Acute complications of diabetes

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Acute complications of diabetes
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• Glucose homeostasis refloects a precise balance
  between hepatic glucose production and
  periphereal glucose uptake and utilization.
• Insulin is thye most important regulator of the
  metabolic equilibrium.

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In the fasting state

• Low insulin levels promote hepatic
  gluconeogenesis and glycogenolysis to prevent
  hypoglicemia

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Postprandially

• A large glucose load elicits a rise in insulin
  and fall in glucagon.

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Diabetes Mellitus
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DM

• Comprises a group of common metabolic disorders
  that share the phenotype of hyperglycemia.

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• In the US, DM is the leading cause of
• End-stage renal disease
• Nontraumatic lower extremity amputations.
• Adult blindness.

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Clasification
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Epidemiology

• In 1998, approximately 16 million individuals in
  the US met the diagnoistic criteria for DM (6 of
  the population)
• The vast majority of these gt90 have type 2

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• Incidence
• 1.5 (20 to 39 years)
• 20 (gt75 years)

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Diagnosis
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Acute complications of diabetes
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• Diabetic ketoacidosis (DKA) and hyperglicemic
  hyperosmolar nonketotic syndrome (HHNS) are life
  threatening acute metabolic complications of
  diabetes mellitus.

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• These complications can be seen in type 1 and
  type 2 diabetes.
• DKA is usually seen in patients with type 1
  diabetes.
• HHNS in patients with type 2 disease.

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• Both disorders are associated with
• Absolute or relative insulin deficiency
• Volume depletion
• And altered mental status.
• Potentially serious complications if not promptly
  diagnosed and treated.

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Diabetic ketoacidosis
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• DKA is a complex disordered metabolic state
  characterized by hyperglycemia, acidosis, and
  ketonuria.

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• DKA still accounts for 50 of diabetes-related
  admissions in young persons
• And 1-2 of all primary diabetes-related
  admissions.

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Incidence

• Exact incidence is not known, but it is estimated
  to be 1 out of 2000.

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• Race Incidence of DKA is higher in whites
  because of the higher incidence of type 1
  diabetes in this racial group.

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• Sex Incidence of DKA is slightly more common in
  females than in males for reasons that are
  unclear.

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• Age DKA is much more common in young children
  and adolescents

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Pathophysiology

• DKA usually occurs as a consequence of absolute
  or relative insulin deficiency that is
  accompanied by an increase in counter-regulatory
  hormones

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• Counter-regulatory hormones (ie, glucagon,
  cortisol, growth hormone, epinephrine).
• This type of hormonal imbalance enhances hepatic
  gluconeogenesis, glycogenolysis, and lipolysis

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• Hepatic gluconeogenesis, glycogenolysis secondary
  to insulin deficiency, and counter-regulatory
  hormone excess result in severe hyperglycemia,
  while lipolysis increases serum free fatty acids.

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• Hepatic metabolism of free fatty acids as an
  alternative energy source (ie, ketogenesis)
  results in accumulation of acidic intermediate
  and end metabolites (ie, ketones, ketoacids).
• Ketones include acetone, beta hydroxybutyrate,
  and acetoacetate.

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• 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.

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• When the accumulated ketones exceed the body's
  capacity of extracting them, they overflow into
  urine (ie, ketonuria).

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• If the situation is not treated promptly, more
  accumulation of organic acids leads to frank
  clinical metabolic acidosis (ie, ketoacidosis),
  with a drop in pH and bicarbonate serum levels.

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• Respiratory compensation of this acidotic
  condition results in rapid shallow breathing
  (Kussmaul respirations).

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• Ketones, in particular beta hydroxybutyrate,
  induce nausea and vomiting that consequently
  aggravate fluid and electrolyte loss already
  existing in DKA.

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• Acetone produces the characteristic fruity breath
  odor of ketotic patients.

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• 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 lactic acidosis.

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• Typical free water loss in DKA is approximately 6
  liters or nearly 100 mL/kg of body weight.
• The initial half of this amount is derived from
  intracellular fluid and precedes signs of
  dehydration.
• The other half is from extracellular fluid and is
  responsible for signs of dehydration.

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• Hyperglycemia, osmotic diuresis, serum
  hyperosmolarity, and metabolic acidosis result in
  severe electrolyte disturbances.

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• The most characteristic disturbance is total body
  potassium loss.
• This loss is not mirrored in serum potassium
  levels, which may be low, within the reference
  range, or even high.

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• 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.

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• A large part of the shifted extracellular
  potassium is lost in urine because of osmotic
  diuresis

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• Patients with initial hypokalemia are considered
  to have severe and serious total body potassium
  depletion.

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• 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.

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• Typical overall electrolyte loss includes
• 200-500 mEq/L of potassium
• 300-700 mEq/L of sodium
• 350-500 mEq/L of chloride.

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• 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.

