Antoinette Moran MD

Professor of Pediatrics
University of Minnesota
What Is Diabetes?

• The body does not make enough insulin (insulin deficiency).

And / Or

• Insulin does not work well enough in the body (insulin

resistance).
What is Diabetes?
A Mismatch of Insulin Supply and Demand

Normal Type 1 Pre-type 2 Type 2

Insulin Production Capacity, Secretion, Requirement

Test Criteria*

Fasting plasma glucose ≥ 7.0 mmol/L (126 mg/dl) on ≥2 occasions

or
≥ 11.0 mmol/L (200 mg/dl)
Casual glucose on ≥2 occasions or once with symptoms

or
HbA1c ≥ 6.5 % on ≥2 occasions

*Criteria the same for all types of diabetes

Most Pediatric Diabetes is Type 1

0-9 years, 0.79 per 1000 10-19 years, 2.80 per 1000
T1D: It Starts with Genetic Susceptibility
Polymorphisms of class II HLA genes encoding DQ and DR account for ~50% of the familial
aggregation of T1D (DR3 and DR4, DQ8).
Faulty recognition of “self”
People with T1D are at risk for other autoimmune diseases (thyroid, and celiac most common in
kids, also adrenal, vitiligo, alopecia, etc)
 Definition of DKA
• Diabetic
• Hyperglycemia (BG > 11.1 mmol/L, may be less with
starvation or in very young children)

• Keto
• Positive ketones (beta-hydroxybutyrate)

• Acidosis
• Venous pH < 7.25 / Arterial pH < 7.3
• and/or bicarbonate < 15 mmol/L
Why does DKA occur ?

1) FAILURE TO TAKE INSULIN Insulin deficiency

2) Vomiting / poor sick day

management Too much counter-
3) Infection regulatory hormone
4) Stress (relative insulin deficiency)
 Disturbances in Physiology
Insulin deficiency leads to:

• Hyperglycemia
• Ketogenesis
• Dehydration
• Total body potassium depletion
• Total body sodium depletion
• Total body phosphorus depletion
• Alterations in mental status
 Hyperglycemia in DKA
• Absence of insulin to promote use of glucose as energy source
leads to perceived fasting state (tissues are starving)
• Release of counterregulatory hormones
• Gluconeogenesis, glycogenolysis→ ↑hepatic glucose production
• Muscle catabolism to fuel gluconeogenesis
• ↑free fatty acids →ketones →acidosis
 Disturbances in Physiology
Insulin deficiency leads to:
• Hyperglycemia
• Ketogenesis
• Dehydration
• Total body potassium depletion
• Total body sodium depletion
• Total body phosphorus depletion
• Alterations in mental status
 Consequences of Ketogenesis
Acidosis
• Kussmaul respirations
• Promotes shift of K+ from intracellular to extracellular space
• Ultimately organ failure, decreased respiratory drive and death

Dehydration
• Ketones cause nausea  vomiting and
further dehydration (on top of
glycosuria)
• Worsening osmotic diuresis (ketone
excretion pulls Na+ and K+ out in urine)
• Shock, death
 Disturbances in Physiology
Insulin deficiency leads to:

• Hyperglycemia
• Ketogenesis
• Dehydration
• Total body potassium depletion
• Total body sodium depletion
• Total body phosphorus depletion
• Alterations in mental status
 Dehydration
• Most patients at least 10% dehydrated
₋ Dehydration usually appears less severe
because they are hyperosmolar
• As intravascular volume decreases, GFR
decreases, and hyperglycemia worsens
₋ Well-perfused kidneys can usually keep
glucose less than ~28 mmol/L
 Disturbances in Physiology
Insulin deficiency leads to:
• Hyperglycemia
• Ketogenesis
• Dehydration
• Total body potassium depletion
• Total body sodium depletion
• Total body phosphorus depletion
• Alterations in mental status
Potassium Depletion in DKA
• Urinary loss of potassium → total body K depletion
• Acidosis shifts intracellular potassium to extracellular space---
boosts intravascular potassium concentration creating a false
sense of K normalcy
• Treatment of DKA with resolution of acidosis moves potassium
back into intracellular space

