Diabetic Ketoacidosis & Hyperosmolar Hyperglycemic State- Inpatient management

1. Diabetic Ketoacidosis & Hyperosmolar Hyperglycemic State- Inpatient management Susan Schayes M.D., M.P.H. Division ChiefEmory Family Medicine, Emory University School of Medicine

2. High Impact Diseases / Jonas Brothers

3. Learning objectives • Define diagnostic criteria for diabetic ketoacidosis • Define diagnostic criteria for hyperosmolar hyperglyemia • Understand the five key components to the treatment algorithm

4. In 1552 BCDiabetes 1st Described In Writing • Earliest known record of diabetes mentioned on 3rd Dynasty Eqyptian papyrus by physician Hesy-Ra: mentions polyuria as a symptom. • 250 BC, Apollonius of Memphis coined the name "diabetes” meaning "to go through" or siphon. He understood that the disease drained more fluid than a person could consume. .

5. The Word Diabetes MellitusFirst Used • Gradually the Latin word for honey, "mellitus," was added to diabetes because it made the urine sweet. • Up to 11th century diabetes was commonly diagnosed by “water tasters” who drank the urine of those suspected of having diabetes, as it was sweet-tasting. .

6. Early Diabetes Discoveries • In the 1869, Paul Langerhans, a German medical student announced in a dissertation, that the pancreas contains two systems of cells. • 1889 Oskar Minkowski and Joseph von Mering in France, removed the pancreas from a dog to determine the effect of an absent pancreas on digestion

7. Fredrick Banting & Charles Best • Boss leaves on vacation May 1921 • Banting and his assistant Best isolate insulin from dogs, and give it to diabetic dogs. • Boss returns and is skeptical that insulin works • Try extract on themselves, then on:

8. Leonard Thompson The first patient to receive injections of pancreatic extract on January 11, 1922. He was 14. The young Toronto resident had been diabetic since 1919. He weighed only 65 pounds and was about to slip into a coma and die. At first he received Dr, F. Banting’s and Dr. Charles Best’s extract. Two weeks later he used the purified extract of Dr. J.B. Collip and Thompson's symptoms began to disappear; his blood sugar returned to normal and he was brighter and stronger. Thompson lived another 13 years with the insulin. He died at the age of 27 due to pneumonia, a complication of his diabetes

9. Type 1 vs. type 2 diabetesLambert P, et al. Medicine 2006; 34(2): 47-51Nolan JJ. Medicine 2006; 34(2): 52-56 • Features of type 1 diabetes • Onset in childhood/adolescence • Lean body habitus • Acute onset of osmotic symptoms • Ketosis-prone • High levels of islet autoantibodies • High prevalence of genetic susceptibility Features of type 2 diabetes • Usually presents in over-30s (but also seen increasingly in younger people) • Associated with overweight/obesity • Onset is gradual and diagnosis often missed (up to 50% of cases) • Not associated with ketoacidosis, though ketosis can occur • Immune markers in only 10% • Family history is often positive with almost 100% concordance in identical twins

10. Goals of management • Manage symptoms • Prevent acute and late complications • Improve quality of life • Avoid premature diabetes-associated death • An individualized approach Glycemic control BP Lipids Lifestyle (e.g. diet & exercise) Patient education Management Microalbuminuria & kidneys Eye care Foot care

11. Normal Physiologic Insulin Sensitivity and ­Cell Function Produce Euglycemia Normal Insulin Sensitivity Normal ­Cell Function Decreased Lipolysis Pancreas Liver Decreased Plasma FFA ↑ Glucose Uptake ↓ Glucose Production Islet ­Cell Degranulation;Insulin Released in Response to Elevated Plasma Glucose Muscle Adipose Tissue Decreased Glucose Output Normal Physiologic Plasma Insulin Increased Glucose Transport Euglycemia

12. ­Cell Dysfunction and Insulin Resistance Produce Hyperglycemia in Type 2 Diabetes Insulin Resistance ­Cell Dysfunction Increased Lipolysis Pancreas Liver Elevated Plasma FFA ↓Glucose Uptake ↑Glucose Production Islet ­Cell Degranulation;Reduced Insulin Content Muscle Adipose Tissue Increased Glucose Output Reduced Plasma Insulin Decreased Glucose Transport & Activity (expression) of GLUT4 Hyperglycemia

13. Diabetic Ketoacidosis: • Key features: hyperglycemia, ketosis, acidosis • Clinical presentation: polyuria, polydipsia, polyphagia, weakness, Kussmauls’respirations, nausea and vomiting • Can be mistaken for AGE

