P O S I T I O N
`
`S T A T E M E N T
`
`Insulin Administration
`
`AMERICAN DIABETES ASSOCIATION
`
`I nsulin is necessary for normal carbohy-
`
`drate, protein, and fat metabolism.
`People with type 1 diabetes mellitus do
`not produce enough of this hormone to
`sustain life and therefore depend on ex-
`ogenous insulin for survival. In contrast,
`individuals with type 2 diabetes are not
`dependent on exogenous insulin for sur-
`vival. However, over time, many of these
`individuals will show decreased insulin
`production, therefore requiring supple-
`mental insulin for adequate blood glucose
`control, especially during times of stress
`or illness.
`An insulin regimen is often required
`in the treatment of gestational diabetes
`and diabetes associated with certain con-
`ditions or syndromes (e.g., pancreatic dis-
`eases, drug- or chemical-induced diabetes,
`endocrinopathies, insulin-receptor disor-
`ders, certain genetic syndromes). In all in-
`stances of insulin use, the insulin dosage
`must be individualized and balanced with
`medical nutrition therapy and exercise.
`This position statement addresses is-
`sues regarding the use of conventional in-
`sulin administration (i.e., via syringe or
`pen with needle and cartridge) in the self-
`care of the individual with diabetes. It
`does not address the use of insulin pumps.
`(See the American Diabetes Association’s
`position statement “Continuous Subcuta-
`neous Insulin Infusion” for further dis-
`cussion on this subject.)
`
`Intermediate-acting insulins include lente
`and NPH. Ultralente and insulin glargine
`are long-acting insulins. Insulin prepara-
`tions with a predetermined proportion of
`intermediate-acting insulin mixed with
`short- or rapid-acting insulin (e.g., 70%
`NPH/30% regular, 50% NPH/50% regu-
`lar, and 75% NPL/25% insulin lispro) are
`available.
`Different companies have adopted
`different names for the same short-, inter-
`mediate-, or long-acting types of insulin
`or their mixture. Human insulins have a
`more rapid onset and shorter duration of
`activity than pork insulins.
`Insulin is commercially available in
`concentrations of 100 or 500 units/ml
`(designated U-100 and U-500, respec-
`tively; 1 unit equals ⬃36 ␮g of insulin).
`U-500 is only used in rare cases of insulin
`resistance when the patient requires ex-
`tremely large doses. U-500, insulin lispro,
`insulin aspart, insulin glargine, and 75%
`NPL/25% insulin lispro require a pre-
`scription. Insulin preparations are some-
`times formulated individually for use in
`infants (e.g., U-10) with diluents pro-
`vided by the manufacturer. In these in-
`stances, special care must be taken to
`ensure that the correct dose of the diluted
`insulin is administered with an ordinary
`insulin syringe.
`Different types and species of insulin
`have different pharmacological proper-
`ties. Human insulin is preferred for use in
`INSULIN — Insulin is obtained from
`pregnant women, women considering
`pork pancreas or is made chemically iden-
`pregnancy, individuals with allergies or
`tical to human insulin by recombinant
`immune resistance to animal-derived in-
`DNA technology or chemical modifica-
`sulins, those initiating insulin therapy,
`tion of pork insulin. Insulin analogs have
`and those expected to use insulin only
`been developed by modifying the amino
`intermittently. Insulin type and species,
`acid sequence of the insulin molecule.
`injection technique, insulin antibodies,
`Insulin is available in rapid-, short-,
`site of injection, and individual patient re-
`intermediate-, and long-acting types that
`sponse differences can all affect the onset,
`may be injected separately or mixed in the
`degree, and duration of insulin activity.
`same syringe. Rapid-acting insulin ana-
`Changing insulin species may affect blood
`logs (insulin lispro and insulin aspart) are
`glucose control and should only be done
`available, and other analogs are in devel-
`under the supervision of a health profes-
`opment. Regular is a short-acting insulin.
`● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●
`
`Originally approved 1989. Most recent review/revision 2002.
`Abbreviations: SMBG, self-monitoring of blood glucose.
`
`sional with expertise in diabetes. Human
`insulin manufactured using recombinant
`DNA technology is replacing insulin iso-
`lated from pigs. Future availability of an-
`imal insulin is uncertain.