Serum potassium at presentation may be

•Normal: drops with treatment

Potassium Depletion in DKA
• Urinary loss of potassium → total body K depletion
• Acidosis shifts intracellular potassium to extracellular space---
boosts intravascular potassium concentration creating a false
sense of K normalcy
• Treatment of DKA with resolution of acidosis moves potassium
back into intracellular space

Serum potassium at presentation may be

• Low: may become dangerously low during treatment
• Normal: drops with treatment
Potassium Depletion in DKA
• Urinary loss of potassium → total body K depletion
• Acidosis shifts intracellular potassium to extracellular space---
boosts intravascular potassium concentration creating a false
sense of K normalcy
• Treatment of DKA with resolution of acidosis moves potassium
back into intracellular space

Serum potassium at presentation may be

• Low: may become dangerously low during treatment
• Normal: drops with treatment
• High: indicates poor renal perfusion---wait before replacing
 Disturbances in Physiology
Insulin deficiency leads to:

• Hyperglycemia
• Ketogenesis
• Dehydration
• Total body potassium depletion
• Total body sodium depletion
• Total body phosphorus depletion
• Alterations in mental status
 Cerebral Edema
• It is a consequence of
treatment
• Because of the blood brain
barrier, shifts of brain glucose
and osmolality are much
slower than peripheral shifts.
• This can lead to increased
osmolality in the brain which
can produce cerebral edema
When does Cerebral Edema Occur?

7 Number of Children
Number with Neurologic Deterioration

0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 25

Hours after Therapy Started

Adapted from Glaser, et.al, NEJM, 2001
 Signs and Symptoms of Cerebral Edema
• Sudden and severe headache
• Combativeness, disorientation, agitation, change in mental status,
posturing, seizure
• Pupil changes (asymmetry, sluggish), papilledema
• Change in vital signs
• bradycardia, hypertension

• gasping/irregular respirations
• apnea

• hypothermia
Who Gets Cerebral Edema in DKA?
• Infants and children <5 years
₋ 95% of cases are under 2 years old
• Initial presentation of T1D (usually sicker because no one knows they
have diabetes)
• Higher sodium levels at presentation
• Severe acidosis
• Elevated BUN
• Patient got bicarbonate (sicker??)
• Excess or hypotonic fluids +/-
 Why is Cerebral Edema More Common in the
Very Young?
• Delayed diagnosis

• More quickly dehydrated

• Less mature blood-brain barrier

 DKA: Clinical Picture

1. History of polydipsia, polyuria,

weight loss, vomiting
2. Dehydration: dry mucous membranes,
tachycardia, LATE: poor perfusion, hypotension
• Look less dehydrated than they really are
(hyperosmolar dehydration)
3. “Fruity” smell to breath (acetone)
4. Kussmaul respirations (metabolic acidosis)
5. Abdominal pain (can mimic surgical abdomen)
DKA: Clues to Diagnosis

• “Gastro-enteritis” ---vomiting, but no diarrhea

• Dehydration, but excessive urine output !
• “Respiratory distress”, but no lung findings

History and PE =
95% of diagnosis

Take the history,

Listen to the history
 Complications of DKA

• Hypoglycemia
• Persistent ketoacidosis
₋ inadequate fluids
₋ inadequate insulin
• Infection (mucormycosis)
• CEREBRAL EDEMA
• Other intracranial complications (thrombosis)
• Shock, DEATH
 DKA Treatment Goals
1. Restore fluid volume

2. Inhibit ketogenesis with insulin

3. Replace body salts

4. Correct acidosis
(self-corrects with treatment)

5. Correct hyperglycemia
 Therapy Guidelines: Fluids
• The most important step!

• Initial repletion of intravascular space

₋ 10-15 cc/kg NS or LR, repeat if needed

• Replacement:
₋ maintenance + deficit over 36-48 hrs
₋ figure ≥10% dehydrated)
₋ usually ~1.5x maintenance

