ACUTE COMPLICATIONS OF DIABETES MELLITUS

DR ANN KIBIRU-MULI
 introduction
• Diabetic ketoacidosis (DKA) and nonketotic
hyperosmolar state (NKHS) are acute
complications of diabetes.
• DKA is seen primarily in individuals with type 1
DM, and NKHS is seen in individuals with type 2
DM.
• Both disorders are associated with absolute or
relative insulin deficiency, volume depletion,
and altered mental status.
Differences btw DKA & HONK
 Diabetic ketoacidosis (DKA)- Defn
• Diabetic ketoacidosis (DKA) is an acute, major, life-threatening
complication of diabetes.
• Mainly occurs in patients with type 1 diabetes, but can occur in
some px with type 2 DM
• DKA is defined- clinically as an acute state of severe uncontrolled
diabetes that requires emergency treatment with insulin and
intravenous fluids.
• Biochemically, DKA is defined as an increase in the serum
concentration of ketones greater than 5 mEq/L, a blood glucose
level of greater than 250 mg/dL (although it is usually much
higher), blood pH of less than 7.2, and a bicarbonate level of 18
mEq/L or less
 ETIOLOGY- type 1 DM
• DKA present at diagnosis of type 1 diabetes due to acute insulin
deficiency (occurs in 25% of patients)
• Poor compliance with insulin through the omission of insulin
injections either due to lack of patient or guardian education or as a
result of psychological stress, particularly in adolescents
• Bacterial infection and intercurrent illness (e.g. UTI, vomiting)
• Klebsiella pneumoniae (the leading cause of bacterial infections
precipitating DKA)
• Medical, surgical, or emotional stress
• Idiopathic (no identifiable cause)
• Insulin infusion catheter blockage
• Mechanical failure of insulin infusion pump
 Patients with type 2 diabetes
 

• Intercurrent illness (e.g. myocardial infarction,

pneumonia, prostatitis, UTI)
• Medication (e.g. corticosteroids, pentamidine,
clozapine)
 PAthophysiology
• DKA is a complex disordered metabolic state characterized by hyperglycemia,
acidosis, and ketonuria.
• DKA usually occurs as a consequence of absolute or relative insulin deficiency
that is accompanied by an increase in counter-regulatory hormones (i.e.
glucagon, cortisol, growth hormone, and epinephrine).
• This type of hormonal imbalance enhances hepatic gluconeogenesis,
glycogenolysis, and lipolysis
• Hepatic gluconeogenesis, glycogenolysis secondary to insulin deficiency, and
counter-regulatory hormone excess result in severe hyperglycemia, while
lipolysis increases serum free fatty acids.
• Hepatic metabolism of free fatty acids as an alternative energy source (i.e.
ketogenesis) results in accumulation of acidic intermediate and end
metabolites (i.e. ketones, ketoacids).
• Ketones include acetone, beta hydroxybutyrate, and acetoacetate
 Cont,
• Progressive rise of blood concentration of these acidic organic
substances initially leads to a state of ketonemia.
• Natural body buffers can buffer ketonemia in its early stages.
• When the accumulated ketones exceed the body's capacity of extracting
them, they overflow into urine (i.e. ketonuria).
• Imore accumulation of organic acids leads to frank clinical metabolic
acidosis (i.e. ketoacidosis), with a drop in pH and bicarbonate serum
levels.
• Respiratory compensation of this acidotic condition results in rapid
shallow breathing (Kussmaul respirations).
• Ketones induce nausea and vomiting that consequently aggravate fluid
and electrolyte loss already existing in DKA.
• Moreover, acetone produces the characteristic fruity breath odor of
ketotic patients
 Cont,
• Hyperglycemia usually exceeds the renal threshold of glucose absorption and results
in significant glycosuria.
• Consequently, water loss in the urine is increased due to osmotic diuresis induced by
glycosuria.
• This incidence of increased water loss results in severe dehydration, thirst, tissue
hypoperfusion, and, possibly, lactic acidosis
• Typical free water loss in DKA is approximately 6 liters
• Hyperglycemia, osmotic diuresis, serum hyperosmolarity, and metabolic acidosis
result in severe electrolyte disturbances.
• The most characteristic disturbance is total body potassium loss.
