Type 1 Diabetes Mellitus

and Diabetic
Ketoacidosis
MBBS 3
 DEFINITION OF DKA

• Hyperglycemia – Blood glucose of >200 mg/dL (11 mmol/L)

AND

• Metabolic acidosis – Defined as a venous pH <7.3 or plasma

bicarbonate <15 mEq/L (15 mmol/L) AND

• Ketosis – Determined by the presence of ketones in the blood

or urine
 Functions of Insulin
Fasted
state ↓ Insulin Catabolic
Level state

Postprandia ↑ Insulin
Anabolic
l state Level
state
 Influence of High Insulin or Low
Insulin on Metabolic Processes
HIGH PLASMA INSULIN LOW PLASMA INSULIN (FASTED
(POSTPRANDIAL STATE) STATE)

LIVER Glucose uptake Glucose production

Glycogen synthesis Glycogenolysis
Lipogenesis Absence of lipogenesis
Absence of Gluconeogenesis
gluconeogenesis
Absence of ketogenesis Ketogenesis
 Influence of High Insulin or Low
Insulin on Metabolic Processes
HIGH PLASMA INSULIN (POSTPRANDIAL
LOW PLASMA INSULIN (FASTED STATE)
STATE)
MUSCLE
Glucose uptake Absence of glucose uptake

Glucose oxidation Fatty acid and ketone oxidation

Glycogen synthesis Glycogenolysis

Protein synthesis Proteolysis and amino acid release

 Influence of High Insulin or Low
Insulin on Metabolic Processes
HIGH PLASMA INSULIN LOW PLASMA INSULIN (FASTED
(POSTPRANDIAL STATE) STATE)
Adipose tissue Glucose uptake Absence of glucose uptake

Lipid synthesis Lipolysis and fatty acid release

Triglyceride uptake Absence of triglyceride uptake

 Effects of Insulinopaenia
Hyperglycemia Osmotic diuresis (>
180 mg/dL; 10 mmol/L)

Loss of calories and

electrolytes
• Impairing insulin
Persistent
secretion
• Antagonizing insulin dehydration
action. Hypersecretion of stress
• Promoting hormones (epinephrine,
glycogenolysis, cortisol, growth hormone, and
gluconeogenesis, glucagon)
lipolysis, and
ketogenesis
 Effects of Insulinopaenia

Insulin deficiency Elevated counter-

regulatory hormones

Increased
lipid
Lipolysis/ plasma
Impaired concentrati
lipid ons
synthesis (cholesterol
,
triglyceride
s, FFAs)
 Effects of Insulinopaenia
Insulin deficiency FFAs Glucagon excess

ketone bodies
(β- Metabolic
hydroxybutyrat acidosis and
e and Kussmaul
acetoacetate) respiration
 Effects of Insulinopaenia
Glucose, Increase • Progressive
ketones and d losses dehydration
cation of water • Acidosis
excretion in and • Hyperosmolalit
urine electrolyt y
e • Diminished
cerebral oxygen
Impaired consciousness utilization
and coma
 Electrolyte Imbalance in DKA
Potassium
• Intracellular potassium is exchanged for hydrogen ions
• Clearance of potassium by the kidneys (activation of the renin-angiotensin-
aldosterone axis)
Phosphate
• Increased renal excretion required for excretion of excess hydrogen ions (buffer)
Sodium
• Osmotic diuresis
• Vomiting
Pathogenesis of
Diabetic Ketoacidosis.
Adapted from: Nelson
Essentials of
Pediatrics. 6th Edition.
 PRECIPITATING FACTORS

• Poor metabolic control or missed insulin doses

• Illness eg vomiting and dehydration
• Medications – e.g corticosteroids
• Drugs and Alcohol
 HISTORY

• Suspected diabetic: polydipsia, polyuria,

polyphagia, weight loss, vomiting, or
abdominal pain, history of infection or
inciting event
• Known diabetic: The usual insulin regimen,
timing and amount of last dose
 Clinical Presentation of DKA
• Polyuria
• Polydypsia
• Nausea
• Vomiting
• Abdominal pain (DDx: Acute abdomen; paralytic ileus)
• Tachypnoea with deep (Kussmaul) respirations
• Fruity odor (acetone)
• Altered level of consciousness (disorientation to coma)
 Clinical Presentation of DKA
Clinical signs of intravascular volume depletion:
• Tachycardia
• Poor peripheral perfusion
• Decreased skin turgor
Why should children with DKA be rehydrated based upon a presumed fluid
deficit and clinical response rather than using clinical estimates of the degree
of dehydration?
 Severity of DKA in Children

