ACUTE COMPLICATIONS OF
DIABETES MELLITUS
Introduction
Classification of acute complications of DM
1. Hypoglycemia
2. Diabetic Ketoacidosis (DKA)
3. Hyperosmolar Hyperglycemic State/Coma
(HHS/HHC)
Hypoglycemia
• Occurs from a relative excess of insulin in the blood and is
characterized by below-normal blood glucose levels.
• Characterized by symptoms of sympathetic nervous system
stimulation or central nervous system dysfunction
• The glucose level at which an individual becomes symptomatic is
highly variable (threshold generally at < 55 mg/dL or < 3.0
mmol/l).
• There is resolution of the symptoms/signs when the plasma
glucose concentration is raised
Hypoglycemia ...
Etiology
• Excess inslin or oral hypoglycemics
• Missed meals
• Renal disease/CKD (↓insulin and SU clearance)
• ↓glucose production (hypopituitarism, adrenal insufficiency, glucagon
deficiency, hepatic failure)
• Other causes include idiopathic causes, insulinoma, post bariatric
surgery (postgastrectomy or gastric bypass), and miscellaneous causes.
Hypoglycemia ...
Clinical manifestations
CNS: headache, visual changes, altered mental status,
weakness, seizure, loss of consciousness
Autonomic: hunger, diaphoresis, palpitaions, tremors
• The Whipple triad
– Symptoms consistent with HYPOGLYCEMA
– Low plasma glucose conc. (measured with a
precise method)
– Relief of symptoms after plasma glucose level is
RAISED
Hypoglycemia ...
(Treatment)
• The mainstay of therapy for hypoglycemia is glucose
• Glucose tables, paste, fruits juice are the first-line treatment for
patients who can take PO(per oral)
• IV access available:
– 2 ml/kg of 50% Dextrose
– 4 ml/kg of 25%Dextrose
– 6-10 ml/kg of 10% Dextrose
• If no other Dextrose is available, give 20 ml/kg boluses of IV
Dextrose 5%
• Re-assess blood glucose 30 minutes after every bolus.
Treatment ...
• Can give glucagon 0.5 – 1 mg intramuscularly (IM) or
subcutaneously (SC)
• Surgery
– Definitive treatment for fasting hypoglycemia caused by a
tumor (e.g benign islet-cell adenomas) is surgical
resection.
Diabetic Ketoacidosis (DKA)
• The three major metabolic derangements in DKA are:
– Hyperglycemia
– Ketosis
– Metabolic acidosis
• Lack of insulin leads to mobilization of fatty acids from
adipose tissue because of the unsuppressed adipose cell
lipase activity that breaks down triglycerides into fatty acids
and glycerol.
– The increase in fatty acid levels leads to ketone production by the
liver.
• Most often seen in Type 1 DM but also can be present in
Type 2 DM who have predominantly secretory defects
DKA
• Consists of hyperglycemia (blood glucose levels >250
mg/dL or >13 mmol/l), low bicarbonate (<15 mEq/L),
and low pH (<7.3), with ketonemia and moderate
ketonuria.
• Hyperglycemia due to ↑gluconeogenesis,
↑glycogenolysis & ↓glucose uptake into cells.
– leads to osmotic diuresis, dehydration, and a critical loss of
electrolytes.
– leads to a shift of water and potassium from the intracellular
to the extracellular compartment.
DKA
• Ketosis due to insulin deficiency →mobilization and
oxidation of fatty acid, ↑ketogenesis, ↑ ketogenic
state of the liver, ↓ ketone clearance
• Metabolic acidosis is caused by the excess ketoacids
that require buffering by bicarbonate ions; this leads
to a marked decrease in serum bicarbonate levels
DKA
• Inadequate insulin leads
to energy stores from
fat and muscle to be
broken down into fatty
acids and amino acids
• These precursors are
transported to the liver
for conversion to
glucose and ketones
Precipitating factors for DKA
(the I’s)
• Insulin deficiency (i.e failure to take enough insulin)
• Iatrogenesis (glucocorticoids)
• Infections (Pneumonia, UTI)
• Inflammation (pancreatitis, cholecysytitis)
• Ischemia or Infarction (myocardial, cerebral, gut)
• Intoxication (alcohol, drugs)
Precipitants ...