• However serum potassium levels, which may be low, within the reference range, or
even high.
• Potassium loss is caused by a shift of potassium from the intracellular to the
extracellular space in an exchange with hydrogen ions that accumulate extracellularly
in acidosis.
 Cont,
• A large part of the shifted extracellular potassium is lost in urine
because of osmotic diuresis.
• Patients with initial hypokalemia are considered to have severe and
serious total body potassium depletion.
• High serum osmolarity also drives water from intracellular to
extracellular space, causing dilutional hyponatremia.
• Sodium also is lost in the urine during the osmotic diuresis
• Typical overall electrolyte loss includes 200-500 mEq/L of potassium,
300-700 mEq/L of sodium, and 350-500 mEq/L of chloride.
• The combined effects of serum hyperosmolarity, dehydration, and
acidosis result in increased osmolarity in brain cells that clinically
manifests as an alteration in the level of consciousness.
 Clinical features- history.
• Insidious increased thirst (i.e. polydipsia) and urination (i.e. polyuria) are the most
common early symptoms of diabetic ketoacidosis (DKA).
• Nausea and vomiting usually occur and may be associated with diffuse abdominal
pain
• Generalized weakness and fatigability may occur
• Altered consciousness in the form of mild disorientation or confusion is a possible
symptom
• Symptoms of possible associated intercurrent infection may include fever, dysuria,
coughing, malaise, and arthralgia, among others
• Acute chest pain or palpitation may occur in association with myocardial infarction
• Patients may present with a history of failure to comply with insulin therapy or
missed insulin injections due to vomiting or psychological reasons
• History of rapid weight loss is a symptom in patients who are newly diagnosed with
type 1 diabetes
 Physical examn
• Signs of dehydration - Weak and rapid pulse, dry tongue
and skin, hypotension, and increased capillary refill time
• Patient odor - Characteristic acetone odor
• Signs of acidosis - Shallow rapid breathing or air hunger
(Kussmaul or sighing respiration), abdominal tenderness,
and disturbance of consciousness
• Signs of intercurrent illness - Myocardial infarction,
urinary tract infection (UTI), pneumonia, and
perinephric abscess, among others
•  
 ddx
• Acute pancreatitis
• Bacteria sepsis
• Metabolic acidosis
• Hyperosmolar coma
• Salicylate toxicity 
 Invx- LAB
• Urine: This test is highly positive for glucose and ketones by dipstick
testing
• Blood and plasma: The blood glucose level usually is higher than 250
mg/dL
• Serum ketones are present
• Arterial blood gases (ABG) frequently show typical manifestations of
metabolic acidosis, low bicarbonate <10 mmol/L (normal 22-26mmol/L),
and low pH (<7.2).
• Serum potassium levels initially are high or within the reference range
due to the extracellular shift of potassium in exchange of hydrogen,
which is accumulated in acidosis, in spite of severely depleted total body
potassium
• The serum sodium level usually is low
 Cont,
• The serum chloride levels and phosphorus levels always are
low
• The anion gap is elevated ([Na + K] - [Cl + HCO 3] >13 mEq/L).
• Plasma osmolarity usually is increased (>290 mOsm/L).
• If plasma osmolarity cannot be directly measured, it may be
calculated with this formula: plasma osmolarity = 2 (Na + K)
+ BUN/3 + glucose/18. Urine osmolarity also is increased
• Even in the absence of infection, CBC shows increased WBC
count
• BUN frequently is increased
 ECG
• This test may reveal signs of acute myocardial
infarction that could be painless in patients with
diabetes, particularly in those with autonomic
neuropathy
• T-wave changes may produce the first warning
sign of disturbed serum potassium levels
• Low T wave and apparent U wave always signify
hypokalemia, while peaked T wave is observed
in hyperkalemia
 TREATMENT
• When treating DKA, the points that must be
considered and closely monitored include
correction of fluid loss with IV fluids;
correction of hyperglycemia with insulin;
correction of electrolyte disturbances,
particularly potassium loss; correction of acid-
base balance; and treatment of concurrent
infection if present
 IV FLUIDS
• Initial correction of fluid loss is either by isotonic
sodium chloride solution or by lactated Ringer solution.
– Administer 1 liter over the first 30 minutes.
– Administer 1 liter over the second hour.
