1. Diabetes Mellitus Type 1

2. Epidemiology
Incidence – increase with age through puberty then declines
Prevalence – 1.2 to 1.9/1000
Geography – common in northern and southern areas of the world, such as Scandinavia and new Zealand

3. Underlying pathogenesis?
Insulin deficiency

4. Combination of genetics and environment
Causes?
Combination of genetics and environment

5. Genetic causes 30-50% concordant in identical twins
1/40-80 or 1/20-40 chance of developing diabetes if mom or dad has diabetes, respectively
HLA DR3 or DR 4
3.5-fold increase with either one
10-fold increase with both
95% of type 1 have both
Associated with other autoimmune diseases such Graves’ disease, hypothyroidism, alopecia

6. Environmental cause
Viral infection, such as parvovirus B19 and mumps, trigger islet cell destruction, which accounts for frequent occurrence of type 1 in spring and fall

7. Rare causes
Pancreatitis - not common in children except those with familial triglyceride
Defective beta cell genes

8. Clinical symptoms
Subacute or acute

9. Subacute presentations?
Malaise
Weight loss – breaking down of proteins and fats to produce energy for the cells, because glucose could not be transported into the cells without insulin
Polyuria
Polydipsia
Polyphagia
Noctural enuresis

10. Acute presentations? Associated with diabetic ketoacidosis
Nausea and vomiting
Abdominal pain due to DKA or appendicitis
Dehydration or shock from osmotic diuresis
Breathing
Fruity smell
Kussmaul’s breathing
Altered mental status

11. Tests for diagnosis of diabetes mellitus type 1?
Fasting plasma glucose  126 mg/dL on two occasions
Random plasma glucose  200 mg/dL with symptoms
Two hours glucose tolerance test with plasma glucose  200 mg/dL at 2 hour

12. Distinctions from diabetes mellitus type 2
Thin
Weight loss
Insulin:serum glucose
High in type 2
Low in type 1

13. Tests for work-up? Urinalysis Hemoglobin A1c Fasting lipid panel
Proteinuria – should get urine microalbumin
Glucose does not confirm or rule out diagnosis of diabetes mellitus
Ketones does not confirm or rule out diagnosis of DKA
Hemoglobin A1c
Fasting lipid panel

14. Diagnosis of DKA? Hyperglycemia Ketones – β-hydroxybutyrate
Metabolic acidosis

15. Work-up of DKA? Chemistry ABG Serum β-hydroxybutyrate Glucose Sodium
Potassium
Magnesium
Phosphorus
BUN and creatinine
ABG
Serum β-hydroxybutyrate
Sodium - – high from dehydration, low from dilutional hyperglycemia
Potassium – high because K+ moves into the cell, as bicarbonate moves out of the cell to compensate for the acidosis

16. Management Hydration Correct ketoacidosis Monitor electrolytes
Start insulin regimen

17. Hydration
Deficits
6-8 liters in DKA and 8-10 liters in NKH
5-10% in children
Rate of replacement depends on the severity of shock – ½ fluid deficit + 40% of maintenance + urine loss + other losses (mL/hour)
Start with normal saline solution and switch to ½ normal saline when patient is hemodynamically stable and potassium is added into IV fluid, because potassium is an osmotic solute
Add dextrose to IV fluid once serum glucose drops < 300 mg/dL to prevent rapid decrease in osmolality leading to cerebral edema

18. Correct ketoacidosis? Regular insulin bolus Insulin infusion
After IV fluid bolus to prevent precipitating drop in glucose
unit per kg
Insulin infusion
0.1 unit per kg/hour
Adjust insulin rate or IV fluid rate to maintain serum glucose mg/dL

19. Monitor electrolytes Glucose
Drop after hydration due to increased renal filtration and decreased insulin resistance due to decreased glucacon, corticoticoids, and catecholamines
Not to lower faster to than 100mg/dL per hour or below 200 – 250 mg/dL acutely because of the risk of cerebral edema
Potassium - drops very quickly after hydration
Potassium moves back into the cells due to insulin and decreased acidosis
0.1 change in pH = 0.6 mEq/L change in potassium in opposite direction
Replace as soon as patient has urine output and no more hyperkalemia
Magnesium and phosphorus – supplement as necessary

20. Monitor metabolic acidosis
Follow serum bicarbonate and anion gap
Not need to do serial ABG
Bicarbonate for acidosis
Not routine because CO2 moves into CSF and worsens cerebral pH
Indication
pH < 7.1 because of decreased cardiac contractility and vasodilation impairing tissue perfusion
Life-threatening kyperkalemia

21. Insulin
Start SQ regular insulin 1 hour or NPH 4 hours prior to stopping insulin infusion
Insulin regimen
Total 0.5 units/kg/day
2/3 in AM and 1/3 in PM
2/3 NPH and 1/3 regular in AM & 1/2 NPH and 1/2 regular in PM

22. The End