`Pharmacists and health care provid-
`ers should not interchange insulin species
`or types without the approval of the pre-
`scribing physician and without informing
`the patient of the type of insulin change
`being made. If an individual is admitted
`to a hospital, the type of insulin he or she
`has been using should not be changed in-
`advertently. If there is doubt about the
`principal species, human insulin should
`be administered until adequate informa-
`tion is available. When purchasing insulin,
`the patient should make sure that the type
`and species are correct and that the insu-
`lin will be used before the expiration date.
`In the event that a patient’s specific
`brand of insulin is temporarily unavail-
`able, the same insulin formulation from
`another manufacturer may be substi-
`tuted. Changing insulin types (e.g., long,
`intermediate, short, and rapid acting)
`from one formulation to another should
`always be done under medical supervi-
`sion. The patient should be fully informed
`as to the reason for any change in insulin
`and the potential need for additional glu-
`cose monitoring.
`
`Storage
`Vials of insulin not in use should be re-
`frigerated. Extreme temperatures (⬍36 or
`⬎86°F, ⬍2 or⬎30°C) and excess agita-
`tion should be avoided to prevent loss of
`potency, clumping, frosting, or precipita-
`tion. Specific storage guidelines provided
`by the manufacturer should be followed.
`Insulin in use may be kept at room tem-
`perature to limit local irritation at the in-
`jection site, which may occur when cold
`insulin is used.
`The patient should always have avail-
`able a spare bottle of each type of insulin
`used. Although an expiration date is
`stamped on each vial of insulin, a loss in
`potency may occur after the bottle has
`been in use for ⬎1 month, especially if it
`was stored at room temperature.
`
`DIABETES CARE, VOLUME 26, SUPPLEMENT 1, JANUARY 2003
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`S121
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`Page 1 of 4
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`KOIOS Exhibit 1015
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`

`
`Position Statement
`
`The person administering insulin
`should inspect the bottle before each use
`for changes (i.e., clumping, frosting, pre-
`cipitation, or change in clarity or color)
`that may signify a loss in potency. Visual
`examination should reveal rapid- and
`short-acting insulins as well as insulin
`glargine to be clear and all other insulin
`types to be uniformly cloudy. The person
`with diabetes should always try to relate
`any unexplained increase in blood glu-
`cose to possible reductions in insulin po-
`tency. If uncertain about the potency of a
`vial of insulin, the individual should re-
`place the vial in question with another of
`the same type.
`
`Mixing insulin
`Administration of mixtures of rapid- or
`short- and intermediate- or long-acting
`insulins will produce a more normal gly-
`cemia in some patients than use of a single
`insulin. The formulations and particle size
`distributions of insulin products vary. On
`mixing, physicochemical changes in the
`mixture may occur (either immediately or
`over time). As a result, the physiological
`response to the insulin mixture may differ
`from that of the injection of the insulins
`separately. When rapid-acting and ultra-
`lente insulins are mixed, there is no blunt-
`ing of the onset of action of the rapid-
`acting insulin. A slight decrease in the
`absorption rate, but not the total bioavail-
`ability, is seen when rapid-acting and pro-
`tamine-stabilized insulin (NPH) are
`mixed. In clinical trials, however, the
`postprandial blood glucose response was
`similar when rapid-acting insulin was
`mixed with either NPH or ultralente. Mix-
`ing of short-acting and lente insulins is
`not recommended, except for patients al-
`ready adequately controlled on such a
`mixture. Upon mixing, Zn2⫹ present in
`lente insulins) (e.g., lente and ultralente)
`will bind with the short-acting insulin
`and delay its onset of action. The degree
`and rate of binding varies with the ratio
`and species of the two insulins; binding
`equilibrium may not be reached for 24 h.
`Phosphate-buffered insulins (e.g., NPH
`insulin) should not be mixed with lente
`insulins. Zinc phosphate may precipitate,
`and the longer-acting insulin will convert
`to a short-acting insulin to an unpredict-
`able extent. Mixing of insulins should fol-
`low these guidelines:
`
`● Patients who are well controlled on a
`particular mixed-insulin regimen should
`
`maintain their standard procedure for
`preparing their insulin doses.
`● No other medication or diluent should
`be mixed with any insulin product un-
`less approved by the prescribing physi-
`cian.
`● Insulin glargine should not be mixed
`with other forms of insulin due to the
`low pH of its diluent.
`● Use of commercially available pre-
`mixed insulins may be used if the insu-
`lin ratio is appropriate to the patient’s
`insulin requirements.