– Administer 1 liter over the following 2 hours.
– Administer 1 liter every 4 hours, depending on the degree of
dehydration and central venous pressure (CVP) readings.
– When the patient becomes euvolemic, the physician may
switch to half the isotonic sodium chloride solution,
particularly if hypernatremia exists.
– When blood sugar decreases to less than 180 mg/dL, isotonic
sodium chloride solution is replaced with 5-10% dextrose with
half isotonic sodium chloride solution.
 2. INSULIN
• The optimal rate of glucose decline is 100 mg/dL/h.
• Do not allow the blood glucose level to fall below 200 mg/dL during the first 4-
5 hours of treatment.
• Hypoglycemia may develop rapidly with correction of ketoacidosis.
• A common mistake is to allow blood glucose to drop to hypoglycemic levels.
• This mistake usually results in a rebound ketosis derived by counter-regulatory
hormones.
• Rebound ketosis requires a longer duration of treatment.
• The other hazard is that rapid correction of hyperglycemia and
hyperosmolarity may shift water rapidly to the hyperosmolar intracellular
space and may induce cerebral edema.
• The initial insulin dose is a continuous IV insulin infusion using an infusion
pump, if available, at a rate of 0.1 U/kg/h. Larger volumes may be easier in the
absence of an intravenous infusion pump (e.g. 60 U of insulin in 500 mL of
isotonic sodium chloride solution at a rate of 50 mL/h).
 correct electrolytes imbalances
• Potassium
– If the potassium level is greater than 6 mEq/L, do not administer potassium
supplement.
– If the potassium level is 4.5-6 mEq/L, administer 10 mEq/h of potassium
chloride.
– If the potassium level is 3-4.5 mEq/L, administer 20 mEq/h of potassium
chloride.
– Monitor serum potassium levels hourly, and the infusion must stop if the
potassium level is greater than 5 mEq/L.
– Monitoring of serum potassium must continue even after potassium infusion
is stopped in the case of (expected) recurrence of hypokalemia.
– In severe hypokalemia, not to starting insulin therapy is advisable unless
potassium replacement is underway in order to avoid potentially serious
cardiac dysrhythmia that may result from hypokalemia.
 4. Correction of acid- base
• Sodium bicarbonate only is infused if decompensated
acidosis starts to threaten the patient's life, especially
when associated with either sepsis or lactic acidosis.
• If sodium bicarbonate is indicated, 100-150 mL of
1.4% concentration is infused initially.
• This may be repeated every half hour if necessary.
• Rapid and early correction of acidosis with sodium
bicarbonate may worsen hypokalemia and cause
paradoxical cellular acidosis.
 Treatment of concurrent infxns.
• Sodium bicarbonate only is infused if decompensated
acidosis starts to threaten the patient's life, especially
when associated with either sepsis or lactic acidosis.
• If sodium bicarbonate is indicated, 100-150 mL of
1.4% concentration is infused initially.
• This may be repeated every half hour if necessary.
• Rapid and early correction of acidosis with sodium
bicarbonate may worsen hypokalemia and cause
paradoxical cellular acidosis.
 Hyperglycemic hyperosmolar state

• Relative insulin deficiency and inadequate fluid intake are the underlying
causes of HHS.
• Insulin deficiency increases hepatic glucose production (through
glycogenolysis and gluconeogenesis) and impairs glucose utilization in skeletal
muscle
• Hyperglycemia induces an osmotic diuresis that leads to intravascular volume
depletion, which is exacerbated by inadequate fluid replacement.
• The absence of ketosis in HHS is not completely understood.
• Presumably, the insulin deficiency is only relative and less severe than in DKA.
• Lower levels of counterregulatory hormones and free fatty acids have been
found in HHS than in DKA in some studies.
• It is also possible that the liver is less capable of ketone body synthesis or
that the insulin/glucagon ratio does not favor ketogenesis
 Clinical features.
• The prototypical patient with HHS is an elderly individual with type 2 DM, with a several
week history of polyuria, weight loss, and diminished oral intake that culminates in mental
confusion, lethargy, or coma
• The physical examination reflects profound dehydration and hyperosmolality and reveals
hypotension, tachycardia, and altered mental status.
