Insulin is required for normal carbohydrate, protein and fat metabolism. Patients with Type I diabetes depend on exogenous insulin for their survival while Type II diabetics may require insulin at a later stage of their disease.peer-reviewe

Tonna, Antonella

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22          thechronic✱ill     Issue 7 Summer 2003A history of insulinThe discovery of insulin in 1921 byBanting, Collip, MacLeod and Best was oneof the medical breakthroughs of thiscentury. These first insulins were of animalorigin, excreted from the pancreata of cowsand pigs. Addition of protamine and zincallowed the development of longer actinginsulins that were developed by 1951. By1972, insulins were purer and this madethem less immunogenic with a more reliableonset and duration of action. In the early1980s, genetic engineering allowed theproduction of insulin identical to humaninsulin by bacteria and yeast.1,2Indications for insulin therapyAll patients with Type I diabetes requirereplacement insulin therapy upon onset ofthe disease.3,4 Most patients with Type IIdiabetes initially secrete enough insulin tobe treated with diet, exercise and oralhypoglycaemic agents. However as thedisease progresses, the secretory capacityfalls making insulin treatment necessary.About 50% of patients require insulin dueto beta-cell exhaustion. Other indicationsfor insulin include pregnancy, ill healthprecluding oral treatment, during and aftermajor surgery, any illness that may placethe body in a stress situation, fasting bloodglucose of more than 17mmol/l ondiagnosis and diabetic ketoacidosis orhyperosmolar coma.3,5,6 The aims of treatment with insulin, arewhether Type I or Type II diabetes mellitusare:response to insulin.8,9 Since many patientsrequire a combination of intermediate orlong acting insulin with short actinginsulin, ready mixed insulin in the form ofbiphasic insulins are available.6Fast acting analogues (insulin lispro,insulin aspart), have been developed in anattempt to mimic physiology more closely.Conventional soluble insulin formshexamers when in solution. These need todissociate before absorption and thisdelays the onset of action. The neweranalogues are monomeric insulins and donot associate. These insulins start to actwithin 15 minutes of injection, peak at 50minutes and have a duration of action of 3-5 hours, which more closely resembleshuman insulin. They are thereforeadministered immediately before acarbohydrate meal and this is likely toenhance patient compliance.2,6,16All insulins available within the GHSare human in origin. The two forms ofbiosynthetic recombinant DNA insulinsusing Eschericia coli (Lilly) andSaccharomyces cerevisiae (Novo-Nordisk)are therapeutically equivalent.17 One shouldalso keep in mind that insulins fromforeign countries may be of animal origin.It is important that there is no inadvertentexchange of insulins. When in doubt,human insulin should be used.18All locally available insulins are of the100 unit strength implying that theycontain 100 units of insulin per millilitre(ml). Therefore care must be taken toinstruct the patient about the correct dosein units and not in millilitres (mls) ofinsulin. One must also exercise cautionwhen instructing tourists since differentstrengths of insulin may still be availableinternationally - 40 units/ml or 500 units/ml.17Designing insulin regimensThere is no generally acceptedapproach to initiating insulin therapy andmuch depends on the preferences of thediabetologist. An empiric way ofcalculating the dose may be the following:7A) Type I: Initial dose:0.5-0.8U/kgB) Type II: With ketosis, during illness: 1-1.5U/kgC) Type II: Adolescents in growth phase:1-1.5I/kgD) Type II: With insulin resistance:0.7-2.5U/kgDifferent dosing regimens may beadministered and these are tailoredaccording to the patient’s motivation, theability to monitor control and adjust dosesand the level of control desired.17 FactorsPart 3Diabetes Mellitus:Insulin UseSenior Clinical PharmacistSt. Luke’s Hospital, G’MangiaEmail: antonellatonna@hotmail.comAntonella Tonna B.Pharm. (Hons), MSc (Aberdeen)Insulin is required for normal carbohydrate, protein and fatmetabolism. Patients with Type I diabetes depend onexogenous insulin for their survival while Type II diabeticsmay require insulin at a later stage of their disease.a) to achieve optimum metabolic control bymimicking production of endogenousinsulin as closely as possibleb) to avoid experience and risks ofhypoglycaemia.4Types of insulinSince insulin is a protein that is actedupon by the gastrointestinal enzymes, itmust be administered parenterally. Insulinsmay be classified depending on theirpharmacokinetic profile into three types -short, intermediate and long acting.Regular insulin is a soluble, short-actinginsulin and since it is the only one availablein solution, it is the only insulin that maybe administered intravenously.6,7Intermediate and long acting insulins aresuspensions of insulin that have beenmodified to prolong absorption from thesite of administration. This is achieved byproducing insulin-protamine or insulin-zincmixtures. Insulin zinc mixtures may beamorphous or crystalline, with the latterhaving a longer duration of action.6,7 Theinsulins available within the GovernmentHealth Services (GHS) together with acomparison of their pharmacokineticcharacteristics are summarised in