Diabetic Ketoacidosis and Hyperglycemia Valerie Robinson, D.O.

Hyperglycemia Type 1 DM, Type 2 DM, Gestational Diabetes May present with polyuria, polydipsia, weight loss May present with DKA Type 1: usually in children with rapid onset. Caused by autoimmune pancreatic ß-cell destruction, or idiopathic Type 2: usually in adults with insidious onset. Caused by insulin resistance, insulin secretory defect Genetic and environmental factors influence development of hyperglycemia. The main goals of treatment are to alleviate symptoms, minimize the development of long-term complications, enhance the patient's quality of life, and reduce the risk of death.

Complications of Hyperglycemia May lead to DKA, and Hyperosmolar Hyperglycemic State. Macrovascular disease  CAD, MI, CVA, PAD Diabetic foot ulcers Microvascular disease  nephropathy, retinopathy, neuropathy, Charcot’s foot, ED Increased risk of infxns and decreased healing Gestational  preeclampsia, SAB, premature labor, polyhydramnios, macrosomia, RDS

What is DKA? Severe electrolyte imbalance with dehydration Severe insulin shortage Usually occurs in type 1 but may also occur in type 2 May be the initial presentation of diabetes mellitus May be brought on by an infection or another precipitating factor trauma, CVD, pancreatitis, drugs, ETOH, poor diet

Signs and Symptoms Fruity odor to breath (exhaled acetone) Shock Abdominal pain (ileus or delayed emptying) Altered consciousness Nausea/Vomiting Dehydration Polyuria Polydipsia Kussmaul breathing (compensatory hyperventilation)

Pathogenesis Pancreatic islet cells are destroyed, resulting in a lack of insulin and hyperglycemia. Hyperglycemia induces profound osmotic diuresis, causing water and electrolyte loss, especially potassium. The body cannot properly use extracellular glucose, so starts producing ketones as an alternate energy source. Ketosis causes metabolic acidosis. Metabolic acidosis forces hydrogen ions into cells, displacing potassium ions that are lost through urine and vomiting. Increased anion gap: Usu. >20meq/L

Pathogenesis cont. Total-body potassium depletion is present, but serum potassium levels may be normal or high because of electrolyte shift Extreme fluid loss results in clinical shock In some cases, hyperglycemia and dehydration predominate, and acidosis is minimal

Tests Results When you suspect DKA, order the following: FSBS/serum glucose - Used serially to follow tx progress Urine or serum ketones ABG BMP K+ must be monitored closely BUN/Cr used to follow tx progress CBC Blood cultures >250 mg/dL rarely >800 mg/dL High levels confirm dx pH <7.3 pCO2 <40 mmHg - confirms dx, reveals severity K+ may be high or normal - K+ may fall rapidly in tx - BUN/Cr reveal dehydration Leukocytosis Possible sepsis

Tests cont. Results cont. Serum Phosphate, Ca, Mg Amylase/lipase LFTs You may choose to order the following Serum Phosphate, Ca, Mg Amylase/lipase LFTs Do if c/o abdominal pain EKG CXR Lipids May be decreased. - May decrease during tx May be elevated in DKA - May indicate pancreatitis Not usually elevated in DKA Look for peaked T or U waves - Look for evidence of precipitating event Look for precipitating event Likely elevated – aid in ketogenesis

Diagnosis pH <7.3 Hyperglycemia Ketonuria Dehydration Patient may be asymptomatic, but should still be treated before symptoms occur.

Treatment #1: HYDRATION Hydration with NS. Calculate fluid deficit. Assume 5-10% dehydration if patient is acidotic. Correct over 36-48 hours. Usually 500-1000mL bolus in first hour Children 10-20mL/kg bolus. May use NS, crystalloid, or LR

Treatment #2: Insulin Bolus of 0.1 Units/kg IV Then 0.1 Units/kg/hour IV Children: no insulin bolus. 0.05-0.1 Units/kg/hour IV OR (in mild DKA or long transport) Short-acting insulin Initial dose 0.3 Units/kg SQ Then 0.1 Units/kg/hour SQ until glucose <250 mg/dL Then 0.05 Units/kg/hour SQ until DKA is resolved Children: no insulin bolus. 0.15 Units/kg/2hours SQ or IM Caution: Do not reduce serum glucose by more than 80 mg/dL/hour in children, 80-100 mg/dL/hour in adults

Treatment #3: Potassium 20-40 meq/L added to the IV NS Titrated to serum K+ concentrations Usually added after assured of urine output

Other Treatment Bicarbonate may worsen hypokalemia and intracellular acidosis and cause cerebral edema. Used in ICU when pH <6.9 Sodium phosphate is not used routinely. Tx if: <1 mg/dL OR significant cardiac or respiratory compromise. Dextrose 5% if glucose falls too rapidly and when it falls <250mg/dL. Don’t stop insulin until acidosis is corrected. Caution: If you fail to monitor and replace electrolytes, rehydrate too fast, or reduce glucose too fast, you may cause cerebral edema. If + cerebral edema, do not replace more than 75% of fluid deficit May use mannitol 0.5-1.0 g/kg over 20 minutes

Follow-up Look for a cause of the DKA Make sure glucose is well-controlled at home and patient is educated regarding DKA.

Non-Ketotic Hyperosmolar Coma Hyperosmolar Hyperglycemic State Level of consciousness is depressed when plasma osmolality is high May be precipitated by concomitant use of certain quinolone antibiotics in patients with diabetes taking certain oral hypoglycemic agents Markedly elevated plasma osmolality Severe hyperglycemia >600 mg/dL, may exceed 1000 mg/dL No significant ketonuria/ketonemia No significant acidosis, pH >7.3 and bicarbonate >15meq/L Usually occurs in elderly patients who often have undiagnosed DM2 Thromboembolic complications are common Insulin requirement is less than that for DKA Requires ICU monitoring

References David Toth MD et al. Gestational Diabetes. First Consult . 29 January 2010 Dennis Saver MD et al. Diabetic Ketoacidosis. First Consult. 27 April 2010. Abbas E. Kitabchi MD, PhD et al. Clinical features and diagnosis of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults. UpToDate. 25 June 2012.