1. Diabetic Ketoacidosis

2.  An anion gap acidosis due to severe insulin deficiency and excess of counterregulatory hormones

3. Insulin Deficiency  Insulin is required for efficient transport of glucose into muscle, adipose, and liver cells  Proper utilization of glucose within liver cells is also dependent on insulin  In the absence of insulin glucose cannot be effectively transported into cells and it accumulates in the blood  The liver begins to manufacture glucose from amino acids (gluconeogenesis)  Additional glucose is thus secreted into the bloodstream

4. Insulin Deficiency: Effects on the Kidney  When the degree of hyperglycemia exceeds the kidney’s capacity for tubular reabsorption glucose appears in the urine  Osmotic diuresis ensues and the patient develops polyuria  Severe dehydration may result

5. Insulin Deficiency: Effects on Lipolysis  Under normal circumstances insulin inhibits lipolysis  In the absense of insulin adipose cells degrade their stores of triglycerides into fatty acids  Fatty acids are converted by the liver into ketone bodies (acetoacetate and b-hydroxybutyrate)  A metabolic acidosis develops

6. Actions of Glucagon  Glucagon when unopposed by normal insulin is responsible for the hepatic components of diabetic decompensation  Increased glycogenolysis  Increased gluconeogenesis  Increased ketogenesis

7.  Insulin deficiency causes augmented delivery to the liver of substrates for glucose and ketone production  Glucagon is the switch that activates the hepatic production machinery for glucose and ketones

8. Precipitating Factors in DKA  Failure to take insulin  Failure to increase insulin during acute illness, infection  Other intercurrent illness such as myocardial infarction, pancreatitis, stroke, trauma or severe emotional stress  The counterregulatory hormones released during medical stress oppose insulin and stimulate glucagon release  Hypovolemia increases the secretion of glucagon, catecholamines by decreasing renal blood flow and this further reduces glucagon degradation by the kidney

9. Signs and Symptoms of DKA  Polyuria and polydipsia  Kussmaul hyperventiation  Vomiting and abdominal pain  An acetone odor to breath  Dehydration  Stupor and coma

10. Initial Lab Findings  Hyperglycemia  Anion gap acidosis  Positive urine and serum ketones  Hyperosmolarity

11. Differential Diagnosis  Anion gap acidosis: (Na + K) - (Cl +Bicarb) >16  Alcoholic ketoacidosis  Lactic acidosis  Renal failure  Ethylene glycol or methyl alcohol poisoning  Starvation in late pregnancy or lactation (rare)

12. Initial Lab Findings in DKA Glucose475 Sodium132 Potassium4.8 Bicarbonate<10 BUN25 Acetoacetate4.8 B-hydroxybutyrate13.7 Free Fatty acids 2.1 Lactate4.6 Osmolarity310

13. Treatment of DKA  Replacement of fluid and electrolytes  Insulin therapy  Glucose administration

14. Replacement of Fluid and Electrolytes  Restores perfusion of tissues to normal and lowers levels of counterregulatory hormones  Average fluid deficit is 3-5 liters  1-2 liters of normal saline administered rapidly in the first 2 hours  If hypernatremia develops 1/2 NS can be substituted  Hyperkalemia usually present on admission recedes when insulin action begins; potassium replacement is then required  Phosphate deficit becomes apparent after insulin administration but is usually clinically silent  Bicarbonate is usually not given unless pH is below 7 or bicarb less than 5 mmol/l

15. Insulin Therapy  IV bolus of 10-20 units regular insulin  Follow by hourly insulin infusion  Insulin should be given intravenously until the urine is free of ketones

16. Glucose Administration  Once insulin has restored glucose uptake and suppressed hyperglucagonemia, hypoglycemia will occur unless exogenous glucose is provided  Glucose levels always fall before ketone levels decrease therefore exogenous glucose must be provided to cover the insulin needed to reverse ketosis  Glucose is usually started when plasma glucose reaches 250-300 mg/dl

17. Insulin-Glucose Infusion for DKA Blood glucose Insulin infusion D5W infusion <70 0.5 units per hour 150 cc/hour 70-1001.0125 101-1502.0100 151-2003.0100 201-2504.075 251-3006.050 301-3508.00 351-40010.00 401-45012.00 451-50015.00 >50020.00

18. Following Resolution of DKA  Most patients require 0.5-0.6 units of insulin per kg body weight  1/2 - 2/3 requirement is given as long-acting insulin - NPH, Lente, Ultralente or Lantus  1/3-1/2 is given as short-acting meal time insulin - regular, Humalog or Novolog  Give both long and short acting insulin subcutaneously about 2 hours prior to tapering insulin infusion  Patient education key to avoiding future episodes

19. Clinical Errors  Administration of hypertonic glucose solutions at the outset  Giving insulin in patients with severe volume deficit without sufficient fluids can cause fluid shift into cells can precipitate shock  Premature administration of potassium before insulin has begun to act can cause fatal hyperkalemia  Failure to administer potassium after insulin has begun to act can lead to fatal hypokalemia  Recurrent ketoacidosis caused by failure to maintain IV insulin and glucose until ketones have cleared or by failure to administer subcutaneous insulin before stopping IV infusion  Hypoglycemia caused by insufficient glucose administration

20. DKA and Pregnancy  Pregnancy is a state of relative insulin resistance marked by enhanced lipolysis and ketogenesis  High serum ketones may be teratogenic  DKA represents a substantial risk for the fetal compromise

21. Complications of DKA  Death is usually due to precipitating or complicating illness such as MI, pancreatitis or sepsis  Infection  Vascular thrombosis  Cerebral edema  Respiratory distress syndrome

22. Hyperosmolar Nonketotic Coma  Extreme hyperglycemia and dehydration which results when the ability to excrete glucose as rapidly as it enters the extracellular space  Maximum hepatic glucose output results in a plateau of plasma glucose no higher than 300-500 mg/dl  When sum of glucose excretion plus metabolism is less than the rate at which glucose enters extracellular space

23. Hyperosmolar Nonketotic Coma  Older patients with intercurrent illness with impaired ability to ingest fluids  When urine volume falls the ability to excrete glucose falls  As glucose rises CNS dysfunction occurs and water intake is additionally impaired  The result is extreme hyperglycemia and hyperosmolarity with high mortality  Either enough insulin is present to prevent ketosis or the extreme hyperglycemia inhibits lipolysis

24. Admission Findings: Hyperosmolar Nonketotic Coma  Extreme dehydration  Supine or orthostatic hypotension  Confusion to coma  Seizures or other neurological findings

25. Admission Findings: Hyperosmolar Nonketotic Coma  Average glucose 1200  Na 144  K 5  Bicarb 17  Osm 384

26. Treatment of HONK  Fluid repletion: give first 2-3 liters rapidly  Total deficit may be 10 liters: replete 1/2 the deficit in the first 6 hours  Insulin 10 unit bolus followed by sliding scale hourly  Treat underlying precipitating illness