Table 1.When applying data linked topharmacokinetics, one must keep in mindthat most data were obtained throughassessment in healthy volunteers or in well-controlled diabetics under specificmetabolic conditions. In actual fact, thereis wide inter and intra subject variation inIssue 7 Summer 2003    thechronic✱ill         23that may alter the onset and duration ofinsulin action need to be considered. Thisincludes the site of injection (absorption isfastest from the abdomen and slowest fromthe thigh), ambient temperature (heatincreases the rate of absorption) andmassage of the local area (increases rate ofabsorption).7 Table 2 offers a comparison ofpossible insulin regimens.Administration of insulin via acontinuous subcutaneous infusion offersintensive glycaemic control but requirestraining, motivation and compliancetogether with supervision from anexperienced healthcare team. Such a systemprovides a basal amount of insulin (0.5-1unit/hour) and patient-activated pulsatiledoses of insulin to cover meals. Pumptherapy may increase patient flexibility butit is coupled by numerous problems such asmechanical failure and hypoglycaemic anddermatological complications. Besides, thereis no evidence that this intensive insulintherapy offers better control than multipledosing.7 Patient selection criteria aretherefore cardinal to ensure safety andsuccess of treatment.The sliding-scale method of insulindosing is sometimes used in a hospitalsetting where insulin requirements may varydrastically over a short period of time dueto stress, variable calorie intake orinactivity. Capillary blood glucoseconcentrations are measured every 4-6hours and insulin administered accordinglyas prescribed. Sliding scales vary frominstitution to institution and according tothe patient response. One needs to ensurethat the personnel involved are adequatelyrisk or degree of hypoglycaemia such asmissing meals, having smaller mealsthan usual, increasing alcohol intake ora sudden increase in physical exercise.They should also be instructed onmanagement including the readyavailability of oral glucose if stillconscious and administration ofglucagons by relatives or companions ifunconscious.4,6 Hypoglycaemicunawareness may be a problem inpatients who have been on insulin for along time or are on beta-blockertreatment. Such patients should beencouraged to monitor blood glucosefrequently. Despite reports that thisphenomenon is increased whenchanging from animal to human insulin,there is no evidence to support this.4,7• Dermatological complicationsinclude lipoatrophy (more common inwomen), lipohypertrophy (more common inmen) and local skin reactions. Rotation ofinjection site, use of human insulin and useof a pure form of insulin reduces suchcomplications.7,17Newer therapiesResearch is currently underway toexploit different delivery routes for insulin.Inhaled insulin is an option where insulin isabsorbed over the lung alveolar surface.However the bioavailability is only 10%making this an expensive alternative.Absorption is also very erratic withconsiderable variation betweenindividuals.2,21 The possibility of deliveringinsulin transdermally is also beingresearched.22trained in bedside blood glucosemonitoring and that meters are properlymaintained and calibrated. Strips shouldbe kept in tightly sealed containers toprevent deterioration.7A dosage regimen may involvecombination of insulin with oral agentsand this may be an option in Type IIdiabetics where glycaemic control is notadequate. Insulin is normally administeredas a dose at night to suppress the hepaticglucose output.5 The reader is referred topart 2 of this series for a more detaileddiscussion.19Patients may present to the pharmacywith nausea and vomiting due toconditions such as viral gastritis. It is veryimportant to advice the patient tomaintain the same dose of insulin despiteminimal food intake and advise thepatient to seek specialist medical adviceimmediately. At no point should such apatient be advised to stop insulin sincethis may precipitate ketoacidosis.Adverse effects associated with insulintherapyParticular problems that one needs tolook out for include:• Hypoglycaemia may be a particularproblem in drivers and other high riskoccupations. Patients usually becomeaware of dysfunction when glucoselevels fall below 3.5mmol/l. This maybe avoided by individualising thedosage regimens, educating thepatient and regularly reviewing drugregimens. Patients should be educatedto avoid factors that may increase the1 All Novo products - biosynthetic recombinant DNA origin produced in Saccharomyces cerevisiae2 All Lilly products - biosynthetic recombinant DNA origin produced in Eschericia coliType Brand name Active Ingredient Manufacturer Onset (hr) Peak (hr) Duration (hr) AppearanceShort ActingActrapid (10) Soluble insulin Novo Nordisk1 0.5-1 2-4 5-7 ClearHumulin R (11) Soluble insulin Lilly2 0.5-1 2-4 5-7IntermediateMonotard (12) Mixture of Zinc amorphous & Novo Nordisk within 0.5 7-15 24 Cloudycrystalline particles ratio 3:7Humulin N (11) Crystalline suspension Lilly within 0.5 4-12 24 Cloudyof human insulin withprotamine and zincInsulatard (13) Isophane insulin Novo Nordisk within 0.5 4-12 24 CloudyLong ActingUltratard (14) Suspension of insulin Novo Nordisk 4 8-24 28 Cloudyzinc crystalline particlesBiphasicMixtard 70/30 70% isophane Novo Nordisk within 0.5 2-8 24 Cloudy(15) 