POSITION STATEMENT

Insulin Administration

AMERICAN ASSOCIATION ‘

nsulin is necessary for normal carbohy- available, and other analogs are in devel- control and should only be done drate, protein, and fat metabolism. opment. Regular is a short-acting . under the supervision of a health profes- I People with mellitus do Intermediate-acting include lente sional with expertise in diabetes. Human not produce enough of this hormone to and NPH. Ultralente and insulin manufactured using recombinant sustain life and therefore depend on ex- are long-acting insulins. Insulin prepara- DNA technology is replacing insulin iso- ogenous insulin for survival. In contrast, tions with a predetermined proportion of lated from pigs. Future availability of an- individuals with are not intermediate-acting insulin mixed with imal insulin is uncertain. dependent on exogenous insulin for sur- short- or rapid-acting insulin (e.g., 70% Pharmacists and health care provid- vival. However, over time, many of these NPH/30% regular, 50% NPH/50% regu- ers should not interchange insulin species individuals will show decreased insulin lar, and 75% NPL/25% ) are or types without the approval of the pre- production, therefore requiring supple- available. scribing physician and without informing mental insulin for adequate blood glucose Different companies have adopted the patient of the type of insulin change control, especially during times of stress different names for the same short-, inter- being made. If an individual is admitted or illness. mediate-, or long-acting types of insulin to a hospital, the type of insulin he or she An insulin regimen is often required or their mixture. Human insulins have a has been using should not be changed in- in the treatment of more rapid onset and shorter duration of advertently. If there is doubt about the and diabetes associated with certain con- activity than pork insulins. principal species, human insulin should ditions or syndromes (e.g., pancreatic dis- Insulin is commercially available in be administered until adequate informa- eases, drug- or chemical-induced diabetes, concentrations of 100 or 500 units/ml tion is available. When purchasing insu- endocrinopathies, insulin-receptor disor- (designated U-100 and U-500, respec- lin, the patient should make sure that the ders, certain genetic syndromes). In all in- tively; 1 unit equals ϳ36 ␮g of insulin). type and species are correct and that the stances of insulin use, the insulin dosage U-500 is only used in rare cases of insulin insulin will be used before the expiration must be individualized and balanced with resistance when the patient requires ex- date. medical nutrition therapy and exercise. tremely large doses. U-500, insulin lispro, This position statement addresses is- , insulin glargine and 75% Storage sues regarding the use of conventional in- NPL/25% insulin lispro require a pre- sulin administration (i.e., via syringe or Vials of insulin not in use should be re- scription. Insulin preparations are some- pen with needle and cartridge) in the self- frigerated. Extreme temperatures (Ͻ36 or times formulated individually for use in care of the individual with diabetes. It Ͼ86°F, Ͻ2orϾ30°C) and excess agita- infants (e.g., U-10) with diluents pro- does not address the use of insulin pumps. tion should be avoided to prevent loss of vided by the manufacturer. In these in- (See the American Diabetes Association’s potency, clumping, frosting, or precipita- stances, special care must be taken to position statement “Continuous Subcuta- tion. Specific storage guidelines provided ensure that the correct dose of the diluted neous Insulin Infusion” for further dis- by the manufacturer should be followed. cussion on this subject.) insulin is administered with an ordinary Insulin in use may be kept at room tem- insulin syringe. perature to limit local irritation at the in- Different types and species of insulin jection site, which may occur when cold INSULIN — Insulin is obtained from have different pharmacological proper- insulin is used. pork or is made chemically ties. Human insulin is preferred for use in The patient should always have avail- identical to human insulin by recombi- pregnant women, women considering able a spare bottle of each type of insulin nant DNA technology or chemical modi- , individuals with or used. Although an expiration date is fication of pork insulin. Insulin analogs immune resistance to animal-derived in- stamped on each vial of insulin, a loss in have been developed by modifying the sulins, those initiating insulin therapy, potency may occur after the bottle has sequence of the insulin mole- and those expected to use insulin only been in use for Ͼ1 month, especially if it cule. intermittently. Insulin type and species, was stored at room temperature. Insulin is available in rapid-, short-, injection technique, insulin antibodies, The person administering insulin intermediate-, and long-acting types that site of injection, and individual patient re- should inspect the bottle before each use may be injected separately or mixed in the sponse differences can all affect the onset, for changes (i.e., clumping, frosting, pre- same syringe. Rapid-acting insulin ana- degree, and duration of insulin activity. cipitation, or change in clarity or color) logs (insulin lispro and insulin aspart) are Changing insulin species may affect blood that may signify a loss in potency. Visual ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● examination should reveal rapid- and Originally approved 1989. Most recent review/revision, 2001. short-acting insulins as well as insulin Abbreviations: SMBG, self-monitoring of blood glucose. glargine to be clear and all other insulin

