Dijabetesna ketoacidoza (DKA) i neketotično hiperosmolarno stanje (NKHO) Section 4 | Part 2 of 2 Curriculum Module III–6 | Short-term complications Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) are two acute complications of diabetes. HHS used to be called hyperosmolar hyperglycaemic non-ketotic syndrome (HHNS or HONK). There is a comprehensive review of the subject by Kitabchi et al in Diabetes Care 2001. Slides current until 2008

Visoka glikemija, ketoni, acidoza i dehidracija Šta je DKA? Visoka glikemija, ketoni, acidoza i dehidracija Apsolutni ili relativni nedostatak insulina Povišen odgovor kontraregulatornih hormona Razgradnja masti i mišića Biohemijska trijada hiperglikemija ketoacidoza metabolička acidoza DKA occurs when a deficiency in insulin – either absolute or relative – prevents glucose from entering cells, which leads to increasing hyperglycaemia. The secretion of counter-regulatory hormones (glucagon, epinephrine, growth hormone and cortisol) resulting in a massive release of glucose from the liver, contributes to this hyperglycaemia. This is followed by the uncontrolled breakdown of adipose and muscle tissues (catabolism). Fatty acids are released and are rapidly metabolized into ketones, which have strong acidity, to act as an alternative fuel in the absence of glucose and insulin. The excessive production of ketones lowers the blood’s pH and leads to metabolic acidosis. DKA is characterized as the biochemical triad involving: Hyperglycaemia – normally blood glucose higher than 11mmol/L (191mg/dL) Excessive ketoacids in blood and urine Metabolic acidosis – pH below 7.3 Slides current until 2008

Smrt uglavnom zbog edema mozga Znatno češće kod tipa 1 dijabetesa Incidenca DKA Varira Smrt uglavnom zbog edema mozga Znatno češće kod tipa 1 dijabetesa Ponavlja se Može se javiti i kod tipa 2 dijabetesa The incidence of DKA varies across different communities depending to some extent on environment and people’s understanding of diabetes. In the USA, there are about five to eight episodes per 1000 people with diabetes. Incidence varies geographically and in different ethnic populations. In some areas, the overall incidence appears to be increasing, especially in low-income communities. Mortality due to DKA, usually through cerebral oedema, is thought to be less than 5% but this may be higher is some areas. DKA usually occurs in people with type 1 diabetes either at onset (up to 40% of newly diagnosed people with type 1 diabetes are in DKA) or in people with established diabetes. The average age of people with DKA is between 40 and 50 years; in 15% of people, there are recurrent episodes. When recurrent episodes occur, the underlying causes must be sought. DKA may occur in people with type 2 diabetes, sometimes at diagnosis. A person with type 2 diabetes with DKA can be treated initially as in type 1 diabetes until blood glucose levels drop and it becomes apparent that the person will be able to manage on diet and exercise and/or oral medication. DKA in people with pre-existing type 2 diabetes often occurs in conjunction with an infection or other illness. People become unable to manage increasing hyperglycaemia and polyuria; dehydration and DKA may develop. Kitabchi et al 2001, Joslin 2005 Slides current until 2008

DKA – uzrok ili okidač Incidenca Novonastali dijabetes 5-40% Akutno oboljenje 10-20% Izostavljanje insulina 33% Infekcija 20-38% Srčani udar, šlog, pankreatitis <10% As mentioned previously, the majority of cases of DKA occur at onset of type 1 diabetes as hyperglycaemia rises rapidly, catabolism escalates and acidosis develops. In some countries, the incidence may be as low as 5% to 10% of people with new-onset type 1 diabetes; in other communities this can be higher than 50%. It is important to look for the underlying causes or triggers of DKA. For example, if an illness or infection is the underlying cause, this must be treated. Insulin omission or poor adherence to the insulin regimen are now recognized as common causes of DKA, especially when multiple admissions to hospital occur. This may be due to poor finances, the inability to acquire insulin or a lack of understanding of the critical need for insulin. Insulin omission may also be intentional, most commonly in younger females trying to lose weight. Inadequate insulin levels leads to glycosuria (excretion of blood glucose in the urine) and subsequent weight loss. Attention to psychosocial status is one of the keys to diagnosis and must be addressed quickly before the situation becomes more complicated. A significant proportion of older people may have DKA as a complication of a heart attack or an infarction or other serious illness. Slides current until 2008 Booth 2001, Joslin 2005