`● Currently available NPH and short-
`acting insulin formulations when
`mixed may be used immediately or
`stored for future use.
`● Rapid-acting insulin can be mixed with
`NPH, lente, and ultralente.
`● When rapid-acting insulin is mixed
`with either an intermediate- or long-
`acting insulin, the mixture should be
`injected within 15 min before a meal.
`● Mixing of short-acting and lente insu-
`lins is not recommended except for pa-
`tients already adequately controlled on
`such a mixture. If short-acting and lente
`mixtures are to be used, the patient
`should standardize the interval be-
`tween mixing and injection.
`● Phosphate-buffered insulins (e.g.,
`NPH) should not be mixed with lente
`insulins.
`● Insulin formulations may change;
`therefore, the manufacturer should be
`consulted in cases where its recommen-
`dations appear to conflict with the
`American Diabetes Association guidelines.
`
`SYRINGES — Conventional insulin
`administration involves subcutaneous in-
`jection with syringes marked in insulin
`units. There may be differences in the way
`units are indicated, depending on the size
`of the syringe and the manufacturer. In-
`sulin syringes are manufactured with
`0.3-, 0.5-, 1-, and 2-ml capacities. Several
`lengths of needles are available. Blood
`glucose should be monitored when
`changing from one length to another to
`assess for variability of insulin absorption.
`Regulations governing the purchase of sy-
`ringes vary greatly from one state to an-
`other.
`Many different medical devices have
`been developed to reduce the risk of nee-
`dle sticks and other sharps injuries using
`current OSHA standards. These devices
`incorporate features designed to reduce
`injury. Use of some currently available
`
`insulin syringes with engineered sharps
`injury protection (ESIP) may present bar-
`riers to effective insulin self-administra-
`tion training. Use of a device for training
`that is different from the device to be used
`in practice is inconsistent with teaching/
`learning principles, and may compromise
`the success of the training process. Indi-
`vidualized patient assessment should
`guide the use of an ESIP insulin syringe
`during insulin self-administration in-
`struction. (See AADE, Diabetes Educ 28:
`730, 2000).
`Syringes must never be shared with
`another person because of the risk of ac-
`quiring a blood-borne viral infection
`(e.g., acquired immune deficiency syn-
`drome or hepatitis).
`Travelers should be aware that insulin
`is available in a strength of U-40 outside
`of the U.S. To avoid dosing errors, sy-
`ringes that match the concentration of
`U-40 insulin must be used.
`Disposal
`Recapping, bending, or breaking a needle
`increases the risk of needle-stick injury
`and should be avoided. Insulin syringes
`and pens, needles, and lancets should be
`disposed of according to local regulations.
`Some areas may have special needle dis-
`posal programs to prevent sharps from
`being in the main waste disposal stream.
`When community disposal programs are
`unavailable, used sharps should be placed
`in a puncture-resistant container. Local
`trash authorities should be contacted for
`proper disposal of filled containers. Care
`should be taken to keep these filled con-
`tainers away from containers to be recy-
`cled. In areas with container-recycling
`programs, placement of containers of
`used syringes, needles, and lancets with
`materials to be recycled is prohibited.
`Needle reuse
`Manufacturers of disposable syringes and
`pen needles recommend that they only be
`used once. One potential issue, which
`arises with reuse of syringes or needles, is
`the inability to guarantee sterility. Most
`insulin preparations have bacteriostatic
`additives that inhibit growth of bacteria
`commonly found on the skin. Neverthe-
`less, syringe/needle reuse may carry an
`increased risk of infection for some indi-
`viduals. Patients with poor personal hy-
`giene, an acute concurrent illness, open
`wounds on the hands, or decreased resis-
`tance to infection for any reason should
`not reuse a syringe or pen needle.
`
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`©
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`DIABETES CARE, VOLUME 26, SUPPLEMENT 1, JANUARY 2003
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`Page 2 of 4
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`KOIOS Exhibit 1015
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`
`Another issue has arisen with the ad-
`vent of newer, smaller (30 and 31 gauge)
`needles. Even with one injection, the nee-
`dle tip can become bent to form a hook
`which can lacerate tissue or break off to
`leave needle fragments within the skin.
`The medical consequences of these find-
`ings are unknown but may increase lipo-
`dystrophy or have other adverse effects.
