Diabetes Mellitus

Pediatric Critical Care Medicine

Emory University
Childrens Healthcare of Atlanta

Goals & Objectives

Understand the action of insulin on the
metabolism of carbohydrates, protein & fat
Understand the pathophysiology of IDDM & DKA
Understand the management approach to the
patient with DKA
Appreciate the complications that occur during
treatment

Classification
Type I (insulin-dependent diabetes mellitus, IDDM)

Severe lacking of insulin, dependent on exogenous insulin

DKA
Onset in childhood
?genetic disposition & is likely auto-immune-mediated

Type II (non-insulin-dependent diabetes mellitus,

NIDDM)

Not insulin dependent, no ketosis

Older patient (>40), high incidence of obesity
Insulin resistant
No genetic disposition
Increase incidence due to prevalence of childhood obesity

IDDM: Epidemiology
1.9/1000 among school-age children in the US;
12-15 new cases/100,00
Equal male to female
African-Americans: occurrence is 20-30%
compared to Caucasian-Americans
Peaks age 5-7 yrs and adolescence
Newly recognized cases: more in autumn & winter
Increase incidence in children with congenital
rubella syndrome
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Type I DM
15-70% of children with Type I DM present in DKA at
disease onset
1/350 of type I DM will experience DKA by age 18 yo
Risk of DKA increased by:
Very young children
Lower socioeconomic background
No family history of Type I DM

DKA:
Most frequent cause of death in Type I DM
One of the most common reasons for admission to PICU

IDDM: Etiology &

Pathophysiology
Diminished insulin secretion by destruction of

pancreatic islets cells via autoimmune process

80-90% of newly diagnosed cases have anti-islet
cell antibodies
More prevalent in persons with Addisons disease,
Hashimotos thyroiditis, pernicious anemia

Type I DM: Pathophysiology

Progressive destruction of -cells progressive
deficiency of insulin permanent low-insulin
catabolic state
Phases:
Early: defect in peripheral glucose predominates
Late: insulin deficiency becomes more severe

Decreased renal
blood flow and
glomerular
perfusion

Stimulates counter
regulatory hormone
release

Accelerated
production of
glucose and
ketoacids

Dehydrati
on

Increased lactic
acidosis

Type I DM: Pathophysiology

Hyperglycemia glucosuria (renal threshold 180
g/dL) osmotic diruresis: polyuria, urinary losses
of electrolytes, dehydration, & compensatory
polydipsia
Hyperglycemia hyperosmolality: cerebral
obtundation
{Serum Na+ + K+} x 2 + glucose/18 + BUN/3

Counter-regulatory hormones (glucagon,

catecholamines, cortisol) are released
Increased hepatic glucose production impairing
peripheral uptake of glucose
10

Type I DM: DKA

Lipid metabolism: increase lipolysis
Increased concentration of total lipids, cholesterone, TG,
free FA
Free FA shunted into ketone body formation; rate of
production>peripheral utilization & renal excretion
ketoacids
Ketoacidosis -hydroxybutyrate & acetoacetate
metabolic acidosis
Acetone (not contribute to the acidosis)

11

Type I DM: DKA

Electrolytes loss
Potassium: 3-5 mEq/kg
Phosphate: 0.5-1.5 mmol/kg
2,3-diphosphoglycerate: facilitates O2 release from HgB
Deficient in DKA, may contribute to formation of lactic
acidosis

Sodium: 5-10 mEq/kg

12

DKA: Presenting Features

13

Polyuria
Polydipsia
Polyphagia
Nocturia
Enuresis

Abdominal pain
Vomiting
Profound weight loss
Altered mental status
weakness

Type I DM: Clinical

Manifestations
Ketoacidosis is responsible for the initial
presentation in up to 25% of children
Early manifestations: vomiting, polyuria, dehydration
More severe: Kussmaul respirations, acetone odor on the
breath
Abdominal pain or rigidity may be present & mimic
acute abdomen
Cerebral obtundation & coma ultimately ensue

DKA exists when there is hyperglycemia (>300

mg/dL & usually <1,000 mg/dL); ketonemia,
acidosis, glucosuria & ketonuria
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DKA: Physical Exam

