Acute Complication

of
Diabetes Mellitus

Laksmi Sasiarini
Hyperglycemic Crisis
Diabetic Ketoacidosis (DKA)
Hyperosmolar hyperglycemic state (HHS)

Hypoglycemia
Second edition
Update September 2013

American Diabetes Association

(ADA) July 2009
 DKA consists of the biochemical triad of
ketonaemia (ketosis),
hyperglycaemia, and
acidaemia.

 DKA has been considered to be indicative, or even

diagnostic, of type 1 diabetes, but increasingly there are
cases of ketone-prone type 2 diabetes being
recognised.

However, the initial treatment is the same !

 The true incidence is difficult to establish.

 Population based studies range from 4.6 to 8 episodes per

1,000 patients with diabetes.

 DKA remains a significant clinical problem in spite of

improvements in diabetes care.

 In the USA the prevalence has risen, whilst mortality has

fallen.

 Mortality rates have fallen significantly in the last 20 years

from 7.96% to 0.67.
 Cerebral oedema remains the most common cause of
mortality, particularly in young children and
adolescents.

 The main causes of mortality in the adult population

include severe hypokalaemia, adult respiratory distress
syndrome, and co-morbid states such as pneumonia,
acute myocardial infarction and sepsis
These are:
• Hypovolaemia
• Marked hyperglycaemia (30 mmol/L or more) without
significant hyperketonaemia (<3 mmol/L) or
acidosis (pH>7.3, bicarbonate >15 mmol/L)
• Osmolality usually 320 mosmol/kg or more

N.B. A mixed picture of HHS and DKA may occur.

 Whilst DKA presents within hours of onset, HHS comes
on over many days, and consequently the dehydration
and metabolic disturbances are more extreme.

 It is uncommon, but has a higher mortality than DKA.

 There are no recent publications from the UK of

mortality in HHS, but reported series suggest mortality
may have improved though remains high at between 15-
20%.
• Infection (20% - 40%) → urinary tract and lung
• CVA
• Myocardial infarction
• Pancreatitis
• Discontinuation of or inadequate insulin therapy
• Drugs (steroids, sympathomimetics, thiazides)
 History and physical examination

 Laboratory findings

 Differential diagnosis
 History of polyuria, polydipsia, weight loss,
dehydration, weakness, and mental status change.

 Physical findings : poor skin turgor, kussmaul

respiration (DKA), tachycardia, and hypotension,
mental status change (full alertness to profound
lethargy or coma).
Focal neurologic signs and seizures  HHS

 Naussea, vomiting, diffuse abdominal pain are

frequent in pts with DKA (>50%).
• plasma glucose, serum and urine ketones,
electrolytes (with calculated anion gap),
osmolality, arterial blood gases
• blood urea nitrogen/creatinine
• urinalysis
• complete blood count with differential
• electrocardiogram
• bacterial cultures of urine, blood, and throat, etc.
• chest X-ray
 DKA HHS
Mild Moderate Severe
Plasma glucose (mg/dl) > 250 > 250 > 250 > 600
Arterial pH 7.25–7.30 7.00–7.24 < 7.00 > 7.30
Serum bicarbonate (mEq/l) 15–18 10 to 15 < 10 > 18
Urine ketones (+) (+) (+) Small
Serum keton (+) (+) (+) Small
Effective serum osmolality Variable Variable Variable >320
(mosm/kg)
Anion gap > 10 > 12 >12 Variable
Alteration in sensoria and Alert Alert/drowsy Stupor/coma Stupor/coma
mental

Anion gap : (Na+) - (Cl + HCO3) (mEq/l).

Osmolality : (2Na+ + glucose + urea)
 IV fluid (NS)
 Insulin (Continuous IV drip/im)
 K+
 Bicarbonate (pH < 7)

PRECIPITATING FACTOR(S)
 Fluid administration and deficits

There is universal agreement that the most important

initial therapeutic intervention in DKA is appropriate
fluid replacement followed by insulin administration.

The main aims for fluid replacement are:

• Restoration of circulatory volume
• Clearance of ketones
• Correction of electrolyte imbalance
 This should be replaced as crystalloid.

 In patients with kidney failure or heart failure, as well as

the elderly and adolescents, the rate and volume of fluid
replacement may need to be modified.