14. Diabetic Ketoacidosis Cause: reduced insulin levels, decreased glucose use, increased gluconeogenesis Primarily affects TIDM, but can be T2DM Precipitating factor: Infection, Noncompliance, Other acute event ie MI

15. Diabetic Ketoacidosis: • Treatment involves 5 key components: • Monitoring • Fluid resuscitation • Insulin and dextrose infusion • Electrolyte repletion • Treating underlying cause

16. Glucose Ketones Hyperglycemia Acidosis Glycosuria Osmotic Vomiting Diuresis Fluid & Electrolyte Depletion Renal Hypoperfusion Impaired Excretion of Ketones & Hydrogen ions PATHOGENESIS Ketoacidosis is a state of uncontrolled catabolism associated with insulin deficiency.

17. Polyuria leading to Oliguria • Dehydration, Thirst • Hypotension, Tachycardia, • Peripheral circulatory failure • Ketosis • Hyperventilation • Vomiting • Abdominal pain (acute abdomen) • Drowsiness, Coma CLINICAL FEATURES

18. METABOLIC FEATURES • Hyperglycemia • Glycosuria • Non-respiratory Acidosis • Ketonemia • Uremia • Hyperkalemia • Hypertriglyceridemia • Hemoconcentration

19. Glucose > 250 Arterial pH 7.25-7.30 Serum bicarb 15-18 mEq Urine and Serum ketones B-hydroxybutyrate- high Anion gap >10 Patient is alert Dx Criteria for Mild DKA Trachtenbarg David, Diabetic Ketoacidosis, American Family Physician, 2005;71:1705-1714

20. Glucose > 250 Arterial pH 7.00-7.24 Serum bicarb 10 to <15 mEq Urine and Serum ketones B-hydroxybutyrate- high Anion gap >12 Patient is alert/drowsy Dx Criteria for Moderate DKA Trachtenbarg David, Diabetic Ketoacidosis, American Family Physician, 2005;71:1705-1714

21. Glucose > 250 Arterial pH <7.00 Serum bicarb <10 mEq Urine and Serum ketones B-hydroxybutyrate- high Anion gap >12 Patient is stupor/coma Dx Criteria for Severe DKA Trachtenbarg David, Diabetic Ketoacidosis, American Family Physician, 2005;71:1705-1714

22. Glucose > 600 Arterial pH >7.30 Serum bicarb >15 mEq Urine and Serum ketones- small B-hydroxybutyrate- n or elevated Anion gap-variable Patient is stupor/coma- but can be awake Dx Criteria for HHS Trachtenbarg David, Diabetic Ketoacidosis, American Family Physician, 2005;71:1705-1714

23. DKA- Monitoring • ICU • 2 IV’s, Oxygen, cardiac monitor, continuous vitals, pulse ox • Foley to monitor I &O • Initially blood work every 1-2 hours • If pH is less that 6.9 be frightened

24. DKA- MonitoringStandard blood work • Glucose, lytes with calculated anion gap, Mag • Bun & creatinine, calculate GFR • Beta-hydroxybutyrate or serum ketones • UA • CBC • EKG • Infection-cultures,chest xray • Cardiac status-cardiac enzymes

25. DKA- Fluids • Deficits are typically 100 ml per kg • Fluid replacement will lower glucose • Initial Tx usually fluid, fluid, fluid • Initial resuscitation 15-20 ml/kg stat for severe dehydration with NS • 1l,1l,1l,then 500ml X4 hours, reassess/reassess (the pt not the computer) • Once glucose below 250, switch to D5W/.45% N saline

26. Insulin • Initially 10 units R Insulin IV, .15 units/kg • Insulin drip, most protocols 5-7 units per hour, .1 units/kg/hr • Patient to ICU • Stop insulin drip when sugar is less than 250-

27. Electrolytes- K • Whole body potassium deficits exist. (3-5 mmol/kg) • Acidosis increases K • Glucose + Insulin lowers K • Start K with K less than 5 mmol and adequate urine output • If initial K less than 3.3 mmol replete, and then start insulin when K above 3.3 mmol/L

28. Electrolytes- K • Commonly under repleted • Resident mistakenly uses the replacement of potassium protocol, which vastly under repletes potassium • Watch like a hawk!!!! • Replace/repete/replace/repete

29. Electrolytes- Mg • A serum deficit usually exists of .5-1 mmol per L • Consider repleting if less than 1.8 mg/dL

30. DKA & HONK Protocols- but use Common sense which is not common