Diabetes is one of the most prevalent chronic disorders worldwide. By 2010, the number of people with diabetes is expected to exceed 350 million1. Diabetic complications cause considerable morbidity in 5- 10% of these patients, with diabetic complications accounting for 4% of hospital admissions2. Malta is no exception with statistics gathered in 1987 indicating that 10% of adults aged 35 and over had diabetes while another 13% had impaired glucose tolerance (IGT). This problem is found in other Mediterranean island communities (Cyprus, Sardinia, Sicily, Pantelleria) where a prevalence of 5% is found3. Opportunities for interacting with the diabetic patient are numerous and the pharmacist is ideally positioned to intervene with the aim of optimising patient treatment. This review will deal with a brief pathophysiology of diabetes and its complications, a good knowledge of which is fundamental since it leads to a clear understanding of the factors to be considered when choosing the appropriate therapy for the individual patient.peer-reviewe

Tonna, Antonella

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16          thechronic✱ill     No 5 Summer 2001Senior Clinical Pharmacist, In-Patient Dispensery, St. Luke’s Hospital G’Mangaemail: antonellatonna@hotmail.comAntonella Tonna   B.Pharm. (Hons.), PgD (Aberdeen)Key words: diabetes mellitus, insulin, type I diabetes, type II diabetes,impaired glucose tolerance,Diabetes Mellitusand its ManagementAn Introductory OverviewDiabetes is one of the most prevalent chronic disorders worldwide. By2010, the number of people with diabetes is expected to exceed 350million1. Diabetic complications cause considerable morbidity in 5-10% of these patients, with diabetic complications accounting for 4%of hospital admissions2. Malta is no exception with statisticsgathered in 1987 indicating that 10% of adults aged 35 and over haddiabetes while another 13% had impaired glucose tolerance (IGT).This problem is found in other Mediterranean island communities(Cyprus, Sardinia, Sicily, Pantelleria) where a prevalence of 5% isfound3. Opportunities for interacting with the diabetic patient arenumerous and the pharmacist is ideally positioned to intervene withthe aim of optimising patient treatment. This review will deal with abrief pathophysiology of diabetes and its complications, a goodknowledge of which is fundamental since it leads to a clearunderstanding of the factors to be considered when choosing theappropriate therapy for the individual patient.Part 1 Pathophysiology, Classification,Diagnosis and ComplicationsBack to BasicsDefinition of diabetesDiabetes mellitus may be defined asa clinical syndrome characterised byhyperglycaemia due to absolute orrelative deficiency of  insulin4. If nottreated, diabetes may lead to acutehyperglycaemia (diabetic ketoacidosis(DKA) or non ketotic hyperosmolarcoma) and, if long-standing, to latecomplications leading to a reduced lifeexpectancy.How does insulin maintaina normal blood glucose?Following food intake, ahomeostatic mechanism comes intoplay which ensures that food isappropriately stored for later use. Inresponse to food ingestion and theensuing direct stimulatory effect ofglucose and amino acids on pancreaticß cells, insulin is secreted. Thispromotes carbohydrate uptake by theliver and muscle for glycogen synthesis,carbohydrate uptake by adipose tissuefor triglyceride synthesis, amino aciduptake into liver and muscle andtriglyceride uptake by adipose tissue.Throughout, insulin acts as an‘anabolic’ hormone, that is, it promotessynthesis of protein, glycogen andtriglycerides and prevents theirbreakdown into the respective subunits.In the fasting state, mobilisation ofstored energy is necessary and this isaccomplished by:1.  reduced insulin secretion resultingin the release of glucose fromglycogen stores in the liver andmuscle2.  