• Replacement fluid composition

₋ ½ or ¾ NS
₋ Add dextrose when glucose < 20 mmol
₋ Potassium 20-60 meq/L depending on access, laboratory availability and
potassium status

• If no iv access and patient vomiting, consider rectal or intraosseous fluids until

you can get access or transfer patient to a major center
 Therapy Guidelines Potassium
• Patients are total body K depleted (caution: blood levels may be
transiently high if they are so dehydrated that there is no urine output)
• If you can’t measure serum K, follow the ECG, give as much K+ as you
safely can intravenously
• Later encourage high K diet

ECG Changes in Hypokalemia

 Therapy Guidelines: Insulin
• Standard in US: iv insulin drip starting at 0.1 units/kg/hour (half that much for a
child age <6 years)

₋ Biggest advantage is ability to make very rapid changes

₋ Must be able to check glucose levels at least every 2 hours and have an accurate
infusion pump
• If not available, subcutaneous (or if really dehydrated IM) insulin
 0.1 units/kg regular (“soluble”) insulin every 1-2 hours
 Once patient is well perfused, can switch to subcutaneous insulin every 4 hours
• Aim for a glucose drop of about 5.0 mmol/L/hr, slower if unable to regularly
monitor glucose and/or potassium
 But initial glucose drop will be greater just from hydration—down to about 28
mmol/L

• Don’t stop giving regular (soluble) insulin until ketones have cleared and/or acidosis
is resolved (clinically well)
 Therapy Guidelines: Mental Status Monitoring

1. Diligent monitoring of vital signs and neurologic status

• 50% cases of neurologic complications had identifiable
warning sign at least 1 hour before collapse
2. No excessive fluid administration over first 12 hours unless
clinically indicated
3. Have mannitol available and administer
at first signs of cerebral edema
• Most effective within 5-10 minutes
of signs of clinical deterioration
4. Identify those at greatest risk
 Prevention of DKA
• Provider education
₋ Recognize potential new diabetes DKA
₋ How to treat an ill, ketotic patient with diabetes to prevent
acidosis

• Public and patient education

₋ Recognize potential new
diabetes and DKA---everyone
who cares for children should
know symptoms
₋ Sick day management
(including communication with
health care team)
• Access to insulin
Case
• 22 yo male with 6 yr history T1D, followed at Mulago Hospital Pediatric Diabetes Clinic
• 1 week prior to presentation was diagnosed and treated for UTI
• Presented with 1 day history of vomiting, abdominal pain, ?fever, headache
─ No diarrhea
─ No mental status changes
• Vitals: temp 35.3, BP 131/70, pulse 128; Glucose 20
• Exam---hyperactive precordium, ? Tricuspid murmur, other systems unremarkable
Admitted. Diagnoses---
1. Patient with type 1 diabetes
2. Gastritis
3. R/O Malaria
4. R/O UTI
 Nov 29 Nov 30 Dec 1 Dec 2
Clinical Vomiting, abd pain Still vomiting, ? Vomiting, appears ill
“gastritis” “resp distress”- and dehydrated—
add O2 DKA
Vitals BP 110/60, P-87; BP ? ? BP 140’s/90’s, P 180-
137/64, P80, RR22 230
Glucose 22 ? ? 23, 28
Labs *result 2d later: WBC ?
11.3 (84% neut), Hgb
13.3, K- 5.45 (3.7-5.4),
Na 135, LFTs OK
Fluids 2LNS, 1L LR over 24h ? ? 2L LR
Insulin Soluble 51 units IV ? ? Start Mixtard 30U
am, 20 U pm
Other Antibiotics, Continue with ?
Meds ondansetron, same
morphine
Later Glu 10, “sepsis”, abd Cardiac arrest, death
US