Diabetes is a condition where the body does not properly process glucose due to lack of insulin or insulin resistance. Diabetic ketoacidosis (DKA) occurs when a lack of insulin causes the body to break down fat and produce ketones, leading to hyperglycemia, ketosis and acidosis. DKA treatment involves rehydration, insulin therapy to lower blood glucose and ketone levels, electrolyte replacement, and identifying/treating the precipitating cause. Complications can include infection, shock, cerebral edema and death if not properly managed. Prevention relies on education about sick day management to avoid DKA during illness.

3. UNDERSTANDING DIABETES
Diabetes mellitus, often referred to simply as
DIABETES.
Diabetes is a condition in which the body:
• Does not produce enough insulin, and/or
• Does not properly respond to insulin
Insulin is a hormone produced in the pancreas. Insulin enables cells to
absorb glucose in order to turn it into energy.
3

4. Type 1 vs. Type 2
Type 1 diabetes Type 2 diabetes
Diagnosed in children
and young adults
Typically diagnosed in
adulthood
Previously known as
Juvenile Diabetes
Also found in overweight
children
Insulin-dependent Non-insulin-dependent
Body does not produce
insulin
Body fails to produce
and properly use insulin

6. Complications of blood glucose alterations
• Hypoglycemia
• Hyperglycemia
• Ketosis
• Acidosis
• DKA (Hyperglycemia + Ketosis + Acidosis)
Blood Glucose Alterations
Normal fasting blood glucose level 4-6 mmol/L

8. DIABETIC KETOACIDOSIS (DKA)
Hyperosmolar Hyperglycemic State (HHS)

9. DIABETIC KETOACIDOSIS (DKA)
• A state of absolute or relative insulin deficiency
aggravated by ensuing hyperglycemia, dehydration,
and acidosis-producing derangements in intermediary
metabolism, including production of serum acetone.
• Can occur in both Type I Diabetes and Type II
Diabetes
– In type II diabetics with insulin
deficiency/dependence
• The presenting symptom for ~ 25% of Type I
Diabetics.

11. Diabetic KetoAcidosis (DKA)
1. 160,000 Admissions to private
hospitals/year
2. Cost = over 1 billion $ annually
3. 65% = <19 years old
4. Main cause of death in children with
diabetes (approximately 85%)
5. Cerebral edema in 69%

12. Hyperosmolar Hyperglycemic State (HHS)
• An acute metabolic complication of diabetes
mellitus characterized by impaired mental status
and elevated plasma osmolality in a patient with
hyperglycemia.
• Occurs predominately in Type II Diabetics
– A few reports of cases in type I diabetics.
• The presenting symptom for 30-40% of Type II
diabetics.
• Not commonly associated with ketonaemia and
acidosis

14. The biochemical criteria for the diagnosis of DKA3,4
• Hyperglycemia - blood glucose greater than 11.1 mmol/L
• Ketosis - ketones present in blood and/or urine
• Acidosis - pH less than 7.3 and/or
bicarbonate less than 15 mmol/L
Classic Triad of DKA

15. DKA is generally categorized by the severity of the
acidosis.
• MILD – Venous pH less than 7.3 and/or
bicarbonate concentration less than 15 mmol/L
• MODERATE – Venous pH less than 7.2 and/or
bicarbonate concentration less than 10 mmol/L
• SEVERE – Venous pH less than 7.1 and/or
bicarbonate concentration less than 5 mmol/L
CLASSIFICATION OF DKA

17. Risk factors for DKA at onset
• Age <12 yrs
• No first degree diabetic relative
• Lower socioeconomic status
• High dose glucocorticoids, atypical antipsychotics, diazoxide
and some immunosuppresive drugs
• Poor access to medical care
• Uninsured
• Usage of SGLT-2 inhibitor – euglycaemic DKA
SGLT2 inhibitors blunt insulin production in the face of stress
hormones leading to increased ketotic metabolism

19. Why do ketones develop?
No carbohydrate intake
• fasting
• gastroenteritis
• Atkins diet, neonates fed high-fat milk
Prolonged exercise, pregnancy
Lack of insulin activity
• onset of diabetes (insufficient secretion)
• interruption of insulin delivery in established pt
Increase in insulin resistance
• infection, illness, surgery, stress
Alcohol, salicylate ingestion, inborn metabolic errors