Typical deficits in DKA in adults :

 Water 100ml/kg
 Sodium 7-10mmol/kg
 Chloride 3-5mmol/kg
 Potassium 3-5mmol/kg
 For 60 kg patient For 100 kg patient
Water 100-220 ml/kg 6-13 litres 10-22 litres

Na+ 5-13 mmol/kg 300-780 mmol 500-1300 mmol

Cl- 5-15 mmol/kg 300-900 mmol 500-1500 mmol

K+ 4-6 mmol/kg 240-360 mmol 400-600 mmol

IV Fluids
Hydration Status ?

Severe hypovolemia Mild dehydration Cardioogenic shock

0.9% NaCl (1 L/h) Hemodynamic

monitoring

Evaluate corrected serum Na+

Serum Na high Serum Na normal Serum Na low

0.45% NaCl (250 – 500 ml/h) depending 0.9% NaCl (250 – 500 ml/h)
on hydration state depending on hydration state

When serum glucose reaches 200 mg% (DKA) or 300 mg/dl

(HHS), change to 5% dextrose with 0.45% NaCl at 150-250 ml/hr
 A fixed rate intravenous RI 0.1 u/kg/h/iv infusion
insulin infusion (FRIII)

If serum glucose does not fall by at least 10% in first hour,

give 0.14 U/kg as IV bolus, then continue previous Rx

When serum glucose reaches 200 When serum glucose reaches

mg/dl, reduce RI infusion to 0.02-0.05
U/kg/hr IV, or give rapid acting insulin at
0.1 U/kg SC every 2 hrs. Keep serum
glucose between 150 and 200 mg/dl
until resolution of DKA
300 mg/dl, reduce RI infusion to
0.02-0.05 U/kg/hr IV. Keep serum
glucose between 200 and 300
mg/dl until px is mentally alert

Insulin has several effects, but the following are the most important when treating
DKA :
• Suppression of ketogenesis
• Reduction of blood glucose
• Correction of electrolyte disturbance
 Initial serum Initial serum Initial serum
K+< 3.3 mEq/L K+ ≥ 5.0 mEq/L K+ 3.3 – 5.5 mEq/L

Hold insulin and give 20- Do not give K+ and Give 20 – 30 mEq K+ in
30 mEq K+/h until K+ > check K+ every 2 h each liter of iv fluid (2/3
3.3 mEq/L as KCL and 1/3 as
KPO4) to keep serum
K+ at 4 – 5 mEq/LmEq
 pH < 6.9 pH ≥ 6.9

NaHCO3 (100 mmol/L) No

dilute in 400 ml H2O + NaHCO3
20 mEq KCl, infuse for 2
hours

Repeat every 2 h until pH ≥ 7.0

Monitor serum K+ every 2 hrs.
 Capillary blood glucose - hourly
 Serum electrolytes and bicarbonate– 2 hourly
initially
 Urine output
 Blood pressure/heart rate
 Mental status
 Keep the serum glucose 150 – 200 mg% until metabolic control is achieved

Check electrolyte, BUN, venous pH, creatinine and glucose every 2 – 4 hours until
stable
After resolution of DKA or HHS and when patient is able to eat, initiate SC
multidose insulin regimen.
To transfer from IV to SC, continue IV indulin infusion for 1-2 hr after SC insulin
begun to ensure adequate plasma insulin levels.
In insulin naïve pts, start at 0.5 U/kg to 0.8 U/kg body weight per day and adjust
insulin as needed.
Continue to look for precipitating factor(s).
Resolution of DKA is defined as
pH > 7.3 units;
bicarbonate > 15.0mmol/L; and
blood ketone level < 0.6mmol/L
(rather than < 0.3mmol/L),
 The ADA Workgroup on Hypoglycemia defined
hypoglycemia in diabetes as “all episodes of abnormally
low plasma glucose concentration that expose the
individual to potential harm ”.

