Diabetic Ketoacidosis (DKA) Mona Omran, Jung Eun Lee, Tiffany Ou, Annie Yan PHM142 Fall 2015 Coordinator: Dr. Jeffrey Henderson Instructor: Dr. David Hampson

Introduction Life-threatening condition that arises when cells in the body are unable to get glucose they need for energy due to insufficient amount of insulin The body begins to break down fat and muscle for energy Ketones or fatty acids are produced They enter the bloodstream and make it more acidic

Causes Most susceptible people are those with Type 1 diabetes but it can happen with Type 2 diabetes Not enough food, having a severe infection or other illness, missed insulin treatment or becoming severely dehydrated

Symptoms Evidence of dehydration (dry mouth and decreased skin turgor) Often, a "ketotic" odour ( "fruity“) Nausea, vomiting, generalized weakness, confusion, abdominal tenderness and shortness of breath

Diagnosis Blood and urine tests for Ketone and glucose. The acceptable range for blood ketones is less than 0.6 mmol/L. If Blood glucose levels are consistently greater than 14 mmol/L for more than 1 day and blood ketones between 1.5 and 3.0 mmol/L. Decrease in the circulating blood volume, tachycardia and low blood pressure.

Hormonal Control of Blood Glucose Insulin Glycogen production Fat (Triglyceride) Production Glucagon Glycogen breakdown Amino Acid breakdown Fat breakdown

Ketone Body: Formation and Consequences 3 types of “Ketone Bodies” Good for periods of starvation… 3-HB Dehydrogenase Reduction Rxn Spontaneous Decarboxylation + H+

Ketone Body Metabolism during DKA

Treatment Resolving Dehydration: R ecommended 0.9% NaCl IV bolus to improve plasma osmolarity Insulin Therapy: E ncourage glucose uptake in peripheral tissues and decrease gluconeogensis and glycogenolysis

Treatment Electrolyte Therapy: K+ IV supplement required to avoid arrhythmias and cardiac arrest Bicarbonate therapy for severe ketoacidosis (pH<6.9) Phosphate therapy can be given (blood level < 10ml/dL) if phosphate and calcium levels are closely monitored

Prevention Type 1 Diabetes: No current, safe preventive measures Type 2 Diabetes: Lifestyle changes Lower calorie and fat intake Reduce sugar in diet Increase fibre intake Exercise -- recommended 150 minutes of ‘moderate’ or higher intensity of physical activity

Prevention Type 2 Diabetes: Drugs that can prevent the progression from pre-diabetes to diabetes: Metformin Decreases liver production of glucose (i.e. decreases conversion of glycogen to glucose) Reduces absorption of glucose at intestinal level (i.e. lowers amount of glucose to get into the body) Exact mechanism unknown

Prevention Early detection of onset of diabetic ketoacidosis through: Close and continuous monitoring of glucose levels and ketone levels through analysis of blood or urine Identifying at-risk individuals (by health care providers) Educating the patient Increasing awareness and knowledge in the community

Conclusion Diabetes Ketoacidosis is a potentially lethal complication of diabetes (both type 1 and 2) where there is: increased level of ketone bodies a drop in pH Variety of physiological effects Treatments are available but prevention would be best

Summary Slide Diabetic ketoacidosis is a serious complication of diabetes. It is characterized by evidence of high blood glucose and ketone levels. High glucagon:insulin ratio leads to accumulation of ketone bodies leading to several pathophysiology hyperglycemia, electrolyte imbalance, dehydration, and decrease in blood pH. The three main ketone bodies made are: acetoacetate, acetone, 3-Beta- Hydroxybutyrate. These are formed in liver mitochondria Treatment: Saline (NaCl) infusion, K+ infusion, insulin therapy Prevention: Lifestyle changes (eating healthier + exercise), metformin

References Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. (2013). Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Canadian Journal of Diabetes 2013, 37(suppl 1), S1-S212. Casteels, K., & Mathieu, C. (2003). Diabetic ketoacidosis. Reviews in Endocrine and Metabolic Disorders, 4(2), doi: /A: Gosmanov, A. R., Gosmanova, E. O., & Dillard-Cannon, E. (2014). Management of adult diabetic ketoacidosis. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 7, 255–264. Lebovitz, H. E. (1995). Diabetic ketoacidosis. The Lancet, 345(8952), Laffel, L. 'Ketone Bodies: A Review of Physiology, Pathophysiology and Application of Monitoring to Diabetes', Diabetes Metab Res Rev, 15 (1999), Rewers, A. (2010). Current controversies in treatment and prevention of diabetic ketoacidosis. Advances in Pediatrics,57(1), doi: /j.yapd Wolfsdorf et al. (2007). Diabetic ketoacidosis. Pediatric Diabetes, 8, doi: /j x