Diabetesna ketoacidoza Nedostatak insulina Lipoliza Preuzimanje glukoze Slobodne masne kiseline Glicerol Hipergikemija Glikoneogeneza Ketogeneza Glikozurija Ketonemija Gubitak elektrolita Ketonurija Osmotska diureza This diagram shows the pathways in the development of DKA. The influence of counterregulatory hormones on gluconeogenesis and ketogenesis is not shown but is important. Note the osmotic diuresis that promotes the severe degree of electrolyte depletion and dehydration. DKA is the combination of dehydration and acidosis, both of which require treatment. Gubitak vode urinom Dehidratacija Acidoza Adapted from Davidson 2001 Slides current until 2008

Koriste se kao energetski izvor kada je smanjen kalorijski unos Ketoni Koriste se kao energetski izvor kada je smanjen kalorijski unos Ketoni se fiziološki javljaju kod gladovanja i produženog napora Nedostatak insulina  lipoliza i producija ketona  acidoza beta-hidroksibutirat acetoacetat aceton It is important to recognize the difference between mild physiological ketosis and the more serious pathological production of ketones in DKA. All of us have ketosis at times of fasting or when we are losing weight. In fact, some diet programmes require people to test for ketones in their urine to determine whether they are burning fat. This ketosis is physiological, does not represent a problem and does not cause illness. Note: the normal blood ketone level is less than 0.5mmol/L. In DKA, insulin deficiency leads to hyperglycaemia and the release of fatty acids from the breakdown (lipolysis) of fat stores. This produces excess ketones which are acidic – hence ketoacidosis. The three ketones produced are Beta-hydroxybutyrate which is the major ketone in the blood (and there are newer bedside methods of measuring this) Acetone (smelt on the breath and present in urine) Acetoacetate ( also excreted in the urine). Slides current until 2008

Ketoacidoza može postojati bez detektabilnih urinarnih ketona Ketoni Beta-hidroksibutirat predominira – ne detektuje se direktno test trakama Ketoacidoza može postojati bez detektabilnih urinarnih ketona Ketone u cirkulaciji treba određivati za ranu detekciju DKA The usual practice is to test urine for ketones (acetone and acetoacetate). Urine testing does not recognize beta-hydroxybutyrate, which is the main ketoacid in DKA. By the time urine tests positive for ketones, the level of beta-hydroxybutyrate may be quite high. Therefore, it is possible for a person to have DKA when the urine shows negative for ketones,. It should be remembered that ketonuria takes many hours to clear and is not a good indicator of a person’s well-being in the recovery phase of DKA. As blood ketones change more quickly, these enable the early detection of DKA and, compared to ketonuria, may be a better indicator of clinical progress as a person recovers from DKA. Blood testing is expensive and not available everywhere. Slides current until 2008

Rani klinički simptomi i znaci DKA Poliurija Polidipsija Polifagija Malaksalost Mišićni grčevi Zajapurenost lica The early symptoms of DKA are the same as those for increasing levels of hyperglycaemia – increased thirst and urination and, often, an increased appetite – to cope with the catabolic phase of diabetes. With regard to DKA, prevention is, of course, better than cure. The early recognition of these symptoms should alert us to a prompt diagnosis and urgent preventive treatment. Slides current until 2008

