Diabetes Mellitus

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Diabetes Mellitus
Pediatric Critical Care Medicine Emory
University Childrens Healthcare of Atlanta
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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

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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 (gt40), high incidence of obesity
• Insulin resistant
• No genetic disposition
• Increase incidence due to prevalence of childhood
  obesity

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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

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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

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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

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Osmotic Diuresis
Decreased renal blood flow and glomerular
perfusion
Dehydration
Stimulates counter regulatory hormone release
Increased lactic acidosis
Accelerated production of glucose and ketoacids
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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

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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 productiongtperipheral utilization renal
  excretion ? ketoacids
• Ketoacidosis ? ?-hydroxybutyrate acetoacetate ?
  metabolic acidosis
• Acetone (not contribute to the acidosis)

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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

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DKA Presenting Features

• Polyuria
• Polydipsia
• Polyphagia
• Nocturia
• Enuresis

• Abdominal pain
• Vomiting
• Profound weight loss
• Altered mental status
• weakness

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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 (gt300
  mg/dL usually lt1,000 mg/dL) ketonemia,
  acidosis, glucosuria ketonuria

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DKA Physical Exam

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

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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

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DKA Laboratory

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

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DKA Laboratory Findings

• Elevated blood glucose (usually lt1,000)
• Low bicarbonate level
• Anion gap metabolic acidosis
• Unmeasured ketoacids
• Urine dipsticks measure acetoacetate in DKA
  B-hydroxybutyrate to acetoacetate is 101
• Helpful in determining if there is ketoacids in
  urine but not sererity of DKA or response to
  treatment

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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

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DKA Laboratory Findings

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

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DKA Management

• Goals correction of
• Dehydration
• Acidosis
• Electrolytes deficits
• Hyperglycemia

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DKA Management

• Fluids
• Avoid impending shock
• Fluid replacement gt4L/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 ½ NS if neccessary

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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

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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

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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

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DKA Management

• Dextrose should be added to IVF when serum
  glucose lt300
• Blood glucose levels often correct prior to
  ketoacidosis
• Should not lower insulin infusion unless rapid
  correction of serum glucose or profound
  hypoglycemia

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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

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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
• Headache
• Confusion
• Slurred speech
• Bradycardia
• Hypertension

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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

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DKA Cerebral Edema, risk factors

• Younger age
• New onset
• Longer duration of symptoms
• Lower PCO2
• Severe acidosis

• Increase in BUN
• Use of bicarbonate
• Large volumes of rehydration fluids
• Failure of correction of Na with treatment

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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

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DKA Complications

• Thrombosis (esp with CVL)
• Cardiac arrhythmias
• Pulmonary edema
• Renal failure
• Pancreatitis

• Rhabdomyolysis
• Infection
• Aspiration pneumonia
• Sepsis
• Mucormycosis

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Hyperglycemia Hyperosmolar Syndrome
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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

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Pathophysiology

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

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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

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Pathophysiology

• Dehydration is a major component
• 15-20 volume depleted
• 5-10 in DKA
• Greater electrolyte loss due to massive osmotic
  diuresis

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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

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Laboratory Findings

• Glucose gt600 mg/dL
• HCO3gt15
• Serum osmolarity gt320 mOsml/L
• pHgt7.3 without evidence of significant ketosis
• Level of acidemia is influenced by severity of
  shock starvation
• Lab values consistent with acute renal failure,
  rhabodmyolysis pancreatitis

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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

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Complications

• Cardiac arrest
• Refractory arrhythmias
• Pulmonary thromboemboli
• Circulatory collapse
• Refractory shock

• Acute renal failure
• Rhabdomyolysis
• Neurologic deficits
• Electrolyte disturbances
• Multisystem organ failure

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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 gt250 gt250 gt250 gt600
Arteial pH 7.25-7.3 7.0-7.24 lt7.0 gt7.3
Serum bicarb mEq/L 15-18 10 to lt15 lt10 gt18
Urine ketones Positive Positive Positive Small
Serum ketones Positive Positive Positive Small
Effective sOsmo mOsm/kg variable variable Variable gt320
Anion gap gt10 gt12 gt12 Variable
AMS Alerg Alert/drowsy Stupor/coma Stupor/coma
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DKA HHS
Total water(L) 6 9
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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