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Pathogenesis of DKA
Type 1 diabetes
Initiatig event
Insulin Glucagon
Lypolisis
Protein catabolism
Glycerol
FFAs
Amino acids
Ketogenesis
Hyperglicemia
Gluconeogenesis
Ketonemia
Ketonuria
Osmotic diuresis
Volumen depletion Dehydration
Acidosis
Electrolite depletion
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Lipolysis
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Causes

• Patients with type 1 diabetes
• DKA present at diagnosis of type 1 diabetes.
• Omission of insulin injections.
• Intercurrent illness (eg, UTI, vomiting)
• 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 (eg, myocardial infarction,
  pneumonia, prostatitis, UTI)
• Medication (eg, corticosteroids, pentamidine,
  clozapine)IFFERENTIALS

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Syntoms

• Polydipsia
• Polyuria
• Nausea
• Vomiting
• Diffuse abdominal pain.
• Generalized weakness
• Fatigability
• Altered consciousness (frank coma is uncommon)

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Physical Finding

• Dehydration
• Rapid pulse
• Dry tongue and skin
• Hypotension
• Increased capillary refill time
• Patient odor - Characteristic acetone odor
• Signs of acidosis..

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• Signs of acidosis
• Shallow rapid breathing (Kussmaul respiration).
• Abdominal tenderness.
• Disturbance of consciousness

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• Although these signs are not usual in all cases
  of DKA, their presence signifies a severe form of
  DKA

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Laboratory Criteria DKA

• Glucose 300 600
• Arterial pH lt 7.3
• HCO3 lt15
• BUN lt 25
• Osmolality lt320
• Ketones

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Hyperglycemic hyperosmolar nonketotic syndrome

• HHNS

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Definition

• State of extreme hyperglycemia, marked
  dehydration, serum hyperosmolarity, altered
  mental status, and absence of sever ketoacidosis

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• Progression from poor glucose control to overt
  HHNS requires profound hyperglycemia for a
  significant period of time (2 days to 2 weeks),
  which allows an extreme of hyperosmolality an
  dehydration to develop.

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• Occurs in non insulin dependent diabetics and
  in patients deprived of fluid intake.
• Typical patient is usually an elderly, or
  bed-confined diabetic with impaired or no ability
  to communicate thirst.

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• Patients who do not monitor their blood sugar may
  be at increased risk for HHNS

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Clinical Features

• Polyuria
• Orthostatic hypotension
• Neurologic symptoms
• Altered mental status
• Lethargy
• Obtundation
• Seizure
• coma.

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• Absent of nausea, vomiting and abdominal pain,
  and the kussmaul respiration.

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Phathogenesis.

• In HHNS, basal insulin secretion is maintained.
• Insulin levels are adequate to prevent peripheral
  lipolysis in adipose tissue.
• But are not sufficient to allow adequate
  periphereal uptake of glucose or to prevent
  hepatic overproduction of glucose.

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• In patients with HHNS
• Insulin is the major factor suppresing hepatic
  ketogenesis.
• Levels of insulin are not adequete to prevent
  glucagon-induced hepatic gluconeogenesis.

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• HHNS water-deprived, have a subnormal
  osmorregulated thirst and fluid intake.
• As hyperglicemia worsens, hyperosmolality
  develops, and alteration in mental status occur.

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• A depressed level of consciousness leads to a
  decrease in fluid intake, worsening
  hyperglicemia, and hyperosmolality.
• With eventual development of lethargy or coma.

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• In HHNS, the degree of mental status change is
  associated with the degree of hyperosmolality and
  dehydration.

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Pathogenesis of HHNS
Type 2 diabetes
Initiatig event
Insulin Glucagon
Pre Renal Azotemia
Hyperglicemia Hyperosmolality
Glucose uptake
Osmotic diuresis
Thirst
Volumen depletion Dehydration
Electrolyte depletion
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Precipitating factors

• Diabetes
• Acute illness
• Medication
• Substance abuse

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• Diabetes
• New onset
• Poorly controlled
• Cessation of therapy
• Omission of insulin/medication
• CSII (pump) failure.
• Fear of hypoglycemia or a poor understanding of
  diabetes and insulin kinetics may be compained by
  omission or a significant reduction of an insulin
  dose.

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• Acute illness
• Infection (pneumonia, UTI, gastroenteritis,
  sepsis)
• Infarction (cerebral, coronary, mesenteric,
  periphereal)
• Acute pancreatitis
• Sever burns
• Renal Failure
• Myocardial infarction may be symptomatically
  silent in patients with long standing
  diabetes.

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• Medications
• Thiazides
• Beta blockers
• Phenytoin
• Glucocorticoids
• Didanosine
• Somatostatin
• Hyperalimentation

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• Substance abuse
• Alcohol
• Cocaine
• Alcohol and cocaine use were associated with HHNS
  in 44 and 9 of an urban population.