S112 DIABETES CARE, VOLUME 25, SUPPLEMENT 1, JANUARY 2002 Position Statement types to be uniformly cloudy. The person lins is not recommended except for pa- vice, which retains the clipped needle in with diabetes should always try to relate tients already adequately controlled on an inaccessible compartment. In areas with ϩ any unexplained increase in blood glu- such a mixture. Upon mixing, Zn2 container-recycling programs, placement cose to possible reductions in insulin po- present in lente insulins (e.g., lente and of containers of used syringes, needles, tency. If uncertain about the potency of a ultralente) will bind with the short- and lancets with materials to be recycled vial of insulin, the individual should re- acting insulin and delay its onset of ac- is prohibited. Local trash disposal author- place the vial in question with another of tion. The degree and rate of binding ities should be consulted to determine the the same type. varies with the ratio and species of the appropriate disposition of such contain- two insulins; binding equilibrium may ers. The likelihood of reuse of a syringe by Mixing insulin not be reached for 24 h. If short-acting another person is decreased if the plunger Administration of mixtures of rapid- or and lente mixtures are to be used, the is separated from the barrel at the time of short- and intermediate- or long-acting patient should standardize the interval disposal. Disposable insulin pens that insulins will produce a more normal gly- between mixing and injection. contain a limited capacity (e.g., 150 or cemia in some patients than use of a single ● Phosphate-buffered insulins (e.g., NPH 300 units) of insulin are available. Users insulin. The formulations and particle size insulin) should not be mixed with lente select the dose, inject the insulin, and distributions of insulin products vary. On insulins. phosphate may precipi- then discard the needle according to local mixing, physicochemical changes in the tate, and the longer-acting insulin will regulations. After all of the insulin has mixture may occur (either immediately or convert to a short-acting insulin to an been used, the pen device can be dis- over time). As a result, the physiological unpredictable extent. carded in the garbage can with regular response to the insulin mixture may differ ● Insulin formulations may change; trash. from that of the injection of the insulins therefore, the manufacturer should be separately. Therefore, mixing of insulins consulted in cases where its recommen- Needle reuse should follow these guidelines: dations appear to conflict with the Manufacturers of disposable syringes and American Diabetes Association guide- pen needles recommend that they only be ● Patients who are well controlled on a lines. used once. One potential issue, which particular mixed-insulin regimen arises with reuse of syringes or needles, is should maintain their standard proce- SYRINGES — Conventional insulin the inability to guarantee sterility. Most dure for preparing their insulin doses. administration involves subcutaneous in- insulin preparations have bacteriostatic ● No other medication or diluent should jection with syringes marked in insulin additives that inhibit growth of bacteria be mixed with any insulin product un- units. There may be differences in the way commonly found on the skin. Neverthe- less approved by the prescribing physi- units are indicated, depending on the size less, syringe/needle reuse may carry an cian. of the syringe and the manufacturer. In- increased risk of infection for some indi- ● Insulin glargine should not be mixed sulin syringes are manufactured with viduals. Patients with poor personal hy- with other forms of insulin due to the 0.3-, 0.5-, 1-, and 2-ml capacities. Several giene, an acute concurrent illness, open low pH of its diluent. lengths of needles are available. Blood wounds on the hands, or decreased resis- ● Use of commercially available pre- glucose should be monitored when tance to infection for any reason should mixed insulins may be used if the insu- changing from one length to another to not reuse a syringe or pen needle. lin ratio is appropriate to the patient’s assess for variability of insulin absorption. Another issue has arisen with the ad- insulin requirements. Regulations governing the purchase of sy- vent of newer, smaller (30 and 31 gauge) ● Currently available