20. Causes of DKA/HHS
• Stressful precipitating event that results in increased
catecholamines, cortisol, glucagon.
– Infection (pneumonia, UTI)
– Alcohol, drugs
– Stroke
– Myocardial Infarction
– Pancreatitis
– Trauma
– Medications (steroids, thiazide diuretics)
– Non-compliance with insulin

22. PATHOPHYSIOLOGY OF DKA
Wolfsdorf J, Glaser N, Sperling MA; American Diabetes Association. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the
American Diabetes Association. Diabetes Care. 2006;29(5):1150-1159. Reprinted with permission from The American Diabetes Association.

23. PATHOPHYSIOLOGY OF DKA

26. DKA is a complex metabolic state of: hyperglycemia,
ketosis, and acidosis
Symptoms include:
– Deep, rapid breathing
– Fruity breath odor
– Very dry mouth
– Nausea and vomiting
– Lethargy/drowsiness
DKA is life-threatening and needs immediate treatment

27. Symptoms of DKA/HHS
• Polyuria
• Polydypsia
• Blurred vision
• Nausea/Vomiting
• Abdominal Pain
• Fatigue
• Confusion
• Obtundation

28. Physical Examination in DKA/HHS
• Hypotension, tachycardia
• Kussmaul breathing (deep, labored breaths)
• Fruity odor to breath (due to acetone)
• Dry mucus membranes
• Confusion
• Abdominal tenderness

30. Diagnostic Criteria for DKA and HHS
Mild DKA Moderate DKA Severe DKA HHS
Plasma glucose
mmol/L
> 14 > 14 > 14 > 33.3
Arterial pH 7.25-7.30 7.00-7.24 < 7.00 > 7.30
Sodium Bicarbonate
(mEq/L)
15 – 18 10 - <15 < 10 > 15
Urine Ketones Positive Positive Positive Small
Serum Ketones Positive Positive Positive Small
Serum Osmolality
(mOsm/kg)
Variable Variable Variable > 320
Anion Gap > 10 > 12 > 12 variable
Mental Status Alert Alert/Drowsy Stupor/Coma Stupor/Coma
Serum ketones positive if > 1mg/dl or < 0.1 mmol/L
Anion gap Na + K – Cl – Hco3 target < 10

33. Identify and Treat the Precipitating
Factor
• Insulin omission – MOST COMMON CAUSE of DKA
• New diagnosis of diabetes
• Infection / Sepsis
• Myocardial infarction
– Small rise in troponin may occur without overt
ischemia
– ECG changes may reflect hyperkalemia
• Thyrotoxicosis
• Drugs

34. Treatment of DKA
• Once resolved
– Convert to home insulin
regimen
– Prevent recurrence
• Initial hospital
management
– Replace fluid and
electrolytes
– IV Insulin therapy
– Glucose administration
– Watch for complications
– Disconnect insulin pump

35. Treatment of DKA
Fluids and Electrolytes
• Fluid replacement
–Restores perfusion of the tissues
•Lowers counterregulatory hormones
•Increase insulin sensitivity
–Average fluid deficit 3-5 liters

36. Initial fluid resuscitation
• 15 to 20 mL/kg lean body weight per hour
• (approximately 1000 mL/hour in an average-sized
person) for the first couple of hours
• Maximum of <50 mL/kg in the first four hours
• 1-2 liters of normal saline over the first 2 hours
• Slower rates of 500cc/hr x 4 hrs or 250 cc/hr x 4
hours-When fluid overload is a concern
• If hypernatremia develops ½ NS can be used

37. Treatment of DKA
Fluids and Electrolytes
• Hyperkalemia initially present
– Resolves quickly with insulin drip
– Once urine output is present and K<5.0, add 20-40
meq KCL per liter.
• Phosphate deficit
– May want to use Kphos
• Bicarbonate not given unless pH <7 or
bicarbonate <5 mmol/L

38. Treatment of DKA
Insulin Therapy
• IV bolus of 0.1-0.2 units/kg (~ 10 units) regular
insulin
• Follow with hourly regular insulin infusion
• Glucose levels
– Decrease 4 to 5.5 mmol/L per hour
– Minimize rapid fluid shifts