Kasni klinički simptomi i znaci DKA Gubitak telesne težine Mučnina i povraćanje Bol u trbuhu Dehidracija Acidotično disanje Hipotenzija Šok Poremećaj svesti Koma If the early signs are ignored, rapid weight loss – often more than 5 kg – results from increased lipolyisis and dehydration. By the time nausea and vomiting or abdominal pain develop, medical advice is required to either immediately adapt diabetes management in someone with established diabetes, or hospital treatment if new-onset diabetes is suspected. Acidotic breath (with acetone smell) occurs with the accumulation of CO2 due to shifts in acid base (very low pH and blood bicarbonate). At this stage, hospital treatment is a urgently required. Slides current until 2008

DKA – ispitivanje Neposredno za dijagnozu Kapilarna glikemija, glukoza i ketoni u urinu Hitno odrediti zbog daljeg lečenja Glikemija u krvi Gasovi u krvi Elektroliti, urea, kreatinin Leukociti i Le formula Razmotriti Monitoring srčane funkcije Hemokulturu, urinokulturu Rtg grafija pluća These are the laboratory and other assessments which should be carried out. Due to the metabolic acidosis, there is a shift of intra-cellular K+ to the extra-cellular fluid . Osmotic diuresis results in the loss of potassium. Therefore, people with DKA usually have an overall deficit of potassium. Cardiac monitoring is important in severe DKA to assess the possibility of heart attack as well as the ECG changes in hypoglycaemia or hyperkalaemia (excess potassium). Blood cultures should be performed to exclude underlying infection. Slides current until 2008

DKA – laboratorijski nalaze Glikemija >14mmol/L (252mg/dL) Ketoni Urin: umereno do dosta cirkulacija: >3mmol/L Osmolalnost Povećana – visoka glikemija i urea/kreatinin, dehdratacija Elektroliti Snižen/normalan Na+ i Cl- Snižen/normalan /povišen K+ (često dovodeći u zabludu) Sniženi HCO3 (normal 23-31) Anion gap >10 blaga >12 umerena do teška Gasovi u krvi pH <7.30, HCO3 <15 (blaga) pH <7.00, HCO3 <10 (teška) These are the results of clinical tests that may be seen in a person with DKA. Although ketoacidosis may be present with blood glucose levels within the normal range, blood glucose is usually above 14 mmol/l. As mentioned previously, there are total body deficits in potassium (K+). Sodium (Na+) will also be low. However, the lab results may be misleading because high lipid levels in a person with uncontrolled diabetes may spuriously lower sodium levels. Vascular dehydration plus the escape of potassium from cells often raises potassium levels. Treatment with insulin results in the rapid movement of potassium and glucose from the extra-cellular fluid back into the cells, thus potentially causing dangerous falls in potassium levels. In treatment, therefore, it is most important to correct shock and severe dehydration (with renal impairment in older people) before adding potassium and then insulin. Serum bicarbonate (HCO3) will be low. The lower the HCO3 or blood pH, the more severe the ketoacidosis. Slides current until 2008

DKA – terapija Rehidratacija 1. Korigovati šok bolusom elektrolitnih rastvora 2. Brzina rehidratacije zavisi od kliničkog statusa, životne dobi i funkcije bubrega. Fiziološki rastvor (0.9%) za inicijalnu reanimaciju i rehidrataciju Glukozno/elektrolitni rastvori kad glikemija bude oko 14 mmol/L (252mg/dL) Rehidrirati postepeno tokom 48 sati 3. Razmotriti nazogastričnu sukciju Kalijum Neophodan kada se posle početne reanimacije uspostavi diureza It has been shown that the prognosis is improved if a written protocol is available and followed meticulously. Fluid is essential in the initial treatment of DKA. This helps to reverse dehydration, which in turn reduces production of counterregulatory hormones. It also lowers blood glucose by improving renal perfusion. Shock and severe dehydration must be corrected first with normal saline (0.9%). The first litre of fluid is often delivered within the first 30 minutes. After this phase of resuscitation, the volume of fluid and the speed at which the fluid is administered depends on the clinical status of the person, as well as their age and overall osmolality – the higher the osmolality, the greater the need for caution during rehydration. It is now agreed that full rehydration should take place steadily over 48 hours. If vomiting persists (especially if consciousness is impaired) a nasogastric (NG) tube is advisable to empty and drain the stomach. As mentioned above, potassium replacement is essential to reduce the risk of hypokalaemia and cardiac arrythmia. Kitabchi et al 1976 Slides current until 2008