NPH and short- ringes vary greatly from one state to an- needles. Even with one injection, the nee- acting insulin formulations when other. dle tip can become bent to form a hook mixed may be used immediately or Syringes must never be shared with which can lacerate tissue or break off to stored for future use. another person because of the risk of ac- leave needle fragments within the skin. ● When rapid-acting and ultralente insu- quiring a blood-borne viral infection The medical consequences of these find- lins are mixed, there is no blunting of (e.g., acquired immune deficiency syn- ings are unknown but may increase lipo- the onset of action of the rapid-acting drome or hepatitis). dystrophy or have other adverse effects. insulin. A slight decrease in the absorp- Travelers should be aware that insulin Some patients find it practical to re- tion rate, but not the total bioavailabil- is available in a strength of U-40 outside use needles. Certainly, a needle should be ity, is seen when rapid-acting and of the U.S. To avoid dosing errors, sy- discarded if it is noticeably dull or de- -stabilized insulin (NPH) are ringes that match the concentration of formed or if it has come into contact with mixed. In clinical trials, however, the U-40 insulin must be used. any surface other than skin. If needle re- postprandial blood glucose response use is planned, the needle must be re- was similar when rapid-acting insulin Disposal capped after each use. Patients reusing was mixed with either NPH or ultra- Regulations in some states require the de- needles should inspect injection sites for lente. When rapid-acting insulin is struction of used insulin syringes and redness or swelling and should consult mixed with either an intermediate- or needles. Recapping, bending, or breaking their healthcare provider before initiating long-acting insulin, the mixture should a needle increases the risk of needle-stick the practice and if signs of skin inflamma- be injected within 15 min before a injury. Unless the syringe will be reused, tion are detected. meal. it should be placed in a puncture-resistant Before syringe reuse is considered, it ● Mixing of short-acting and lente insu- disposal container or needle-clipping de- should be determined that the patient is

DIABETES CARE, VOLUME 25, SUPPLEMENT 1, JANUARY 2002 S113 Position Statement capable of safely recapping a syringe. isopropyl alcohol. For all insulin prepara- when this occurs. If the patient suspects Proper recapping requires adequate vi- tions, except rapid- and short-acting in- that a significant portion of the insulin sion, manual dexterity, and no obvious sulin and insulin glargine, the vial or pen dose was not administered, blood glucose tremor. The patient should be instructed should be gently rolled in the palms of the should be checked within a few hours of in a recapping technique that supports hands (not shaken) to resuspend the in- the injection. If bruising, soreness, welts, the syringe in the hand and replaces the sulin. An amount of air equal to the dose redness, or pain occur at the injection site, cap with a straight motion of the thumb of insulin required should first be drawn the patient’s injection technique should and forefinger. The technique of guiding up and injected into the vial to avoid cre- be reviewed by a physician or diabetes both the needle and cap to meet in midair ating a vacuum. For a mixed dose, putting educator. Painful injections may be min- should be discouraged, because this fre- sufficient air into both bottles before imized by the following: quently results in needle-stick injury. drawing up the dose is important. When The syringe being reused may be mixing rapid- or short-acting insulin with ● Injecting insulin at room temperature. stored at room temperature. The potential intermediate- or long-acting insulin, the ● Making sure no air bubbles remain in benefits or risks, if any, of refrigerating the clear rapid- or short-acting insulin should the syringe before injection. syringe in use or of using alcohol to be drawn into the syringe first. ● Waiting until topical alcohol (if used) cleanse the needle of a syringe are un- After the insulin is drawn into the sy- has evaporated completely before injec- known. Cleansing the needle with alcohol ringe, the fluid should be inspected for air tion. may not be desirable, because it may re- bubbles. One or two quick flicks of the ● Keeping muscles in the injection area move the silicon coating that makes for forefinger against the upright syringe relaxed, not tense, when injecting. less painful skin puncture. should allow the bubbles to escape. Air ● Penetrating the skin quickly. bubbles themselves are not dangerous but ● Not changing direction of the needle SYRINGE ALTERNATIVES — In- can cause the injected dose to be de- during insertion or withdrawal. sulin can be given with jet injectors that creased. ● Not reusing needles. inject insulin as a fine stream into the skin. These injectors offer an advantage Injection procedures Some individuals may benefit from the for