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Syntoms

• Several days of deteriorating glycemic control,
  polyuria, and plydipsia are followed by
  increasing lethargy.
• Alteration in mental status (mild confusion to
  lethargy, stupor, generalized or partial complex
  seizures, myoclonic jerks, chorea, aphasia,
  cerebrovascular accident or coma)

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Physical findings

• Hypotension
• Tachycardia
• Tachypnea
• Fever
• Extreme dehydration
• Shock with periphereal hypoperfusion
• Altered mental status (varying degrees)
• CNS changes in HHNS may mimic a focal neurologic
  event.

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Laboratory Criteria HHNS

• Glucose gt600
• Arterial pH gt 7.3
• HCO3 gt20
• BUN gt30
• Osmolality gt330
• Ketones or small

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Clinical evaluation

• History
• Physical examination
• Evaluation of volume and hydration status should
  proceed immediately.
• Laboratory studies
• Treatment with insulin can begin before the
  results of laboratory studies have been obtained.

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Routinely

• Laboratory studies
• Glucose
• Electrolytes Na, K, CO2, CL
• BUN
• Cr.
• pH
• Anion gap calculated

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Routinely

• Chest radiographs
• Electrocardiograms
• Cultures of blood, urine and sputum
• Cardiac enzymes
• Amylase

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Laboratory results

• Hyperglycemia gt 600
• Hyperosmolarity gt330
• Electrolytes
• Na low, normal, or high
• K low, normal, or high (loss is approximately 5
  to 15 mEq)
• Ca low
• Mg low
• P low
• BUN high (azotemia prerenal)

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Formulas

• Calculation of the anion gap.
• AG (Na) (Cl HCO3)
• Calculation effective serum osmolality
• Efective S osm 2x Na K gl /18
• Correction of serum sodium
• Correction Na Na 1.6 x gluc 100
• 100

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Terapy

• Replacement of fluid losses
• Correction of hyperglycemia and in DKA of
  metabolic acidosis.
• Replacement of electrolyte losses
• Detection and treatment of precipitating causes
  and complications.
• Conversion to a durable diabetes management
  regimen following the correction of DKA or HHNS
• Prevention of recurrence

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• DKA and HHNS require treatment in an intensive
  care (during the first 24-48 hours).
• Close monitoring is essential
• Successful treatment requires frequent monitoring
  of the patiens condition and response to
  interventions.

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• 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.
• Treatment of concurrent infection if present.

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Replacement fluid

• Infuse 1000 to 1500 ml/hr for the initial the
  first 2 hours
• Then decrease the rate of infusion to 500 ml/hr
  the following 2 hours
• Administer 1 liter every 4 hours, depending on
  the degree of dehydration and central venous
  pressure (CVP) readings.

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• Initial correction of fluid loss is either by
  isotonic sodium chloride solution or by lactated
  Ringer solution.
• When the patient becomes euvolemic, the physician
  may switch to half the isotonic sodium chloride
  solution, particularly if hypernatremia exists.

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• When blood sugar decreases to less than 180
  mg/dL, isotonic sodium chloride solution is
  replaced with 5 dextrose

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Correct hyperglycemia

• IV hydration decrease glucose 80 mg/dl/per hour
• Insulin infusion 5 to 10 U/hr
• Optimal rate of glucose decline is 75 to 100
  mg/dl/per hour.

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• Blood tests for glucose should be performed
  hourly (until patient is stable, then every 6 h).

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Insulin

• 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.
• A mix of 25 units of regular insulin in 250 cc of
  isotonic sodium chloride solution usually is
  infused at a rate of 1 microdrip/Kg/min
• 70 kg 7 U/h 7 microdrip/min

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• The blood sugar drops to less than 180 mg/dL,
  then the rate of infusion decreases to 2-3 U/h
  until the ketoacidotic state abates.

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• 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.
• Rapid correction of hyperglycemia and
  hyperosmolarity may shift water rapidly to the
  hyperosmolar intracellular space and may induce
  cerebral edema.

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Replace electrolytes

• Serum electrolyte determinations should be
  obtained hourly (until patient is stable, then
  every 6 h).

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Replace electrolytes
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• 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.

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• 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

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Acid base balance

• Sodium bicarbonate only is infused if
  decompensated acidosis starts to threaten the
  patients life, especially when associated with
  either sepsis or lactic acidosis.
• (EB x 0.3) (Kg) / 3

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• Rapid and early correction of acidosis with
  sodium bicarbonate may worsen hypokalemia and
  cause paradoxical cellular acidosis.

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Treatment of concurrent infection

• In the presence of infection, administer proper
  antibiotics guided by the results of culture and
  sensitivity studies.
• Starting empiric antibiotics on suspicion of
  infection until culture results are available may
  be advisable.

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Mixed syndrome

• DKA and HHNS should be suspected if
• pH lt 7.3
• Ketones are present in the serum
• Osmolarity is greater than 320 mOsm/L

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Mortality

• Even with proper treatment, HHNS has a
  substantially higher mortality than DKA.
• Up to 50 in some clinical series.
• 1 10 of all DKA admissions.
• Better understanding of the pathophysiology of
  DKA and HHNS has resulted in significant
  reduction in the mortality.