15

Tachycardia
Dry mucous membrane
Delayed capillary refill
Poor skin turgor
Hypotension
Kussmaul breathing

DKA: Physical Exam

Dehydration
Hyperosmolar: translocation of intracellular water to
extracellualr comparment
A rough estimation of how dehydrated the patient is to
facilitate proper rehydration
Studies have shown that clinical approximations often
are poor

16

DKA: Laboratory

17

Blood glucose
Urinary/plasma ketones
Serum electrolytes
BUN/Cr
Osmolarity
CBC, blood cx (if infection is suspected)
Blood gas

DKA: Laboratory Findings

Elevated blood glucose (usually <1,000)
Low bicarbonate level
Anion gap metabolic acidosis
Unmeasured ketoacids
Urine dipsticks measure acetoacetate: in DKA Bhydroxybutyrate to acetoacetate is 10:1
Helpful in determining if there is ketoacids in urine but
not sererity of DKA or response to treatment

18

DKA: Laboratory Findings

Sodium: low
Osmotic flux of water into extracellular space reduces
serum sodium concentration
Actual sodium: 1.6mEq/L per 100mg/dL rise in glucose
over 100
Hypertriglyceridemia low sodium
pseudohyponatremia

Potassium:
Level varies depending on urinary loss and severity of
acidosis
Potassium moves extracellularly in exchange for
hydrogen ions typical hyperkalemia on presentaion
Total body stores are depleted due to urinary loss
19

DKA: Laboratory Findings

Phosphate
Depleted in the setting of DKA
Serum level may not accurately represent total body
stores

20

DKA: Management
Goals: correction of

21

Dehydration
Acidosis
Electrolytes deficits
Hyperglycemia

DKA: Management
Fluids:
Avoid impending shock
Fluid replacement >4L/m2/24 hrs has been associate with
cerebral edema

Usually necessary to help expand vascular compartment

Fluid deficit should gradually be corrected over 36-48 hrs

Rehydration fluids should contain at least 115-135

mEq/L of NaCl
Start with NS and switch to NS if neccessary

22

DKA: Management
Postassium:
Total body depletion will become more prominent with
correction of acidosis
Continuous EKG monitoring is standard of care
30-40 mEq/L: in either KCl or KPhos

23

DKA: Management
Phosphate:
Total body depletion will become more prominent with
correction of acidosis
Hypophosphatemia may cause rhabdomyolysis,
hemolysis, impaired oxygen delivery
Calcium should be monitored during replacement

24

DKA: Management
Insulin should be initiated immediately
Insulin drips 0.1 U/kg/hr (NO BOLUS)
Gradual correction reducing serum glucose by 50-100
mg/dL/hr
Serum glucose often falls after fluid bolus: increase in
glomerular filtration with increased renal perfusion

25

DKA: Management
Dextrose should be added to IVF when serum
glucose <300
Blood glucose levels often correct prior to ketoacidosis
Should not lower insulin infusion unless: rapid correction
of serum glucose or profound hypoglycemia

26

DKA: Management
Bicarbonate is almost never administered
Bicarb administration leads to increased cerebral
acidosis:
HCO3- + H+ dissociated to CO2 and H2O
Bicarbonate passes the BBB slowly
CO2 diffuses freely exacerbating cerebral acidosis &
depression

Indications for bicarbonate use: only in severe

acidosis leading to cardiorespiratory compromise

27

DKA: Complication,
Cerebral Edema
Cerebral edema: 0.5-1% of pediatric DKA
Mortality rate of 20%
Responsible for 50-60% of diabetes deaths in children
Permanent neurologic disability rate of 25%

Typically develops within the first 24 hrs of

treatment
Etiology is still unclear
Signs & symptoms:

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Headache
Confusion
Slurred speech
Bradycardia
Hypertension

DKA: Complication,
Cerebral Edema
Theories of cerebral edema
Rapid decline in serum osmolality
This leads to the recommendation of limiting the rate of
fluid administration