`Some patients find it practical to re-
`use needles. Certainly, a needle should be
`discarded if it is noticeably dull or de-
`formed or if it has come into contact with
`any surface other than skin. If needle re-
`use is planned, the needle must be re-
`capped after each use. Patients reusing
`needles should inspect injection sites for
`redness or swelling and should consult
`their healthcare provider before initiating
`the practice and if signs of skin inflamma-
`tion are detected.
`Before syringe reuse is considered, it
`should be determined that the patient is
`capable of safely recapping a syringe.
`Proper recapping requires adequate vi-
`sion, manual dexterity, and no obvious
`tremor. The patient should be instructed
`in a recapping technique that supports
`the syringe in the hand and replaces the
`cap with a straight motion of the thumb
`and forefinger. The technique of guiding
`both the needle and cap to meet in midair
`should be discouraged, because this fre-
`quently results in needle-stick injury.
`The syringe being reused may be
`stored at room temperature. The potential
`benefits or risks, if any, of refrigerating the
`syringe in use or of using alcohol to
`cleanse the needle of a syringe are un-
`known. Cleansing the needle with alcohol
`may not be desirable, because it may re-
`move the silicon coating that makes for
`less painful skin puncture.
`
`SYRINGE ALTERNATIVES — In-
`sulin can be given with jet injectors that
`inject insulin as a fine stream into the
`skin. These injectors offer an advantage
`for patients unable to use syringes or
`those with needle phobias. A potential ad-
`vantage may be a more rapid absorption
`of short-acting insulin. However, the ini-
`tial cost of these injectors is relatively
`high, and they may traumatize the skin.
`They should not be viewed as a routine
`option for use in patients with diabetes.
`Several pen-like devices and insulin-
`containing cartridges are available that
`deliver insulin subcutaneously through a
`needle. In many patients (e.g., especially
`
`those who are neurologically impaired
`and those using multiple daily injection
`regimens), these devices have been dem-
`onstrated to improve accuracy of insulin
`administration and/or adherence.
`Low-dose pens that can deliver insu-
`lin in half-unit increments are also avail-
`able.
`Insulin delivery aids (e.g., nonvisual
`insulin measurement devices, syringe
`magnifiers, needle guides, and vial stabi-
`lizers) are available for people with visual
`impairments. Information about these
`products is available in the American Di-
`abetes Association’s annual diabetes re-
`source guide.
`
`INJECTION TECHNIQUE
`Dose preparation
`Before each injection, the insulin label
`should be verified to avoid injecting an
`incorrect insulin. The hands and the in-
`jection site should be clean. For all insulin
`preparations, except rapid- and short-
`acting insulin and insulin glargine, the
`vial or pen should be gently rolled in the
`palms of the hands (or shaken gently) to
`resuspend the insulin. An amount of air
`equal to the dose of insulin required
`should first be drawn up and injected into
`the vial to avoid creating a vacuum. For a
`mixed dose, putting sufficient air into
`both bottles before drawing up the dose is
`important. When mixing rapid- or short-
`acting insulin with intermediate- or long-
`acting insulin, the clear rapid- or short-
`acting insulin should be drawn into the
`syringe first.
`After the insulin is drawn into the sy-
`ringe, the fluid should be inspected for air
`bubbles. One or two quick flicks of the
`forefinger against the upright syringe
`should allow the bubbles to escape. Air
`bubbles themselves are not dangerous but
`can cause the injected dose to be decreased.
`Injection procedures
`Injections are made into the subcutane-
`ous tissue. Most individuals are able to
`lightly grasp a fold of skin, release the
`pinch, then inject at a 90° angle. Thin in-
`dividuals or children can use short nee-
`dles or may need to pinch the skin and
`inject at a 45° angle to avoid intramuscu-
`lar injection, especially in the thigh area.
`Routine aspiration (drawing back on the
`injected syringe to check for blood) is not
`necessary. Particularly with the use of in-
`sulin pens, the needle should be embed-
`ded within the skin for 5 s after complete
`
`Insulin Administration
`
`depression of the plunger to ensure com-
`plete delivery of the insulin dose.