39. Treatment of DKA
Glucose Administration
• Supplemental glucose
– Hypoglycemia occurs
• Insulin has restored glucose uptake
• Suppressed glucagon
– Prevents rapid decline in plasma osmolality
• Rapid decrease in insulin could lead to cerebral edema
• Glucose decreases before ketone levels decrease
• Start glucose when plasma glucose < 16.6
mmol/L

40. Insulin-Glucose Infusion for DKA
Blood glucose Insulin Infusion D5W Infusion
<70 0.5 units/hr 150 cc/hr
70-100 1.0 125
101-150 2.0 100
151-200 3.0 100
201-250 4.0 75
251-300 6.0 50
301-350 8.0 0
351-400 10.0 0
401-450 12.0 0
451-500 15.0 0
>500 20.0 0

41. Treatment of HHS
• Hydration!!!
– Even more important than in DKA
• Find underlying cause and treat!
• Insulin drip
– Should be started only once aggressive hydration has
taken place.
– Switch to subcutaneous regimen once glucose <
11mmol/L and patient eating.
• Serial Electrolytes
– Potassium replacement.

42. Pottasium Replacement
• If the initial K is below 3.3 mmol/L,
IV potassium chloride (KCl; 20 to 40
mmol/hour, before insulin therapy till raise
the serum potassium concentration into the
normal range of 4 to 5 mmol/L
• 3.3 to 5.3 given iv K with insulin infusion
• If above 5.3 not to given iv K till level less than
than

43. Resolution of ketoacidosis in DKA
• ●Normalization of the serum anion gap (less
than 12 mEq/L) and blood beta-
hydroxybutyrate levels
• ●Patients with HHS are mentally alert and the
effective plasma osmolality has fallen below
315 mOsmol/kg
• ●The patient is able to eat

44. Caveat
• Urinary ketones by the nitroprusside method can
be used for the initial diagnosis of ketoacidosis
• It should not be used for monitoring resolution of
DKA.
• Nitroprusside reacts mainly with acetoacetate, to
a much lesser degree with acetone (which is not
an acid), and not with beta-hydroxybutyrate.
• A positive nitroprusside test may persist for up to
36 hours after resolution of the ketoacidosis due
to a positive reaction with acetone, which is
slowly eliminated,

45. Once DKA Resolved
Treatment
• Most patients require 0.5-0.6 units/kg/day
• Pubertal or highly insulin resistant patients
– 0.8-1.0 units/kg/day
• Long acting insulin
– 1/2-2/3 daily requirement
– NPH, Lente, Ultralente or Lantus
• Short acting insulin
– 1/3-1/2 given at meals
– Regular, Humalog, Novolog
• Give insulin at least 2 hours prior to weaning insulin
infusion.

46. Copyrights apply

48. Complications of DKA
• Infection
– Precipitates DKA
– Fever
– Leukocytosis can be secondary
to acidosis
• Shock
– If not improving with fluids
r/o MI
• Vascular thrombosis
– Severe dehydration
– Cerebral vessels
– Occurs hours to days after DKA
• Pulmonary Edema
– Result of aggressive fluid
resuscitation
• Cerebral Edema
– First 24 hours
– Mental status changes
– Tx: Mannitol
– May require intubation with
hyperventilation

50. Prevention of DKA / HHS
• Type 1 diabetes
– Education around sick day management
– Continuation of insulin even when not eating
– Frequent monitoring when ill
• Type 2 diabetes
– Education around sick day management
– Frequent monitoring when ill

51. Prevention of DKA
Sick Day Rules
• Never omit insulin
– Cut long acting in half
• Prevent dehydration
and hypoglycemia
• Monitor blood sugars
frequently
• Monitor for ketosis
• Provide supplemental
fast acting insulin
• Treat underlying
triggers
• Maintain contact with
medical team

54. Conclusion
• Successful management
requires
– Judicious use of fluids
• Establish good perfusion
– Insulin drip
• Steady decline
• Complete resolution of ketosis
– Electrolyte replacement
– Frequent neurological evaluations
– High suspicion for complications
• Determine etiology to avoid
recurrent episodes