30% solubleHumulin 70/30 As above Lilly within 0.5 2-8 24 Cloudy(11)Table 1: Characteristics of insulins currently available within the Government Health Services 6,724          thechronic✱ill     Issue 7 Summer 20031. Discovery of insulin.com website.www.discoveryofinsulin.com. Accessed onMarch, 3rd, 2003.2. Amiel Stephanie. Is there anything newabout insulin therapy? In: Amiel S, editor.Horizons in Medicine. Number 13. London.Royal College of Physicians; 2002.3. Bahttacharyha A. Aetiology and Pathology ofType 2 Diabetes Mellitus. Hospital Pharmacy2001: 8:5-9.4. International Diabetes Federation on behalfof the St. Vincent Declaration initiative ofIDF (Europe)/WHO. Consensus Guidelines forthe Management of Insulin-Dependent (TypeI) Diabetes. Available at:www.staff.ncl.ac.uk/philip.home/iddmch3.htm. Accessed on March, 3rd, 2003.5. Bahttacharyha A. Treatment of Type 2Diabetes Mellitus. Hospital Pharmacy 2001:8: 10-17.6. British Medical Association and RoyalPharmaceutical Society of Great Britain.British National Formulary. September 2002.Available at: www.bnf.org. Accessed on:March, 3rd, 2003.References7. Koda-Kimble Mary Anne, Carlisle Betsy A.Diabetes Mellitus. In: Young LY, Koda-KimbleMA. Applied Therapeutics: The clinical use ofdrugs. 6th edition. Vancouver. AppliedTherapeutics. 1995.8. Binder C. Insulin Pharmacokinetics. DiabetesCare. 1984; 7:188.9. Zinman B. The physiologic replacement ofinsulin. An elusive goal. NEJM. 1989;321:363-70.10. Electronic Medicines Compendium for theProfessional. Specific Product Characteristics.Actrapid. 2001. Available at:www.emc.vhn.net/professional. Accessed on:March, 12th, 2003.11. Drug Information by RxList - Drugs andMedications. www.rxlist.com/cgi/generic/huminsr.htm. Accessed on March, 12th, 2003.12. Electronic Medicines Compendium for theProfessional. Specific Product Characteristics.Monotard. 2001 Available at:www.emc.vhn.net/professional.    Accessedon: March, 12th, 2003.13. Electronic Medicines Compendium for theProfessional. Specific Product Characteristics.Insulatard. 2001. Available at:www.emc.vhn.net/professional. Accessed on:March, 12th, 2003.Table 2: Comparison of methods of insulin dosing 2,5,6,17Time of insulin 7am: before 11am: before 6pm: before Commentsadministration breakfast  lunch dinnerSingle injection - Total dose Least efficient to control glucose.Intermediate acting Most likely to result in hyperglycaemiabefore dose, and hypoglycaemia at peakinsulin effect. Should be reserved only forelderly patients.Two daily injections 2/3 1/3 Better than above. Assumes that 2/3of intermediate acting of calorie intake at breakfast and lunch.Two doses of fixed 2/3 1/3 Provides average control. Usually 70/30biphasic insulin mixture of intermediate/short actingused. Allows change in units but not ratio.Two doses of biphasic insulin 2/3 1/6 short acting Provides above-average control.where ratios may be altered 1/6 intermediate Allows change in both units andratio of mixture of insulins used.Split regular with long acting 1/5 short 1/5 short 1/5 short Provides excellent glucose control but2/5 intermediate requires patient motivation. Use oneor long or two intermediate long acting dosesto provide background levels andregular insulin doses before each meal.The role of transplantation in Type Idiabetes is an interesting feature with thefirst pancreatic transplantation beingcarried out in 1996. An overall one-yearpatient survival rate of 90% and graftsurvival rate of 82% has been reported.Selective Islets of Langerhans celltransplantation is another option thatappears more attractive since it involvesonly a minor surgical procedure. The numberof cells available would be larger than awhole pancreas.2,5,7  Problems associatedwith transplantation include lack ofpancreatic donors, the need for lifelongimmunosuppression and the use of steroidsin the post-transplant period.Transplantation is therefore limited to TypeI diabetics only when conventional therapysignificantly fails.Though there have been numerousdevelopments to produce newer insulins andalternative therapies that are moreconvenient for the patient to use, it appearsthat more progress is required to makeoptimal use of the insulins that arecurrently available.14. Electronic Medicines Compendium for theProfessional. Specific Product Characteristics.Ultratard. 2001. Available at:www.emc.vhn.net/professional. Accessed on:March, 12th, 2003.15. Electronic Medicines Compendium for theProfessional. Specific Product Characteristics.Mixtard 70/30. 2001. Available at:www.emc.vhn.net/professional. Accessed onMarch, 12th, 2003.16. Campbell KR., Campbell LK, White JR. InsulinLispro: its role in the treatment of diabetesmellitus. Annals of Pharmacotherapy. 1996;30: 1263-1269.17. White John R., Campbell KR. Diabetes Mellitus.In: Herfindal ET, Gourley DR. Textbook ofTherapeutics: drug and disease management.6th Edition. USA. Williams and Wilkins. 1996.18. American Diabetes Association: ClinicalPractice Recommendations. InsulinAdministration. Diabetes Care. 2001; 24 (S1).19. Tonna A. Management of Type II DiabetesMellitus - Part 2. The Chronicill. 2002;6: 5-9.20. Dixon N. Pharmacists as part of an extendeddiabetes team. PJ. 2002; 268: 469-470.21. White JR, Campbell KR. Inhaled insulin: Anoverview. Clinical Diabetes 2001;19: 13-16.22. Medicine in the making: Insulin via a skinpatch? Health Horizons 1996; 27:18.

