuals who suffer from visual impairment can be aided by a whole host of products designed to help them manage their disease independently.

References

1. U S Department of Health and Human Services. (1998). Diabetes Statistics, NIH Publication # 96-3873.

2. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus , ADA. Diabetes Care 1999; 22 (Suppl 1):S5-S19.

3. Ryan, Edmond A., et al. (1995) Defects in Insulin Secretion and Action in Women With a History of Gestational Diabetes. Diabetes, Volume 44: 506-512.

4. The Diabetes Control Complications Trial Research Group. (1993). The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Eng J of Medicine, 329: 977-986.

5. Implications of the United Kingdom Prospective Diabetes Study, (1998), Position Statement Diabetes Care 21:2180-84. 

6. UKPDS Group (1997) Plasma lipids and lipoproteins at diagnosis of NIDDM by age and sex. Diabetes Care; 20:1683-1687.

7. American Diabetes Association Resource Guide 2000, suppl. To Diabetes Forecast.

8. Ginsberg, B. (1996). Glucose control and shorter length pen needles. New Jersey, Becton Dickinson NJ.

9. Patton, W. (1990) Your Syringe is Medical Waste, Diabetes Forecast, Oct. 27-29

10. BD, Unpublished manuscript (2000). A Look at the Reuse of Insulin Needles,
Franklin Lakes, NJ

11. BD Consumer Healthcare Works to Promote Proper Use of Needles, Chain Drug Review, March 27, 2000.

12. Ginsberg, B., Parkes, J., Sparacino, C., (1994) The Kinetics of insulin administration by insulin pens. Horm Met Res, 26: 584-587.

13. Eli Lilly and Company, Indianapolis, IN and Novo Nordisk Pharmaceuticals Inc. 

14. Binder, C., et al. (1984). Insulin pharmacokinetics . Diabetes Care. (7), 188-199.

15. Lauritizen, T., et al. (1983). Pharmacokinetics of continuous subcutaneous insulin infusion. Diabetologia ( 24), 326-329.

16. The Diabetes Mall (http://wwwdiabetesnet.com).

17. Skyler, J, MD, Treatment of Type 1 Diabetes Mellitus With Inhaled Human 
Insulin: A 3-Month, Multicenter Trial, ADA 1998 Scientific Sessions.

18. Cefalu, W.T., Treatment of Type 2 Diabetes Mellitus With Inhaled Insulin: 
A 3-Month, Multidenter Trial, ADA 1998 Scientific Sessions.

Introduction  |  References

Temple University School of Pharmacy is approved by the American Council on Pharmaceutical Education (ACPE) as a provider of continuing pharmaceutical education. Its CE programs are developed in accordance with the “Criteria for Quality and Interpretive Guidelines” of ACPE. This program is acceptable for 2.0 hours of Continuing Education Credits (0.2 CEU) through October 31, 2003. ACPE Pgm I.D.  057-999-00-068-H04.