DKA – terapija Insulin Infuzija: 0.1 jedinica/kg/sat posle reanimacije, ustaljuje se infuzija elektrolta a glikemija pada Doza se povećava za 10-20% ako glikemija ne pada 2-3 mmol/L (45-54mg/dL) tokom prvog sata Monitoring Glikemija, krvni pritisak, diureza i satni neurološki nalaz Gasovi u krvi i elektroliti, u početku se kontrolišu na 2 sata It is now well accepted that a slow, steady infusion of insulin is ideal – often in adults after a bolus of 0.1 to 0.2 units/kg bodyweight. If not possible, however, hourly small injections of short-acting insulin is equally effective. The recommended insulin infusion dose is 0.1 unit/kg per hour. Blood glucose should be monitored frequently. If levels have not dropped by 2.5-3mmol/L (45-54mg/dl) in the first hour, the infusion rate should be increased. A rapid fall in blood glucose (greater than 5mmol/L) is associated with an increased risk of cerebral oedema. Therefore, frequent, close and expert monitoring is essential and should include assessment for fluid overload, headaches and changes in cerebral function. Slides current until 2008

Hipoglikemija +/- hipokaliemija DKA – komplikacije Hipoglikemija +/- hipokaliemija Ako se acidoza ne popravlja –razmotriti tešku dehirataciju ili infekciju Aspiraciona pneumonija Glavobolja +/- pad nivoa svesti –razmotriti edem mozga i hitno lečenje manitolom Although complications are not frequent, if these occur they are often serious and life-threatening. With slower insulin infusions, hypoglycaemia is now much rarer; with careful potassium monitoring, cardiac arrhythmias with hypogycaemia or hyperkalaemia should be avoided. The insertion of an NG tube to drain the stomach contents is very important in preventing continuing vomiting and aspiration pneumonia, especially in older people or those with impaired levels of consciousness. If cerebral oedema is suspected, immediate Mannitol infusion is recommended before considering cerebral imaging. Joslin 2005 Slides current until 2008

Nastaviti I.V. insulin sve dok postoji ketoza DKA – oporavak Poboljšanje je naglo Nastaviti I.V. insulin sve dok postoji ketoza Oralni unos čim bude moguće Brzodelujući insulin 30-60 minuta pre prekidanja I.V. insulina Uobičajeni režim davanja insulina Razmotriti davanje hrane i pića bogatih kalijumom Once treatment has been completed, people may show a rapid improvement, especially young children. It is important to maintain treatment while ketosis continues. Once alert, people should be started on oral fluids and food. Once ketosis is minimal, it is safe to start s/c short-/rapid-acting insulin which must be given 30-60 minutes before stopping the IV insulin infusion so that the s/c dose has time to be absorbed from the injection site. After a few injections of this insulin the patient may be moved onto the preferred insulin regimen. Potassium-containing drinks and food may be helpful to complete the process of replacing the entire deficit – especially if there has been some degree of previous malnutrition. Slides current until 2008

Prvenstveno kod starih osoba sa/bez podatka o tipu 2 dijabetesa Šta je NKHO stanje? Ketoza može postojati Koma ne postoji uvek Prvenstveno kod starih osoba sa/bez podatka o tipu 2 dijabetesa Uvek je povezana sa teškom dehidratacijom i hiperosmolarnim stanjem Razvija se u tokom nedelja As mentioned in slide 1, hyperosmolar hyperglycaemic state (HHS) used to be called hyperosmolar hyperglycaemic non-ketotic syndrome (HONK). It has been renamed because ketosis may be present to some degree. It is more of a state of altered consciousness when coma is not present. HHS is another complication of steadily increasing hyperglycaemia and polyuria – often with a concurrent infection. This usually occurs in older people, who are often unable to keep up with hydration and become progressively more confused and dehydrated. Blood glucose rises sharply due to decreased renal perfusion and the inability to excrete excess glucose. Kitabchi et al 2001 Slides current until 2008