Edema due to cerebral hypoperfusion or hypoxia

Activation of ion transporters in the brain
Direct effects of ketoacidosis and/or cytokines on
endothelial function

29

DKA: Cerebral Edema, risk

factors
Younger age
Increase in BUN
New onset
Longer duration of
symptoms
Lower PCO2
Severe acidosis

30

Use of bicarbonate
Large volumes of
rehydration fluids
Failure of correction of
Na with treatment

DKA: Cerebral Edema,

treatment
Lower intracranial pressure
Mannitol or 3% saline

Imaging to rule out other pathologies

Hyperventilation & surgical decompression are
less successful at preventing neurologic morbidity
& mortality

31

DKA: Complications
Thrombosis (esp with
CVL)
Cardiac arrhythmias
Pulmonary edema
Renal failure
Pancreatitis

32

Rhabdomyolysis
Infection
Aspiration pneumonia
Sepsis
Mucormycosis

Hyperglycemia
Hyperosmolar Syndrome

33

Pathophysiology
Insulin levels are sufficient to suppress lipolysis
and ketogenesis
Insulin levels are inadequate to promote normal
anabolic function & inhibit gluconeogeneis &
glycogenolysis
Cell deprivation triggers counter-regulatory surge,
increasing glucose via enhanced hepatic glucose
generation & insulin resistance

34

Pathophysiology
Hyperglycemia heightened inflammatory state
exacerbating glucose dysregulation
Osmotic diuresis dehydration decreased GFR
further glucose elevation

35

Pathophysiology
Morbidity & mortality associated with acute
hyperglycemia
Vascular injury
Thrombus formation
Disrupts the phagocytotic & oxidative burst functions of
the immune systemt
Disrupts BBB
Disrupts metabolism of the CNS worsens the effects of
ischemia on brain tissue

36

Pathophysiology
Dehydration is a major component
15-20% volume depleted
5-10% in DKA

Greater electrolyte loss due to massive osmotic

diuresis

37

Clinical Presentation
Similar to DKA

Polyuria
Polydipsia
Weight loss
Neurologic impairment

Different from DKA

Kussmaul breathing
Acetone breath
Abdominal discomfort, nausea & vomiting are less
severe

38

Laboratory Findings

Glucose: >600 mg/dL

HCO3>15
Serum osmolarity >320 mOsml/L
pH>7.3 without evidence of significant ketosis
Level of acidemia is influenced by severity of shock &
starvation

Lab values consistent with acute renal failure,

rhabodmyolysis & pancreatitis

39

Treatment
Insulin plays a secondary role
Hyperglycemia can often be corrected via volume
resuscitation
Renal perfusion is improved, GF is enhanced
Insulin gtt 0.1 U/kg/hr

40

Complications
Cardiac arrest
Refractory
arrhythmias
Pulmonary
thromboemboli
Circulatory collapse
Refractory shock

41

Acute renal failure

Rhabdomyolysis
Neurologic deficits
Electrolyte
disturbances
Multisystem organ
failure

Treatment
Adult mortality: 15%
Pediatric prevalence of HHS is unknown

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DKA

DKA

DKA

HHS

Mild

Moderate

Severe

Plasma glucose
mg/dL

>250

>250

>250

>600

Arteial pH

7.25-7.3

7.0-7.24

<7.0

>7.3

Serum bicarb
mEq/L

15-18

10 to <15

<10

>18

Urine ketones

Positive

Positive

Positive

Small

Serum ketones

Positive

Positive

Positive

Small

Effective sOsmo
mOsm/kg

variable

variable

Variable

>320

Anion gap

>10

>12

>12

Variable

AMS

Alerg

Alert/drowsy

Stupor/coma

Stupor/coma

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DKA

HHS

Total water(L)

Water (ml/kg)

100

100-200

Na+ (mEq/kg)

7-10

5-13

CL- (mEq/kg)

3-5

5-15

K+ (mEq/kg)

3-5

4-6

PO42- (mmol/kg)

5-7

3-7

Mg2+ (mEq/kg)

1-2

1-2

Ca2+(mEq/kg)

1-2

1-2

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