 The cutoff glucose concentration for defining

hypoglycemia is controversial.
 The ADA Workgroup recommended that people with
insulin secretagogue or insulin treated diabetes become
concerned about the possibility of developing
hypoglycemia at a self-monitored (or device estimated)
plasma glucose concentration of ≤ 70 mg/dL (≤ 3.9
mmol/L).
Risks of severe hypoglycaemia associated with
different diabetes treatment

50
Patients affected per year (%)

40

30

20

10

0
Sulphonylurea- Insulin- “Standard” insulin Intensively
treated type 2 treated type 2 therapy in type 1 Treated in type 1
diabetes diabetes diabetes diabetes (DCCT)
Excessive Error by patient, doctor or pharmacist
dosage

Increased Accelerated absorbtion (exercise, injection into

insulin abdomen, change to human insulin)
bioavailability Insulin antibodies, Renal failure, Honeymoon periode

Increased Counter-regulatory hormon deficiencies (Addison,

insulin Hypopituitarism)
sensitivity Weight loss, physical exercise, postpartum,
menstrual cycle variation
Inadequate Missed, small or delayed meals
carbohydrate Anorexia nervosa, Vomiting (gastroparesis), breast
response feeding, failure to cover exercise

Other factors Exercise, alcohol, drugs

Heller SR. Textbook of Diabetes 1, 2003, p.33.1
WHIPPLE’S
TRIAD

HYPOGLYCEMIA
HYPOGLYCEMIA

Low Plasma Glucose Levels

The signs and symptoms of hypoglycemia can be divided
into two categories :
• Autonomic

• Neuroglycopenic
AUTONOMIC
When the blood glucose levels drop significantly, the body releases
epinephrine. This triggers certain processes like releasing the glucose
stored in the liver (glycogen) in an attempt to stabilize the blood glucose
levels.
Epinephrine also affects the nervous system and results in these
characteristic signs and symptoms :
Anxiety
Dizziness
Hunger
Palpitations
Sweating
Trembling
These symptoms are the early warning signs but may be absent in certain
cases. In patients who experience frequent episodes of hypoglycemia, the
body may stop releasing epinephrine. This is known as hypoglycemic-
associated autonomic failure (HAAF) or is also referred to as hypoglycemia
unawareness. The blood glucose levels continue to drop until the
neuroglycopenic symptoms may be evident. It may only be at this point
that the appropriate measures are implemented.
NEUROGLYCOPENIC
As the blood glucose levels continue to drop without any
intervention, the glucose supply to the brain is severely
impaired and may result in the symptoms listed below.
Blurred vision
Confusion
Difficulty concentrating
Drowsiness
Irritability, anger
Poor coordination
Speech difficulty
Autonomic Neuroglycopenic Malaise
Sweating Confusion Nausea
Pounding heart Drawsiness Headache
Tremor Speech difficulty
Hunger Incoordination
Atypical behaviour
Visual disturbance
Circumoral paraesthesia

Heller SR. Textbook of Diabetes 1, 2003, p.33.1

 Hypoglycaemia aware
Blood glucose (mmol/L)
4
Epinephrine Start of brain
Glycaemic thresholds release dysfunction
3
for release of Confusion/loss
Sweating, of concentration
tremor 2
epinephrine and
activation of 1 Coma/seizure
Permanent brain damage
autonomic symptoms
and for Hypoglycaemia unaware
neuroglycopenic Blood glucose (mmol/L)
4
effects in diabetic Start of brain
subject who are aware dysfunction
Epinephrine 3
release Confusion/loss
or unaware of of concentration
2
hypoglycaemia Sweating,
tremor
1 Coma/seizure
Permanent brain damage
Principal metabolic effects of counter-regulation
in response to acute hypoglycaemia
Hypoglycaemia

+
+

ACTH

Glucagon Vasopressin Growth Cortisol

hormone

+
 100
Altered symtoms of hypoglycaemia
Relationships
between the 50

duration of
diabetes (a) 0
100
Sweating and/or tremor

Patients affected (%)

50

(b) 0
100
Severe hypoglycaemia without warning

50

0
(c) 0-9 10-19 20-29 30-39 > 40
Duration of diabetes (years)
 Established
Capillary blood sample
diagnosis

Oral glucose (liquid)

120 cc

Evaluation
Intramuscular glucagon
0.5 – 1 mg Repeat
after 10 ‘

Maintainance
180 – 200 mg% Intravenous glucose 20
10% Dextrose – 30 ml 50% dextrose
Dexamethasone
Principal metabolic effects of counter-regulation
in response to acute hypoglycaemia