• A potentially life-threatening complication in patients with

diabetes mellitus

• Predominantly in those with type 1 diabetes……. but it can

also occur in those with type 2 diabetes also

• Results from a shortage of insulin; in response the body

switches to burning fatty acids and producing acidic ketone

bodies that cause most of the symptoms and complications

• Mortality of less than 1% with adequate and timely treatment

HISTORY:

• 1886 – Royal College of Physicians, London – Lecture by Julius

Dreschfeld

• 100% mortality till 1920, discovery of Insulin

• 1930 - Mortality came down to 29%

• 1950 – Less than 10%

• 1936 – Cerebral oedema described by doctors at Philadelphia

• 1987 – ketosis prone type 2 DM, aka. "idiopathic type 1 diabetes",

"Flatbush diabetes", "atypical diabetes" and "type 1.5 diabetes"

EPIDEMIOLOGY:

Diabetic ketoacidosis occurs in 4.6–8.0 per 1000 people

with type 1 diabetes annually

About 30% of children with type 1 diabetes receive their

diagnosis after an episode of DKA.

• Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA (December 2006).

"Hyperglycemic crises in adult patients with diabetes: a consensus statement from

the American Diabetes Association“

• Silverstein J, Klingensmith G, Copeland K, et al. (January 2005)."Care of children and

adolescents with type 1 diabetes: a statement of the American Diabetes Association"

CAUSES:

• Intercurrent illness (pneumonia, influenza, gastroenteritis, a urinary

tract infection)

• Pregnancy

• Inadequate insulin administration (e.g. defective insulin pen device)

• Myocardial infarction

• Stroke

• Use of cocaine

PRECIPITATING

FACTOR

DKA in type 2 DM – The “Ketosis-prone type 2 DM”

A study evaluating 138 consecutive admissions for DKA at

a large academic center observed that 21.7% had type 2

diabetes

(Newton CA, Raskin P: Diabetic ketoacidosis in type 1 and type 2 diabetes: clinical and

biochemical differences. Arch Intern Med)

“When DKA occurs in patients with type 2 diabetes, the presumed mechanism of

ketoacidosis is the combination of relative insulin deficiency and increased secretion of

glucagon (as well as other counteregulatory hormones such as cortisol, catecholamines,

and growth hormone) in response to stress from 1) overwhelming infection, 2) infarction

of tissue, or 3) other severe illness. The elevated catecholamines further suppress insulin

secretion to perpetuate a downward spiral. The increased glucagon-to-insulin ratio

causes a mismatch that promotes unregulated lipolysis and proteolysis with subsequent

uninterrupted formation of ketoacidosis”.

More common in African, African-American and Hispanic people. Their

condition is then labeled "ketosis-prone type 2 diabetes"

SIGNS & SYMPTOMS: usually evolve over the period of about 24 hours

• Nausea and vomiting, pronounced thirst, excessive urine production and

abdominal pain, high blood sugar levels

• In severe DKA, breathing becomes labored and of a deep, gasping character, a

state referred to as "Kussmaul respiration” - respiratory compensation for a

metabolic acidosis

• Ketotic/fruity odor in breath

• “Coffee ground vomiting” (vomiting of altered blood) occurs in a minority of

patients, d/t esophageal erosion

• Marked decrease in the level of consciousness

• Clinical evidence of dehydration, such as a dry mouth and decreased skin turgor,

the average adult DKA patient has a total body water shortage of about 6 liters (or

100 mL/kg)

• Severe dehydration can lead to tachycardia and hypotension

• Small children with DKA are relatively prone to cerebral edema, 0.3–1.0% of

children, 20–50% mortality

INVESTIGATIONS & DIAGNOSIS:

• May be diagnosed when the combination of hyperglycemia (high blood sugars), ketones

in the blood(negative: < 1 mg/dl) or in urine and acidosis are demonstrated

• In addition to the above, blood samples are usually taken to measure urea and creatinine

(measures of kidney function, which may be impaired in DKA as a result of dehydration)

and electrolytes

• High anion gap; due to consumption of bicarbonate and CO2 loss in hyperventilation

• Markers of infection (complete blood count, C-reactive protein) and acute pancreatitis

(amylase and lipase) may be measured

• Chest radiography and urinalysis are usually performed

• If cerebral edema is suspected because of confusion, recurrent vomiting or other

symptoms, computed tomography may be performed to assess its severity and to

exclude other causes such as stroke

The American Diabetes Association categorizes DKA in adults into one

of three stages of severity:

A 2004 statement by the European Society for Paediatric

Endocrinology and the Lawson Wilkins Pediatric Endocrine Society (for

children) uses slightly different cutoffs, where:

• mild DKA is defined by pH 7.20–7.30 (bicarbonate 10–15 mmol/l)

• moderate DKA by pH 7.1–7.2 (bicarbonate 5–10)

• severe DKA by pH<7.1 (bicarbonate below 5).

Grade pH Bicarbonate

(mmol/L)

Mental

State

Mild 7.25-7.30 15-18 Alert

Moderate 7.00-7.24 10-14.9 Drowsy

Severe <7.00 <10 Stupor to

coma

RESOLUTION:

Resolution of DKA is defined as general improvement in

the symptoms, such as the ability to tolerate oral nutrition

and fluids, normalization of blood acidity (pH>7.3), and

absence of ketones in blood (<1 mmol/l) or urine. Once this

has been achieved, insulin may be switched to the usual

subcutaneously administered regimen.

COMPLICATIONS:

• Cerebral Oedema – Most dangerous

• Pulmonary Oedema

• ARDS

• Electrolyte imbalance

• CCF

• Acute MI

• Acidosis & Cardiac arrest

• Acute Kidney Failure

• Sepsis syndrome and shock

PROGNOSIS

The overall mortality rate for DKA is 2% or less. The

presence of deep coma at the time of diagnosis,

hypothermia, and oliguria are signs of poor prognosis.

The prognosis of properly treated patients with diabetic

ketoacidosis is excellent, especially in younger patients if

intercurrent infections are absent. The worst prognosis

usually is observed in older patients with severe

intercurrent illnesses (e.g. myocardial infarction, sepsis, or

pneumonia), especially when these patients are treated

outside an intensive care unit.