patients unable to use syringes or Injections are made into the subcutane- use of prefilled syringes (e.g., the visually those with needle phobias. A potential ad- ous tissue. Most individuals are able to impaired, those dependent on others for vantage may be a more rapid absorption lightly grasp a fold of skin and inject at a drawing their insulin, or those traveling of short-acting insulin. However, the ini- 90° angle. Thin individuals or children or eating in restaurants). Prefilled syringes tial cost of these injectors is relatively can use short needles or may need to are stable for up to 30 days when kept in high, and they may traumatize the skin. pinch the skin and inject at a 45° angle to a refrigerator. If possible, the syringes They should not be viewed as a routine avoid intramuscular injection, especially should be stored in a vertical position, option for use in patients with diabetes. in the thigh area. Routine aspiration with the needle pointing upward, so that Several pen-like devices and insulin- (drawing back on the injected syringe to suspended insulin particles do not clog containing cartridges are available that check for blood) is not necessary. Partic- the needle. The predrawn syringe should deliver insulin subcutaneously through a ularly with the use of insulin pens, the be rolled between the hands before ad- needle. In many patients (e.g., especially needle should be embedded within the ministration. A quantity of syringes may those who are neurologically impaired skin for 5 s after complete depression of be premixed and stored. The effect of pre- and those using multiple daily injection the plunger to ensure complete delivery mixing of insulins on glycemic control regimens), these devices have been dem- of the insulin dose. should be assessed by a physician, based onstrated to improve accuracy of insulin Patients should be aware that air bub- on blood glucose results obtained by the administration and/or adherence. bles in an insulin pen can reduce the rate patient. When premixing is required, Low-dose pens that can deliver insu- of insulin flow from the pen; underdeliv- consistency of technique and careful lin in half-unit increments are also avail- ery of insulin can occur when air bubbles blood glucose monitoring are especially able. are present, even if the needle remains important. Insulin delivery aids (e.g., nonvisual under the skin for as long as 10 s after insulin measurement devices, syringe depressing the plunger. Air can enter the Injection site magnifiers, needle guides, and vial stabi- insulin pen reservoir during either man- Insulin may be injected into the subcuta- lizers) are available for people with visual ufacture or filling if the needle is left on neous tissue of the upper arm and the an- impairments. Information about these the pen between injections. To prevent terior and lateral aspects of the thigh, products is available in the American Di- this potential problem, avoid leaving a buttocks, and abdomen (with the excep- abetes Association’s annual diabetes re- needle on a pen between injections and tion of a circle with a 2-inch radius source guide. prime the needle with 2 units of insulin around the navel). Intramuscular injec- before injection. tion is not recommended for routine in- INJECTION TECHNIQUE If an injection seems especially pain- jections. Rotation of the injection site is ful or if blood or clear fluid is seen after important to prevent lipohypertrophy or Dose preparation withdrawing the needle, the patient lipoatrophy. Rotating within one area is Before each injection, the hands and the should apply pressure for 5–8 s without recommended (e.g., rotating injections injection site should be clean. The top of rubbing. Blood glucose monitoring systematically within the abdomen) the insulin vial should be wiped with 70% should be done more frequently on a day rather than rotating to a different area

S114 DIABETES CARE, VOLUME 25, SUPPLEMENT 1, JANUARY 2002 Position Statement with each injection. This practice may de- treatment goals should be developed with need assistance in handling illness or crease variability in absorption from day the cooperation of the patient. The timing stress. to day. Site selection should take into con- of the injection depends on blood glucose sideration the variable absorption be- levels, food consumption, exercise, and tween sites. The abdomen has the fastest types of insulin used. Variables in insulin Excess insulin is a common cause of hy- rate of absorption, followed by the arms, action (e.g., onset, peak, and duration) poglycemia. Hypoglycemia may also re- thighs, and buttocks. Exercise increases must be considered. sult from a delayed or missed meal, the rate of absorption from injection sites, Rapid-acting insulin analogs should decreased carbohydrate content of a meal, probably by increasing blood flow to the be injected within 15 min before a meal or increased physical activity, or increased skin and perhaps also by local actions. immediately after a meal. The most com- insulin absorption