Association: Clinical Practice Recommendations. Insulin Administration. Diabetes Care.

Diabetes Mellitus. In: Herfindal ET, Gourley DR. Textbook of Therapeutics: drug and disease management. 6th Edition.

Diabetes Mellitus. In: Young LY, Koda-Kimble MA. Applied Therapeutics: The clinical use of drugs. 6th edition. Vancouver. Applied Therapeutics.

Drug Information by RxList - Drugs and Medications. www.rxlist.com/cgi/generic/ huminsr.htm. Accessed on

Electronic Medicines Compendium for the Professional. Specific Product Characteristics. Actrapid.

Electronic Medicines Compendium for the Professional. Specific Product Characteristics. Insulatard.

Electronic Medicines Compendium for the Professional. Specific Product Characteristics. Mixtard 70/30.

Electronic Medicines Compendium for the Professional. Specific Product Characteristics. Monotard.

Electronic Medicines Compendium for the Professional. Specific Product Characteristics. Ultratard.

Inhaled insulin: An overview.

Insulin Lispro: its role in the treatment of diabetes mellitus. Annals of Pharmacotherapy.

Insulin Pharmacokinetics. Diabetes Care.

Management of Type II Diabetes Mellitus - Part 2. The Chronicill.

Medicine in the making: Insulin via a skin patch? Health Horizons

Pharmacists as part of an extended diabetes team.

The physiologic replacement of insulin. An elusive goal.

Diabetes Mellitus : Insulin use

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Diabetes Mellitus : Insulin use

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