HONK stanje – incidenca i osobine 0.5% prijema u bolnicu zbog dijabetesa ~15% stopa smrtnosti Može se dogoditi i kod mladih osoba i kod tipa 1 dijabetesa HHS is less common than DKA but the rate of mortality is much higher. There is often a delay in recognizing HHS because early symptoms may be mild. People do not reach the hospital until serious mental deterioration has already occurred. HHS can occur in people with type 1 diabetes and in younger people if there is sufficient insulin to prevent ketosis but insufficient to prevent dehydration. HHS occurs more rarely in younger people but has similarly serious implications due to hyperosmolality. Kitabchi et al 2001 Slides current until 2008

HONK stanje – glavne osobine Teška hiperglikemija Hiperosmolarnost Nedostatak teške ketoze Poremećena svest Blood glucose levels are sometimes very high. Because of this, coupled with serious dehydration, the blood becomes thicker and serum osmolality dangerously high. Urine ketones are usually negative or only mildly positive. Severely raised osmolality dehydrates the brain markedly and causes major changes in mental function. It is these changes and the treatment with fluids that make this ‘syndrome’ so dangerous. Joslin 2005 Slides current until 2008

HONK stanje – uzroci i okidači Incidenca Infekcija 40-60% Novonastali dijabetes 33% Akutno oboljenje 10-15% Lekovi, steroidi <10% Izostanak doze insulina 5-15% HHS is most often associated with an infection – sometimes seen in people who are newly diagnosed – especially type 2 diabetes. This happens more frequently in older people who have been increasingly tired and confused; it is frequently mistaken for signs of the aging process. Other illnesses and the use of medicines, such as steroids, diuretics, and anti-psychotics, have all been associated with cases of HHS. In some communities, insulin omission in type 2 diabetes has precipitated HHS as progressive hyperglycaemia has occurred without adequate hydration. Booth 2001 Slides current until 2008

Znaci i simptomi HONK stanja Inicijalno poliurija i polidipsija Poremećeno stanje svesti Teška dehidratacija Predisponirajući faktori Initial symptoms include polyuria and polydipsia. Urine output drops as the person becomes more dehydrated. The ability to recognize thirst may also decrease with altered mental status. This can make it difficult to obtain the person’s history. Family and friends may be important in supplying information about the person’s history over the previous few weeks. Profound dehydration leads to hypotension and tachycardia. It is important to recognize mental deterioration and dehydration in older people with type 2 diabetes. There may be precipitating factors which require treatment, such as: Infection Heart attack Stroke Pancreatitis. Slides current until 2008

HONK stanje – biohemijski nalazi Glikemija >33mmol/L (600mg/dl) Ketoni Urin: negativni – blago pozitivni Krv: <0.6 mmol/L Osmolarnost >320mOsm/kg - (povišeni Na, glukoza, urea) Elektroliti Povišen Na, glikemija, urea, kreatinin Anion gap <12 Gasovi u krvi pH >7.30 normalni ili povišeni HCO3 These are the serious biochemical results one would expect in a person with HHS. Although acidosis is not a typical feature, it does sometimes occur. Jones 2001 Slides current until 2008