• Notably absent are symptoms of nausea, vomiting, and abdominal pain and the Kussmaul
respirations characteristic of DKA.
• HHS is often precipitated by a serious, concurrent illness such as myocardial infarction or
stroke.
• Sepsis, pneumonia, and other serious infections are frequent precipitants and should be
sought.
• In addition, a debilitating condition (prior stroke or dementia) or social situation that
compromises water intake usually contributes to the development of the disorder
• Finally, the development of HHS can be associated with the use of certain medications
(thiazide diuretics, glucocorticoids, and phenytoin).
•  
 invx
• Most notable are the marked hyperglycemia [plasma glucose may
be >55.5 mmol/L (1000mg/dL)], hyperosmolality (>350 mosmol/L),
and prerenal azotemia.
• The measured serum sodium may be normal or slightly low despite
the marked hyperglycemia.
• The corrected serum sodium is usually increased [add 1.6 meq to
measured sodium for each 5.6 mmol/L (100 mg/dL) rise in the
serum glucose].
• In contrast to DKA, acidosis and ketonemia are absent or mild.
• A small anion gap metabolic acidosis may be present secondary to
increased lactic acid.
• Moderate ketonuria, if present, is secondary to starvation.
 treatment
• Volume depletion and hyperglycemia are prominent features of both HHS and DKA.
• Consequently, therapy of these disorders shares several elements
• In both disorders, careful monitoring of the patient's fluid status, laboratory values,
and insulin infusion rate is crucial.
• Underlying or precipitating problems should be aggressively sought and treated.
• In HHS, fluid losses and dehydration are usually more pronounced than in DKA due
to the longer duration of the illness.
• The patient with HHS is usually older, more likely to have mental status changes,
and more likely to have a life-threatening precipitating event with accompanying
comorbidities.
• Even with proper treatment, HHS has a substantially higher mortality than DKA (up
to 15% in some clinical series).
• Fluid replacement should initially stabilize the hemodynamic status of the patient
(1–3 L of 0.9% normal saline over the first 2–3 h).
 Cont,
• Because the fluid deficit in HHS is accumulated over a period of days to weeks,
the rapidity of reversal of the hyperosmolar state must balance the need for
free water repletion with the risk that too rapid a reversal may worsen
neurologic function.
• If the serum sodium > 150 mmol/L (150 meq/L), 0.45% saline should be used.
• After hemodynamic stability is achieved, the IV fluid administration is directed
at reversing the free water deficit using hypotonic fluids (0.45% saline initially
then 5% dextrose in water, D5W).
• The calculated free water deficit (which averages 9–10 L) should be reversed
over the next 1–2 days (infusion rates of 200–300 mL/h of hypotonic solution).
• Potassium repletion is usually necessary and should be dictated by repeated
measurements of the serum potassium.
• In patients taking diuretics, the potassium deficit can be quite large and may
be accompanied by magnesium deficiency.
 Cont,
• As in DKA, rehydration and volume expansion lower the plasma glucose
initially, but insulin is eventually required.
• A reasonable regimen for HHS begins with an IV insulin bolus of 0.1 units/kg
followed by IV insulin at a constant infusion rate of 0.1 units/kg per hour.
• If the serum glucose does not fall, increase the insulin infusion rate by
twofold.
• As in DKA, glucose should be added to IV fluid when the plasma glucose falls
to 13.9 mmol/L (250 mg/dL), and the insulin infusion rate should be
decreased to 0.05–0.1 units/kg per hour.
• The insulin infusion should be continued until the patient has resumed
eating and can be transferred to a SC insulin regimen.
• The patient should be discharged from the hospital on insulin, though some
patients can later switch to oral glucose-lowering agents
 Hypoglycemia- defn
• Hypoglycemia is a syndrome characterized by a reduction
in plasma glucose concentration to a level that may
induce symptoms of low blood sugar.
• Hypoglycemia typically arises from abnormalities in the
mechanisms involved in glucose homeostasis.
• To diagnose hypoglycemia, the Whipple triad
characteristically is present.
• This triad includes the documentation of low blood sugar,
presence of symptoms, and reversal of these symptoms
when the blood sugar level is restored to normal.
 etiology
• Fasting hypoglycemia: Causes of fasting hypoglycemia
usually diagnosed in infancy or childhood include inherited
liver enzyme deficiencies that restrict hepatic glucose
release.