increased lipolysis during whichtriglycerides are broken down intofree fatty acids. This is enhanced byglucagon and other counter-regulatory hormones.No 5 Summer 2001    thechronic✱ill         17Table ICharacteristic Features of Type I and Type II diabetes(2,6)Feature Type I diabetes Type II diabetesPrevalence • 5-10% of diabetic population 90% of all diabeticsAge of onset • usually less than 30 years • usually over 40 yearsPancreatic function • no residual or very little • retain some pancreatic functionpancreatic functionAetiology • though exact aetiology is unknown, • involves defects in insulin secretion,presence of islet cell antibodies resistance to insulin, hepatic glucose outputindicate an autoimmune functionFamily history • generally not strong • strong family historyObesity • commonly not obese • commonly obeseOnset • usually sudden and patients • insidious and diagnosed duringpresent with ketoacidosis routine examinationWhat happensif there is a lack of insulin?When insulin secretion  is lacking,one observes:1.  a breakdown of stored triglyceridesand proteins resulting in catabolismand the characteristic weight lossseen in uncontrolled diabetes2.  an excessive production of ketonebodies leading to metabolicacidosis. This results in DKA - anacute decompensated state whichshould be treated as a medicalemergency4,5.Classification of diabetes.The following is an overview of theclassification of diabetes :A.  Primary diabetes: implying thatno underlying disease is present• Type I: previously known as insulindependent diabetes mellitus (IDDM)or juvenile diabetes• Type II: previously known as non-insulin dependent diabetes mellitus(NIDDM) or adult-onset diabetes• MODY: maturity onset diabetes ofthe youngB.  Gestational diabetes: defined ashyperglycaemia which is firstdiagnosed during pregnancy (thatis, not in a previously knowndiabetic)Diagnosis and treatment  areimportant since the excess maternalglucose crossing the placenta mayresult in excess foetal insulin secretion.This, in turn, may cause foetalmacrosomia and increase the risk ofbirth trauma, may necessitateCaeserean section and may lead toneonatal hypoglycaemia. Women withgestational diabetes often developdiabetes within five years post partum4.C.  Secondary diabetes: implyingdiabetes secondary to anunderlying pathology• Malnutrition related diabetes• Secondary to pancreatic disease -for example, chronic pancreatitis: acommon cause is alcoholism wherebeta cell mass is destroyed6; cysticfibrosis; neoplastic disease• Secondary to endocrine disease -often involves excess endogenousproduction of hormonal antagoniststo insulin4,6: for example,phaeochromocytoma; acromegaly;Cushing’s syndrome; ‘stresshyperglycaemia’ following severeburns, acute myocardial infarctionand other life threatening illnesses(due to endogenous release ofglucagon and catecholamines)• Drug induced - for example,corticosteroids, loop and thiazidediuretics; phenytoin• Insulin receptor dysfunctionality -hyperglycaemia occurs due toquantitative or qualitative defectsin the insulin receptor or toantibodies directed against it1,6.• Inherited disorders - (diabetes plus)for example, muscular dystrophies;Down’s syndrome; Turner’ssyndrome7.• Non-endocrine disorders - forexample, renal failure and hepaticfailureType I and Type II diabetes are themost commonly encountered forms ofdiabetes and consequently, this reviewwill focus mainly on these two types.Since the approach to management and18          thechronic✱ill     No 5 Summer 2001treatment is somewhat different, anunderstanding of the main features ofeach one and the differences betweenthe two is crucial.Table 1 summarises the maincharacteristic features of Type I andType II diabetes1,6:What  are  the signs andsymptoms of diabetes?It is of primary importance that thepharmacist has a good understandingof commonly presenting signs andsymptoms of diabetes since patientsmay present at the communitypharmacy with such ailments.In the Type I patient, the onset ofthe disease is sudden with profoundweight loss (despite increased intakeof food), severe fatigue, polydipsia(thirst) and polyuria (frequenturination) 5,8. Such patients should bereferred immediately