`Patients should be aware that air bub-
`bles in an insulin pen can reduce the rate
`of insulin flow from the pen; underdeliv-
`ery of insulin can occur when air bubbles
`are present, even if the needle remains
`under the skin for as long as 10 s after
`depressing the plunger. Air can enter the
`insulin pen reservoir during either man-
`ufacture or filling if the needle is left on
`the pen between injections. To prevent
`this potential problem, avoid leaving a
`needle on a pen between injections and
`prime the needle with 2 units of insulin
`before injection.
`If an injection seems especially pain-
`ful or if blood or clear fluid is seen after
`withdrawing the needle, the patient
`should apply pressure for 5– 8 s without
`rubbing. Blood glucose monitoring
`should be done more frequently on a day
`when this occurs. If the patient suspects
`that a significant portion of the insulin
`dose was not administered, blood glucose
`should be checked within a few hours of
`the injection. If bruising, soreness, welts,
`redness, or pain occur at the injection site,
`the patient’s injection technique should
`be reviewed by a physician or diabetes
`educator. Painful injections may be min-
`imized by the following:
`
`● Injecting insulin at room temperature.
`● Making sure no air bubbles remain in
`the syringe before injection.
`● Waiting until topical alcohol (if used)
`has evaporated completely before injec-
`tion.
`● Keeping muscles in the injection area
`relaxed, not tense, when injecting.
`● Penetrating the skin quickly.
`● Not changing direction of the needle
`during insertion or withdrawal.
`● Not reusing needles.
`
`Some individuals may benefit from the
`use of prefilled syringes (e.g., the visually
`impaired, those dependent on others for
`drawing their insulin, or those traveling
`or eating in restaurants). Prefilled syringes
`are stable for up to 30 days when kept in
`a refrigerator. If possible, the syringes
`should be stored in a vertical position,
`with the needle pointing upward, so that
`suspended insulin particles do not clog
`the needle. The predrawn syringe should
`be rolled between the hands before ad-
`ministration. A quantity of syringes may
`be premixed and stored. The effect of pre-
`mixing of insulins on glycemic control
`
`DIABETES CARE, VOLUME 26, SUPPLEMENT 1, JANUARY 2003
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`KOIOS Exhibit 1015
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`
`Position Statement
`
`should be assessed by a physician, based
`on blood glucose results obtained by the
`patient. When premixing is required,
`consistency of technique and careful
`blood glucose monitoring are especially
`important.
`Injection site
`Insulin may be injected into the subcuta-
`neous tissue of the upper arm and the an-
`terior and lateral aspects of the thigh,
`buttocks, and abdomen (with the excep-
`tion of a circle with a 2-inch radius
`around the navel). Intramuscular injec-
`tion is not recommended for routine in-
`jections. Rotation of the injection site is
`important to prevent lipohypertrophy or
`lipoatrophy. Rotating within one area is
`recommended (e.g., rotating injections
`systematically within the abdomen)
`rather than rotating to a different area
`with each injection. This practice may de-
`crease variability in absorption from day
`to day. Site selection should take into con-
`sideration the variable absorption be-
`tween sites. The abdomen has the fastest
`rate of absorption, followed by the arms,
`thighs, and buttocks. Exercise increases
`the rate of absorption from injection sites,
`probably by increasing blood flow to the
`skin and perhaps also by local actions.
`Areas of lipohypertrophy usually show
`slower absorption. The rate of absorption
`also differs between subcutaneous and in-
`tramuscular sites. The latter is faster and,
`although not recommended for routine
`use, can be given under other circum-
`stances (e.g., diabetic ketoacidosis or de-
`hydration).
`Other considerations
`Whenever possible, insulin should be
`self-administered by the patient. In the
`case of children, the proper age for initi-
`ating this depends on the individual de-
`velopmental level of the child as well as
`family and social circumstances. It should
`not be delayed beyond adolescence. In
`the case of the visually impaired, mechan-
`ical aids are available to ensure accuracy.
`Where this is insufficient, the syringes
`may be prefilled periodically by a relative,
`friend, home health aide, or visiting nurse
`and the dose may be self-injected. The
`latter strategy can also be applied to some
`individuals with borderline dexterity or
`arithmetical skills. For patients who are
`completely independent in insulin ad-
`ministration, it is still advisable to have a
`family member knowledgeable in the
`technique in case of emergency.
`
`PATIENT MANAGEMENT
`Dosing
`The appropriate insulin dosage is depen-
`dent on the glycemic response of the in-
`dividual to food intake and exercise
`regimens. For virtually all type 1 patients
`and many type 2 patients, the time course
`of insulin action requires three or more
`injections per day to meet glycemic goals.