rates (e.g., as a result of Areas of lipohypertrophy usually show monly recommended interval between increased skin temperature due to sun- slower absorption. The rate of absorption injection of short-acting (regular) insulin bathing or exposure to hot water). All in- also differs between subcutaneous and in- and a meal is 30 min. Eating within a few sulin-requiring individuals should be tramuscular sites. The latter is faster and, minutes after (or before) injecting short- instructed to carry at least 15 g carbohy- although not recommended for routine acting insulin is discouraged because it drate to be eaten or taken in liquid form in use, can be given under other circum- substantially reduces the ability of that in- the event of a hypoglycemic reaction. stances (e.g., or de- sulin to prevent a rapid rise in blood glu- Family members, roommates, school per- hydration). cose and may increase the risk of delayed sonnel, and coworkers should be in- hypoglycemia. Guidelines should be set structed in the use of for Other considerations by the physician for the suggested interval situations when the individual cannot be Whenever possible, insulin should be between insulin injection and mealtime given carbohydrate orally. All insulin us- self-administered by the patient. In the based on factors such as blood glucose ers should carry medical identification case of children, the proper age for initi- levels, site of injection, and anticipated (e.g., a bracelet or wallet card) that alerts ating this depends on the individual de- activity during the interval. others to the fact that the wearer uses in- velopmental level of the child as well as sulin. family and social circumstances. It should not be delayed beyond adolescence. In Self-monitoring the case of the visually impaired, mechan- Whenever possible, insulin-using pa- SUMMARY — The injection of insu- ical aids are available to ensure accuracy. tients should practice self-monitoring of lin is essential for management of patients Where this is insufficient, the syringes blood glucose (SMBG). Insulin dosage ad- with type 1 diabetes and may be needed may be prefilled periodically by a relative, justments should be based on blood glu- by patients with type 2 diabetes for inter- friend, home health aide, or visiting nurse cose measurements. SMBG is extremely mittent or continuous glycemic control. and the dose may be self-injected. The valuable in patients who take insulin be- The species and dosage of insulin used latter strategy can also be applied to some cause they experience day-to-day vari- should be consistent, and the patient’s in- individuals with borderline dexterity or ability in blood glucose levels. This jection technique should be reviewed pe- arithmetical skills. For patients who are variability is influenced by differences in riodically with the diabetes care team. The completely independent in insulin ad- insulin absorption rates, insulin sensitiv- effective use of insulin to obtain the best ministration, it is still advisable to have a ity, exercise, stress, rates of food absorp- metabolic control requires an under- family member knowledgeable in the tion, and hormonal changes (e.g., standing of the duration of action of the technique in case of emergency. puberty, the menstrual cycle, menopause, various types of insulin and the relation- and pregnancy). Illness, traveling, and ship of blood glucose levels to exercise, PATIENT MANAGEMENT any change in routine (e.g., increased ex- food intake, intercurrent illness, certain ercise and a different diet during vaca- medications, and stress; SMBG; and Dosing tion) may require more frequent SMBG learning to adjust insulin dosage to The appropriate insulin dosage is depen- under the guidance of a physician. Travel achieve the individualized target goals es- dent on the glycemic response of the in- through three or more time zones re- tablished between the patient, family, and dividual to food intake and exercise quires special advice regarding insulin diabetes care team. regimens. For virtually all type 1 diabetic administration. During illness, it is im- patients and many type 2 diabetic pa- portant that insulin be continued even if tients, the time course of insulin action the patient is unable to eat or is vomiting. Bibliography requires three or more injections per day When accompanied by hyperglycemia, a American Diabetes Association: Continuous subcutaneous insulin infusion (Position to meet glycemic goals. Type 1 diabetic positive urine or blood test for ketones Statement). Diabetes Care 25 (Suppl. 1): patients and some type 2 diabetic patients during illness indicates a need for extra, S116, 2002 may also require both rapid- or short- and not less, insulin. Health professionals American Diabetes Association: Resource longer-acting insulins. A dosage algo- should obtain information regarding guide 2001. Diabetes Forecast (January):33– rithm suited to the individual’s needs and blood glucose values whenever patients 110, 2001

DIABETES CARE, VOLUME 25, SUPPLEMENT 1, JANUARY 2002 S115