• Others
– endocrine disorder(hyperthyroidism,
pheochromocytoma)
– newly diagnosed diabetes (presenting
manifestation)
Clinical manifestations - DKA
• Polyuria, polydipsia and dehydration
• Nausea and Vomiting, abdominal pain
• Kussmaul’s respiration (deep) to compensate for
metabolic acidosis with odor of acetone
• Alerted mental state (somnolence, stupor, coma)
Diagnostic studies
• Serum glucose levels • CBC count
• Serum electrolyte levels • BUN and creatinine
(eg, K+, Na+, Cl-, Mg, levels
Ca2+, phosphorus) • Urine and blood
• Bicarbonate levels cultures if intercurrent
• Amylase and lipase infection is suspected
levels • ECG (in patients with
• Urine dipstick comorbidities)
• Ketone levels
• ABG measurements
Treatment - DKA
• MUST be admitted to an intensive care unit
(ICU)
Goals
1. Correction of Fluid Loss
2. Correct/Reduction of hyperglycemia
3. Correction of electrolyte imbalance
4. Correction of Acid-Base Balance
5. Investigation and treat precipitating factors
Correction of Fluid Loss
• Fluid resuscitation is a critical part of treating patients with
DKA
• By isotonic sodium chloride solution
– 1-3 L during the first hour.
– 1 L during the second hour.
– 1 L during the following 2 hours
– 1 L every 4 hours, depending on the degree of dehydration
• When blood sugar decreases to less than 14mmol/l, isotonic
sodium chloride solution is replaced with 5% dextrose
Correct/Reduction of hyperglycemia
• Insulin should be started about an hour after IV fluid
replacement is started
• Initial insulin dose is a continuous IV insulin infusion
using an infusion pump, if available, at a rate of 0.1
U/kg/h.
– Continue with insulin drip until Anion gap (AG) is normal or
ketone free/clear
– When AG normal → SC insulin
Correction of electrolyte imbalance
• Potassium level
– > 6 mEq/L, do not administer potassium
supplement.
– 4.5-6 mEq/L, administer 10 mEq/h of potassium
chloride.
– 3-4.5 mEq/L, administer 20 mEq/h of potassium
chloride.
• Infusion must be stopped if the potassium
level is greater than 5 mEq/L
Correction of Acid-Base Balance
• Bicarbonate typically is not replaced as acidosis will
improve with treatments (IV fluids ad insulin)
• Replete if Ph < 7 or if cardiac instability
Investigation and treat precipitating factors
• Starting empiric antibiotics on suspicion of
infection until culture results are available
Hyperosmolar Hyperglycemic State (HHS)
• Is a life-threatening emergency less common
than diabetic ketoacidosis (DKA)
• Has a much higher mortality rate, reaching up
to 5-10%
• Is most commonly seen in patients with type
2 DM
HHS
• Is characterized by
– hyperglycemia,
– hyperosmolarity, and
– dehydration without significant ketoacidosis.
• Most patients present with severe dehydration (vs
DKA)
– Average fluid loss up to 8 – 10 L
• Hyperglycemia → osmotic diuresis →volume
depletion
Precipitants - HHS
• Same as for DKA, but also include dehydration
– reduced fluid intake
– any illness that predisposes to dehydration may lead to HHS
Clinical manifestations & diagnostic studies-
HHS
• HHS usually develops over a course of days to weeks,
– unlike DKA, which can develop in hours to a few days.
• Preceded by illness or comorbidity (eg, dementia,
immobility) with increasing dehydration due to inadequate
oral hydration or water loss (eg, vomiting, diarrhea).
• Polydipsia and polyuria, depending on hydration status
• Advanced HHS: altered mental status, seizures and/or
coma.
Diagnostic studies/workup
• Plasma glucose level of 600 mg/dL (>33.3mmol/l) or greater
• Effective serum osmolality of 320 mOsm/L or greater
• Profound dehydration, up to an average of 9L
• Serum pH greater than 7.30
• Bicarbonate concentration greater than 15 mEq/L
• Small ketonuria and low to absent ketonemia
• Usually ↑BUN & creatinine
Treatment HHS
GOALS
– Aggressive hydration while maintaining electrolyte
homeostasis
– Correct hyperglycemia
– Treat underlying diseases
– Monitor and assist cardiovascular, pulmonary, renal, and
central nervous system (CNS) function
• All patients diagnosed with HHS require hospitalization-
intensive care unit (ICU)
Aggressive hydration
• Aggressive intravascular volume replacement
is always indicated as the first line of therapy
– Isotonic sodium chloride solution
• Average fluid loss up to 8 – 10 L
Correction of hyperglycemia
• Many patients with HHS respond to fluids
alone
• IV insulin in dosages similar to those used in
DKA can facilitate correction of hyperglycemia
• Airway management is the top priority.
• In comatose patients, endotracheal intubation may
be indicated.