`Type 1 patients and some type 2 patients
`may also require both rapid- or short- and
`longer-acting insulins. A dosage algo-
`rithm suited to the individual’s needs and
`treatment goals should be developed with
`the cooperation of the patient. The timing
`of the injection depends on blood glucose
`levels, food consumption, exercise, and
`types of insulin used. Variables in insulin
`action (e.g., onset, peak, and duration)
`must be considered.
`Rapid-acting insulin analogs should
`be injected within 15 min before a meal or
`immediately after a meal. The most com-
`monly recommended interval between
`injection of short-acting (regular) insulin
`and a meal is 30 min. Eating within a few
`minutes after (or before) injecting short-
`acting insulin is discouraged because it
`substantially reduces the ability of that in-
`sulin to prevent a rapid rise in blood glu-
`cose and may increase the risk of delayed
`hypoglycemia. Guidelines should be set
`by the physician for the suggested interval
`between insulin injection and meal time
`based on factors such as blood glucose
`levels, site of injection, and anticipated
`activity during the interval.
`
`Self-monitoring
`Whenever possible, insulin-using pa-
`tients should practice self-monitoring of
`blood glucose (SMBG). Insulin dosage ad-
`justments should be based on blood glu-
`cose measurements. SMBG is extremely
`valuable in patients who take insulin be-
`cause they experience day-to-day vari-
`ability in blood glucose levels. This
`variability is influenced by differences in
`insulin absorption rates, insulin sensitiv-
`ity, exercise, stress, rates of food absorp-
`tion, and hormonal changes (e.g.,
`puberty, the menstrual cycle, menopause,
`and pregnancy). Illness, traveling, and
`any change in routine (e.g., increased ex-
`ercise and a different diet during vaca-
`tion) may require more frequent SMBG
`under the guidance of a physician. Travel
`through three or more time zones re-
`quires special advice regarding insulin
`administration. During illness, it is im-
`
`portant that insulin be continued even if
`the patient is unable to eat or is vomiting.
`When accompanied by hyperglycemia, a
`positive urine or blood test for ketones
`during illness indicates a need for extra,
`not less, insulin. Health professionals
`should obtain information regarding
`blood glucose values whenever patients
`need assistance in handling illness or stress.
`
`Hypoglycemia
`Excess insulin is a common cause of hy-
`poglycemia. Hypoglycemia may also re-
`sult from a delayed or missed meal,
`decreased carbohydrate content of a meal,
`increased physical activity, or increased
`insulin absorption rates (e.g., as a result of
`increased skin temperature due to sun-
`bathing or exposure to hot water). All
`insulin-requiring individuals should be
`instructed to carry at least 15 g carbohy-
`drate to be eaten or taken in liquid form in
`the event of a hypoglycemic reaction.
`Family members, roommates, school per-
`sonnel, and coworkers should be in-
`structed in the use of glucagon in those with
`type 1 for situations when the individual
`cannot be given carbohydrate orally. All
`insulin users should carry medical identi-
`fication (e.g., a bracelet or wallet card)
`that alerts others to the fact that the
`wearer uses insulin.
`
`SUMMARY — The injection of insu-
`lin is essential for management of patients
`with type 1 diabetes and may be needed
`by patients with type 2 diabetes for inter-
`mittent or continuous glycemic control.
`The species and dosage of insulin used
`should be consistent, and the patient’s in-
`jection technique should be reviewed pe-
`riodically with the diabetes care team. The
`effective use of insulin to obtain the best
`metabolic control requires an under-
`standing of the duration of action of the
`various types of insulin and the relation-
`ship of blood glucose levels to exercise,
`food intake, intercurrent illness, certain
`medications, and stress; SMBG; and
`learning to adjust insulin dosage to
`achieve the individualized target goals es-
`tablished between the patient, family, and
`diabetes care team.
`
`Bibliography
`American Diabetes Association: Continuous
`subcutaneous insulin infusion (Position State-
`ment). Diabetes Care 26 (Suppl. 1):S125, 2003
`American Diabetes Association: Resource guide
`2001. Diabetes Forecast (January):33–110, 2001
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`S124
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`©
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`DIABETES CARE, VOLUME 26, SUPPLEMENT 1, JANUARY 2003
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`Page 4 of 4
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`KOIOS Exhibit 1015