since acutemetabolic decompensation is imminentand patients normally requirehospitalisation.Patients with Type II present withless severe symptoms - fatigue,polyuria and vaginal and urinary tractinfections. However, the onset of TypeII is often a gradual process and veryoften the ‘classic’ symptoms are notapparent. Therefore, patients maypresent when complications of diabeteshave occurred8. It is therefore veryimportant to encourage patients athigh risk to undergo screening testswith emphasis on fasting and randomblood glucose levels.The World Health Organisationcriteria for the diagnosis of diabetesmellitus are5,9:1.  A fasting blood glucose of >7.8mmol/l preferably obtained on tworepeated occasions or a randomblood glucose of >11.1 mmol/l ontwo repeated occasions2.  A two hour glucose level of 11.1mmol/l or more during an oralglucose tolerance test. When thetwo hour value is between 7.8 and11.1 mmol/l, the patient isdiagnosed as having IGT. Thisimplies that the patient is:• at an increased risk of developingdiabetes• at an increased risk of developingatherosclerotic disease.When IGT is diagnosed, managementis directed toward avoidance ofdiabetes and arterial disease - follow upwith blood glucose tests is imperative.At this point, it is appropriate tomention urine testing for glucose.Unfortunately, there is a popularlocal belief that urine testing forglucose is “THE TEST” to use todiagnose and monitor diabetes. Urineglucose concentrations correlate poorlywith blood glucose concentrations andtherefore should only be used forpatients who cannot or refuse to testblood. In the healthy individual, a bloodglucose of 15 mmol/l or over is requiredfor a urine glucose test to be positive.Besides, the renal threshold for glucosemay be decreased, as in pregnancy orwhen other sugars are present in theurine, or increased in the elderly. Thisresults in false positive or false negativetests implying that urine testing is nota reliable method5.Why is it important tomaintain normal glucoselevels?The main aim of trying to achieveeuglycaemia (normal blood glucoselevels) is to prevent development ofacute complications and to delayprogression of the disease. Publishedstudies have provided evidence thattight glycaemic control is associatedwith reduced complications both in TypeI and Type II. The Diabetes Control andComplication Trial (DCCT) has clearlyshown this in Type I diabetes10 whilethe UK Prospective Diabetes Study(UKPDS) has shown this in Type IIdiabetes11. The latter is the longest andlargest study in the history  of  diabetesand has clearly shown that tight controlproduced a 25% reduction ofmacrovascular complications9.The main chroniccomplications of diabetesA.  Macrovascular disease: This leadsto an increased risk of coronaryheart disease and is the major causeof increased mortality in diabeticpatients accounting for about 70%of all deaths4. Risk factors forcoronary heart disease (for example,smoking, hypertension andhypercholesterolaemia) have to beminimised in a diabetic patientsince risk factors are additive5.B.  Diabetic microangiopathy: This isa disease of the small vesselsspecific to diabetes. It is the maincause of morbidity in the diabeticpatient. Diabetes first induces astructural abnormality in the bloodvessel with an increase in basementmembrane thickness. Thisconsequently leads to a functionalabnormality with increasedpermeability of the blood vessels tofluid and molecules such asalbumin10. Though all blood vesselsare affected, three specialisedregions are at particular risk:• the kidney, leading to diabeticnephropathy• the eye, leading to diabeticretinopathy and blindness• the nerve sheath, leading todiabetic neuropathy in turn leadingto a loss of sensation and increasedrisk of injury.The acute complicationsof diabetesA.  