Definitio Mild Moderate Severe

n
Features
Venous pH 7.2-7.3 7.1-7.2 <7.1
Serum 10-15 5-10 <5
HCO3
Data from: 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; 29:1150.
(mEq/L)
 Classification of DKA
NORMAL MILD MODERATE SEVERE
CO2 (mEq/L,
20-28 16-20 10-15 <10
venous)*
pH (venous)* 7.35-7.45 7.25-7.35 7.15-7.25 <7.15
Kussmaul or
Kussmaul depressed
respirations; respirations;
Oriented, alert
Clinical No change oriented but sleepy to
but fatigued
sleepy; depressed
arousable sensorium to
coma
 Laboratory Studies in DKA
• Serum glucose (200 - >1000mg/dL)
• Arterial pH <7.25
• Serum HCO3 <15mEq/L
• Serum sodium may be elevated, low or normal
• BUN can be elevated (prerenal azotemia)
• WBC usually elevated with left shift
 Treatment Principles of DKA
• Careful replacement of fluid deficits
• Correction of acidosis and hyperglycaemia
(insulin administration)
• Correction of electrolyte imbalances
• Monitoring for complications of treatment
 Treatment of Dehydration in
DKA
• The patient with DKA is assumed to be 10% dehydrated
• Initial intravenous fluid bolus (glucose-free, isotonic: NS,
RL) – 10-20mls/kg
• Remaining fluid deficit plus maintenance given in 36 – 48
Tohrs
avoid shifts in serum osmolality, use sodium chloride
0.9% as the initial 4 – 6 hours followed by 0.45% sodium
chloride.
TIME THERAPY COMMENTS

• 10-20 mL/kg IV bolus 0.9% • Fluid boluses should not be

1st hr
NaCl or LR. given in mild/moderate cases

• Insulin drip 0.05 to 0.10

µ/kg/hr
• Insulin given after initial
2nd hr • Fluid maintenance: 0.45%
fluid bolus
until NaCl: plus continue insulin
DKA drip
• Hourly subcutaneous insulin
resoluti 20 mEq/L KCL/500ml
can be given instead of
on • Add 5% glucose if blood
infusion.
sugar ≤250 mg/dL
(14 mmol/L)

Variabl Oral intake with No emesis; CO2 ≥16 mEq/L;

e subcutaneous insulin normal electrolytes
Treatment of Hyperglycaemia in
DKA
• Intravenous fast acting soluble insulin (0.05 - 0.1
U/kg/hour)
• When serum glucose decrease to 250 – 300mg/dL, add
glucose to IV fluids
 Treatment of Acidosis in DKA
• Insulin therapy decreases FFAs production and protein
catabolism and enhance glucose uptake.
• Only use bicarbonate in severe acidosis (pH<7) or
symptomatic hyperkalaemia
• Side effects of bicarbonate:
• increase CO2 across BBB and increase CNS acidosis
• shift of oxyhaemoglobin dissociation curve and tissues hypoxia
• increased risk of cerebral oedema
Treatment of Electrolyte Imbalance
in DKA
• When adequate urine is shown, add potassium to IV fluids
(50% potassium chloride or 50% potassium phosphate –
20-40mEq/L)
• If serum level is >6mEq/L do not add potassium to IV
fluids.
 Monitoring Patients with DKA
• Record and monitor fluid balance and laboratory results
• Initial laboratory results: glucose, sodium, potassium,
chloride, BUN, creatinine, calcium, phosphate, magnesium,
arterial/venous pH, urine analysis
• Measure serum glucose every hour during treatment
• Assess neurologic and mental status at frequent intervals
• Assess for cerebral oedema if headache and deterioration of
mental status occurs
 Complications of DKA
Cerebral Oedema
• Clinically apparent cerebral oedema in 1-5% in DKA
• Cerebral oedema is the most serious complication (Mortality 20-80%
• Typically occurs 6-12 hours after initiation of treatment.
• Risk factors for cerebral oedema:
• Higher initial BUN
• Lower initial PCo2
• Low sodium despite decreasing glucose levels
• Treatment with bicarbonate
 CLINICAL FEATURES OF CEREBRAL
OEDEMA
• Change of consciousness
• Depressed respiration
• Worsening headache
• Bradycardia
• Apnea
• Pupillary changes
• Papilledema,
• Posturing, and seizures.
 Other Complications of DKA
• Intracranial thrombosis or infarction
• Acute tubular necrosis with acute renal failure (severe dehydration)
• Arrhythmias (hypokalemia/hyperkalemia)
• Pulmonary oedema (fluid overload)
• Bowel Ischemia (severe dehydration)
• Peripheral oedema (residual elevation of ADH and aldosterone)
• Hypoglycaemia (insulin therapy)
• Aspiration pneumonia (comatose patients)
 Transitioning to Outpatient Care
• Change to SC insulin once acidosis resolves and patient able to
take oral feeds.
• Give first SC insulin dose 30 – 34 min before discontinuation of
iv insulin infusion
• For known DM1 patients, restart the prior insulin doses
• For new on-set DM1 start insulin at 0.7U/kg/24 hours
(prepubertal) and 1U/kg/24 hours in adolescents
• 2/3 of total insulin is given in the morning and 1/3 in the evening
 Long-Term Glycemic Control

• Glycohemoglobin or hemoglobin A 1c (HgbA1c)

• Reflect the average blood glucose over preceding 3 months

• Assess long-term glycemic control

• Should be measured four times a year

• Used for counseling of patients.

• Targets for children at <7.5%

 Complications of Diabetes

• Retinopathy

• Renal dysfunction (nephropathy)

• Hypertension and hypercholesterolemia