Terapija Rehidratacija Oprezno! Fiziološki rastvor 1 l/sat inicijalno Razmotriti ½ fiziološki rastvor Kalijum Samo kod hipokaliemije i normalne bubrežne funkcije dati pre insulina Insulin Može biti potreban kao sprora infuzija 0.1 jedinica/kg/sat a zatim povećavati ako glikemija sporo opada Monitoring Glikemija, Krvni pritisak, neurološki znaci satno dok se stanje ne stabilizuje Elektroliti na 2 sata Srčana radnja i centralni venski pritisak In HHS, the first and foremost therapy is fluid replacement because of the severe dehydration. However, the speed of rehydration has been the subject of great debate; generally it is believed that the process should be slow and steady, probably with normal saline, to avoid excess fluid crossing the blood-brain barrier, causing cerebral oedema. There is also a risk of congestive heart failure. Therefore, fluid must be carefully replaced and monitored meticulously. Half-strength normal saline may be needed if sodium levels rise. Potassium and insulin are usually – but not always – needed as blood glucose falls successfully with improved hydration. Blood pressure and pulse should be monitored hourly to assess hydration. Monitoring of cardiac or central vein pressure (CVP) may also be of value. Slides current until 2008

HONK stanje– komplikacije Komplikacija Prevencija Hipoglikemija Dodavanjem infuzije glukoze ako je glikemija <14mmol/L (250 mg/dL) Hipokaliemija Rana nadoknada kalijuma uz monitoring Preterana rehidratacija Pažljiv klinički monitoring i centralni venski pritisak ako je potrebno Povraćanje/aspiracija Nazogastrična sukcija i postavljanje na stranu Edem mozga Izbegavati brz pad glikemije (trebalo bi <4mmol/L (72mg/dL) na sat; agresivna terapija manitolom kod ranih znakova edema mozga The treatment of both DKA and HHS have similar complications. Hypokalaemia is more likely in older people with poor nutrition, and when insulin is administered. Cerebral oedema is more of a risk in HHS than in DKA and carries a high risk of death. Clinical monitoring is of the utmost importance when looking out for further mental deterioration and signs of cerebral oedema – such as a rise in blood pressure, slowing pulse, irritability and headache. Urgent Mannitol may be required. Slides current until 2008 Meltzer 2004

DKA i HONK stanje – ključ je u prevenciji Otkriti i lečiti stanja koja ih mogu izazvati Može se prevenirati povećanjem svesti o problemu boljim pristupom zdravstvenoj zaštiti edukacijom o lečenju hiperglikemije tokom bolesti hitnom komunikacijom sa zdravstvenom službom The incidence of DKA and HHS can be reduced through improved awareness of diabetes and its early symptoms, and early intervention. All people with diabetes should be taught how to manage an episode of illness and to seek help if they are unable to manage their blood glucose levels. Families of elderly people with diabetes should be made aware of the symptoms of deteriorating diabetes control and instructed to seek help if concerned, especially if changes in behaviour occur. These may be due to either low or high blood glucose levels. Slides current until 2008

Evaluacioni test DKA Koje je od navedenih najvažnije ketonsko telo u DKA? Aceton Acetoacetat Beta-hidroksibutirat Nijedno od navedenih Slides current until 2008

Evaluacioni test DKA Koje je od navedenih najvažnije ketonsko telo u DKA? Aceton Acetoacetat Beta-hidroksibutirat Nijedno od navedenih Slides current until 2008

Evaluacioni test Koja karakteristika ukazuje pre na HKHO stanje nego na DKA? Ekstremna hiperglikemjia Ekstremni nedostatak insulina Veliki pad alkalne rezerve Zadah na aceton Slides current until 2008

Evaluacioni test Koja karakteristika ukazuje pre na HKHO stanje nego na DKA? Ekstremna hiperglikemjia Ekstremni nedostatak insulina Veliki pad alkalne rezerve Zadah na aceton Slides current until 2008

Evaluacioni test   3. Koja od navedenih strategija treba obavezno biti deo terapijske šeme osoba sa HKHO stanjem DKA? Insulinska terapija i nadoknada magnezijuma Moguća insulinska terapija i rehidratacija Insulinska terapija i rehidradacija Moguća insulinska terapija i nadoknada natrijum bikarbonata Slides current until 2008