Diabetic ketoacidosis (DKA): ametabolic acidosis which occurs dueto  excess synthesis of ketonebodies as a result of insulindeficiency. As already explainedabove, an insulin deficiency resultsin a catabolic state wheretriglycerides are broken down intofree fatty acids. These are taken upNo 5 Summer 2001    thechronic✱ill         19References:1. Serupalle, Madsen Ole D., Mandrup-Poulsen Thomas. Islet celltransplantation for treating diabetes.BMJ 2001;322:29-32.2. Salman Hussein. Type I DiabetesMellitus - Prognosis and Complications.Modern Medicine of the Middle East1994;11:86-92.3. The Health of the Maltese Nation.Official website of the MalteseGovernment. www.magnet.mt/services/health.4. Edwards CRW., Bouchier IAD. andHaslett C. Davidson’s principles andpractice of medicine. 9th Edition. GreatBritain: Churchill Livingstone; 19965. Souhami RL and Moxham J. Textbook ofmedicine. Great Britain: ChurchillLivingstone; 19906. Fauci AS, Braunwald R, Isselbacher KJ,Wilson JD, Martin JB, Kasper DL, HauserSL and Longo DL. Harrison’s Principles ofInternal Medicine. 14th Edition. USA:McGraw Hill; 1998.7. Pearson ER and Hattersley AT. Diabetes.JR Coll Physicians London 2000;34:332-5.8. National Prescribing Centre. MerecBulletin, 1996;7:21-24.9. Bhattacharya DM. Aetiology andpathology of type 2 diabetes mellitus.Hospital Pharmacist 2001;8:5-17.10. The Diabetes Control and ComplicationsTrial (DCCT) research group. Effect ofintensive diabetes management onmacrovascular events and risk factors inthe diabetes control can complicationstrial. Am J. Cardiol 1995;75:894-903.11. UK Prospective Diabetes Study Group.Intensive blood glucose control withsulphonylureas or insulin compared withconventional treatment and risk forcomplications in patients with type 2diabetes (UKPDS 33). Lancet1998;352:837-53.12. Hope RA, Longmore JM, Hodgetts TJ andRamrakha PS. Oxford Handbook ofClinical Medicine. 3rd Edition. UnitedStates: Oxford University Press; 1996.by the liver together with alanine,lactate and glycerol to synthesiseacidic ketone bodies, acetoacetateand 3-hydroxybutyrate.Accumulation of these substancesleads to a metabolic acidosis. Thepatients normally present withprofound dehydration,hyperventilation, vomiting andsometimes abdominal pain.Management involves:• Fluid replacement in the form of0.9% normal saline• Electrolyte replacement• Insulin replacement usually in theform of a continuous intravenousinfusion5.Within the local state hospital, allDKA patients are admitted on wards M5and M6. A written protocol for thetreatment of DKA is present on thewards and ensures that management isstandardised.B.  Non-ketotic hyperosmolar coma:This usually occurs in older patientsand normally affects patients withType II. It occurs when uncontrolledhyperglycaemia leads todehydration, increased osmolalityand ultimately coma. However,ketosis does not develop since someresidual insulin activity inhibits theperipheral lipolysis occurring in DKAand ketone production is thereforesuppressed. Patients normallypresent with profound dehydrationand a reduced level ofconsciousness. Management issimilar to that for DKA with theexception of the following :• Fluid replacement is in the form of0.45% Normal saline• Insulin replacement is usually less• Due to the high risk of thrombosis,heparin treatment is instituted12.C.  Hypoglycaemia: This fall in bloodglucose is often related totreatment issues in Type I and TypeII patients. This will be discussed indetail later on in the series.  ✱

Aetiology and pathology of type 2 diabetes mellitus.

Davidson’s principles and practice of medicine. 9th Edition. Great Britain: Churchill Livingstone;

Hodgetts TJ and Ramrakha PS. Oxford Handbook of Clinical Medicine. 3rd Edition. United States:

Islet cell transplantation for treating diabetes.

Textbook of medicine. Great Britain: Churchill Livingstone;

The Health of the Maltese Nation. Official website of the Maltese Government.

Type I Diabetes Mellitus - Prognosis and Complications.

Diabetes Mellitus and its management : an introductory overview

https://www.um.edu.mt/library/oar/bitstream/handle/123456789/13313/2001-5-6.pdf?sequence=1&isAllowed=y

Diabetes Mellitus and its management : an introductory overview

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