• Inherited defects in fatty acid oxidation
• Drugs - Ethanol, haloperidol, pentamidine, quinine,
salicylates, and sulfonamides
• Exogenous insulin: Insulin-producing tumors of pancreas:
Islet cell adenoma or carcinoma (insulinoma) is an
uncommon and usually curable cause of fasting
hypoglycemia and is most often diagnosed in adults
 Cont,
• Autoimmune hypoglycemia - Insulin antibodies and insulin receptor antibodies
• Surreptitious sulfonylurea use/abuse
• Hormonal deficiencies - Hypoadrenalism (Cortisol), hypopituitarism (growth
hormone) (in children), glucagons deficiency (rare), and epinephrine (very rare)
• Critical illnesses - Cardiac, hepatic, and renal diseases; sepsis with multiorgan failure
• Alimentary hypoglycemia is another form of reactive hypoglycemia that occurs in
patients who have had prior upper GI surgical procedures (gastrectomy,
gastrojejunostomy, vagotomy, pyloroplasty) and allows rapid glucose entry and
absorption in the intestine, provoking excessive insulin response to a meal.
• This may occur within 1-3 hours after a meal.
• Congenital enzyme deficiencies - Hereditary fructose intolerance, galactosemia, and
leucine sensitivity of childhood: In hereditary fructose intolerance and galactosemia,
an inherited deficiency of a hepatic enzyme causes acute inhibition of hepatic
glucose output when fructose or galactose is ingested.
 pathophysiology
• Hypoglycemic symptoms are related to the brain and the sympathetic
nervous system.
• Decreased levels of glucose lead to deficient cerebral glucose
availability (i.e. neuroglycopenia) that can manifest as confusion,
difficulty with concentration, irritability, hallucinations, focal
impairments (e.g. hemiplegia), and eventually, coma and death.
• Stimulation of the sympatho-adrenal nervous system leads to
sweating, palpitations, tremulousness, anxiety, and hunger
• The adrenergic symptoms often precede the neuroglycopenic
symptoms and, thus, provide an early warning system for the patient.
• Studies have shown that the primary stimulus for the release of
catecholamines is the absolute level of plasma glucose
 Clinical features.
• Symptoms of hypoglycemia may be categorized as neurogenic (adrenergic) or neuroglycopenic
• Symptoms due to sympatho-adrenal activation include sweating, shakiness, tachycardia, anxiety, and a
sensation of hunger
• Neuroglycopenic symptoms include weakness, tiredness, or dizziness; inappropriate behavior (sometimes
mistaken for inebriation), difficulty with concentration; confusion; blurred vision; and, in extreme cases, coma
and death
• Postprandial hyperglycemia typically occurs 2-4 hours after eating food, especially when meals contain high
levels of simple carbohydrates.
• Postprandial symptoms are typically due to reactive causes, but some patients with insulinoma also may
present with postprandial symptoms.
• About 4-6 hours after food ingestion, plasma glucose concentrations are 80-90 mg/dL, and rates of glucose
utilization and production are approximately 2 mg/kg/min.
• Glucose production is primarily (70-80%) from hepatic glycogenolysis, with a lesser contribution (20-25%)
from hepatic gluconeogenesis
• Reactive hypoglycemia has been suggested to be more common in people who are insulin-resistant, and it
may be a frequent precursor to type-2 diabetes.
• Therefore, patients who have a family history of type-2 diabetes or insulin-resistance syndrome (ie,
hypertension, hyperlipidemia, obesity) may be at higher risk for developing hypoglycemia
•  
 Treatment- medical care
• If dietary therapy is inadequate, medical care for patients with
fasting hypoglycemia may include intravenous (IV) glucose infusion.
• Intravenous glucagon that inhibits insulin secretion is also effective.
• Frequent meals/snacks are preferred, especially at night, with
complex carbohydrates
• Patients should avoid simple sugars, increase the frequency of their
meals, and reduce the size of their meals.
• Because exercise burns carbohydrates and increases sensitivity to
insulin, patients with fasting hypoglycemia should avoid significant
activity. On the other hand, patients with reactive hypoglycemia
often find that their symptoms improve after embarking on a
routine exercise program