Evaluacioni test   3. Koja od navedenih strategija treba obavezno biti deo terapijske šeme osoba sa HKHO stanjem DKA? Insulinska terapija i nadoknada magnezijuma Moguća insulinska terapija i rehidratacija Insulinska terapija i rehidradacija Moguća insulinska terapija i nadoknada natrijum bikarbonata Slides current until 2008

Evaluacioni test 4. Koja od navedenih strategija treba obavezno biti deo terapijske šeme osoba sa HKHO stanjem? Insulinska terapija i nadoknada magnezijuma Insulinska terapija i rehidradacija Moguća insulinska terapija i nadoknada natrijum bikarbonata Moguća insulinska terapija i rehidratacija Slides current until 2008

Evaluacioni test 4. Koja od navedenih strategija treba obavezno biti deo terapijske šeme osoba sa HKHO stanjem? Insulinska terapija i nadoknada magnezijuma Insulinska terapija i rehidradacija Moguća insulinska terapija i nadoknada natrijum bikarbonata Moguća insulinska terapija i rehidratacija Slides current until 2008

Evaluacioni test 5. Koji elektrolit je kritičan za monitoring kod DKA jer korekcija metaboličke acidoze može rezultirati srčanim aritmijama i mišićnom slabošću? a. Natrijum b. Kalijum c. Acetoacetat d. Beta-hidroksibutirat Slides current until 2008

Evaluacioni test 5. Koji elektrolit je kritičan za monitoring kod DKA jer korekcija metaboličke acidoze može rezultirati srčanim aritmijama i mišićnom slabošću? a. Natrijum b. Kalijum c. Acetoacetat d. Beta-hidroksibutirat Slides current until 2008

Answers c a d b Slides current until 2008

References – DKA and HHS Booth GL. Short-Term Clinical Consequences of diabetes. In H. Gerstein & RB Haynes (EDs.), Hamilton: BC Decker. Evidence-Based Diabetes Care 2001; 75-90. Jones H, Cleave B, Fredericks C, Hamilton C, Opsteen C. Building Competency in Diabetes education: the essentials. Canadian Diabetes Association, Canada, 2001. Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care 2001; 24(1): 131-53. Kitabchi AE, Ayyagari V, Guerra SMO. The efficacy of low dose versus conventional therapy of insulin for treament of DKA. Ann Int Med 1976; 84: 633-8. American Diabetes Association. Hyperglycemic crisis in patients with diabetes. Diabetes Care 2001; 26(S1): S109-17. Meltzer S, Yale JF, Belton AB, Clement M. Eds. Practical Diabetes Management; Clinical support for primary care physicians 5th ed. Canadian Diabetes Association, Canada, 2004. Davidson MB. Hyperglycemia. In: Franz MJ, ed. A Core Curriculum for Diabetes Education: Diabetes and Complications. 4th ed. Chicago: American Association of Diabetes Educators 2001; 23. Joslin’s Diabetes Mellitus. Eds Kahn CR,Weir GC et al. Publ Lippincott Williams & Wilkins, Philadelphia, 2005; 53. Generally speaking there are very good accounts of DKA and HHS in the bigger textbooks of diabetes, such as Joslin, but these other sources will be valuable. Slides current until 2008

References – managing illness Hyperglycemic crises in diabetes. ADA position statement. Diab Care 2004; 27 (Suppl 1). Hanas R. Type 1 diabetes in children, adolescents and young adults. 2nd edition 2004. Publ Class Publishing, London Laffel L, Pasquarello C, Lawlor M. Treatment of the child and adolescent with diabetes. Chap 35 in Joslin’s Textbook Diabetes. Publ Lippincott Williams & Wilkins, Philadelphia, 2005. Most references regarding sick days are found in the bigger or more practical text books (especially those dealing with children) or patient information packs published by ADA, CDA, DUK and pharmaceutical companies. A good exercise would be to design your own guidelines for practical, local use. Slides current until 2008