Medicine 2 (Endocrinology) I Lecture #6B

ACUTE COMPLICATIONS OF DIABETES MELLITUS

Dr. Salvacion T. De Vera Sible | Oct. 9, 2021

OUTLINE:
I. ACUTE COMPLICATIONS OF DIABETES MELLITUS
A. Diabetic Ketoacidosis
B. Hyperglycemic Hyperosmolar State
C. Diagnostic Criteria for DK & HHS
D. Causes of DKA/ HHS
E. Pathogenesis of DKA/HHS
II. THERAPEUTIC OBJECTIVES
III. CORNERSTONE OF THERAPY
A. Monitoring
B. Replacement of fluids and electrolytes
C. Insulin therapy
D. Potassium replacement
E. Bicarbonate therapy
IV. RESOLUTION OF DKA AND HHS
V. IV INSULIN IS TAPERED AND SHIFTED TO MULTIPLE
DOSE SUBQ INSULIN
VI. POSSIBLE COMPLICATIONS OF DKA Figure 1. Manifestations of Diabetic Ketoacidosis
VII. HYPOGLYCEMIA
A. Pathophysiology
B. Clinical Manifestations
C. Treatment
D. Prevention
VIII. REFERENCES
IX. APPENDIX LEGEND:
Black for powerpoint, red for audio lecture, blue for book

ACUTE COMPLICATIONS OF DIABETES MELLITUS

• Diabetic Ketoacidosis (DKA) and Hyperglycemic
Hyperosmolar State (HHS)
o Are acute, severe disorders directly related to
diabetes
o DKA was formerly considered a hallmark of type
1 DM, but can also occur in individuals with type
2 DM
o Both disorders are associated with absolute or
Figure 2. Triad of DKA
relative insulin deficiency, volume depletion, and
acid base abnormalities.
Hyperglycemic Hyperosmolar State
Diabetic Ketoacidosis • HHS is used to replace the terms:
• Hyperglycemic hyperosmolar coma
• Most common acute hyperglycemic complication of
o Coma may occur in less than 50% of HHS
diabetes
patients despite a high serum osmolality
• Nausea and vomiting = prominent symptoms, their • Hyperglycemic hyperosmolar non-ketotic state
presence in an individual with diabetes warrants o Because mild ketosis may be observed in
laboratory evaluation for DKA. patients with hyperglycemic hyperosmolar state
• Abdominal pain may be severe and can resemble
acute pancreatitis or ruptured viscus.
• Annual incidence estimated from 4-8/1000 patient
admissions with diabetes.
• Accounts for 45% increase in hospital admissions
but has decline in mortality by 22%

Figure 3. Clinical Features of HHS

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 Medicine 2 (Endocrinology) I Lecture #6B
ACUTE COMPLICATIONS OF DIABETES MELLITUS
Dr. Salvacion T. De Vera Sible | Oct. 9, 2021

Diagnostic Criteria for DKA & HHS also lead to increase delivery of free fatty acids into
the liver resulting in ketogenesis and ketosis.
• While in hyperosmolar hyperglycemic state,
because of the relative insulin deficiency, it may also
lead to increase hepatic glucose production through
glycogenolysis or gluconeogenesis and decrease
the uptake of glucose in the peripheral tissues
leading to hyperglycemia, glucosuria, and osmotic
diuresis leading to dehydration and decreased renal
perfusion and hyperosmolarity.
• While the pathogenesis of DKA and HHS are similar,
differences lie in: HHS
o There is greater dehydration
o There is sufficient insulin to prevent excessive
lipolysis.

*See appendix for the diagram of pathogenesis

Figure 4. Diagnostic Criteria for DKA & HHS
For DKA
THERAPEUTIC OBJECTIVES
• Restoration of circulatory volume and tissue
perfusion
• A steady but gradual reduction of serum glucose and
plasma osmolality
• Correction of electrolyte imbalances
• Resolution of ketoacidosis in DKA
• Recognition and treatment of any precipitating
causes or comorbid conditions.

CORNERSTONE OF THERAPY
Monitoring
• Serum glucose values must be checked every 1–2
hours during treatment.
• Serum electrolytes, phosphate, and venous pH
should be assessed every 2–6 hours depending on
the clinical condition and response of the patient.
Figure 5. Laboratory Findings in DKA & HHS
Replacement of Fluids and Electrolytes
Causes of DKA/HHS • Loss of water in DKA averages 5 to 6 L and in HHS
• DKA is the initial presentation in 20 to 30% of may be as high as 9 L.
patients with type 1 DM. • Initial choice: isotonic saline infused at a rate of 1 to
• Stressful precipitating event that results in increased 1.5 L the first hour.
catecholamines, cortisol, glucagon. • Next 2 hours by either 0.45% or 0.9% NaCl given at
o Infection (pneumonia, UTI) 500–1000 ml/hour with subsequent fluid
o Alcohol, drugs replacement dependent on the status of hydration,
o Stroke serum electrolyte levels, and urinary output.
o Myocardial Infarction • Goal: to replace the estimated water deficit over the
o Pancreatitis first 36 hours.
o Trauma
o Medications (steroids, thiazide diuretics) Insulin Therapy
o Non-compliance with insulin
• IV bolus of regular insulin (0.1 U/kg body weight)
followed by a continuous infusion of low-dose
Pathogenesis of DKA/HHS regular insulin at a concentration of 0.1 U/kg per
• DKA results from both relative & absolute insulin hour.
deficiency combined with increased • Expected decrease in CBG: 50 to 100 mg/dl per
counterregulatory hormones (glucagon, hour.
catecholamines, cortisol, and growth hormone). • If the serum glucose does not fall by 10% of the initial
• This is aggravated by stressful condition such as value in the first hour, the initial IV bolus should be
infection and insulin deficiency. repeated hourly until a steady decline in glucose.
• The decreased ratio of insulin to glucagon would • When CBG reaches 200mg/dl in DKA or 300mg/dl in
lead to gluconeogenesis, glycogenolysis, and HHS, shift IV to dextrose in saline, and the insulin
ketone body formation in the liver, and this would

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 Medicine 2 (Endocrinology) I Lecture #6B
ACUTE COMPLICATIONS OF DIABETES MELLITUS
Dr. Salvacion T. De Vera Sible | Oct. 9, 2021
infusion rate is decreased to 0.05 U/kg per hour. (to
avoid cerebral edema)
• Titrate insulin infusion to maintain the blood glucose
between 150 and 200 mg/dl in DKA and 250 to 300
mg/dl in HHS.
• Whenever rapid-acting or regular subcutaneous
insulin is started, intravenous insulin infusion should
be allowed to overlap for one to two hours in order to
prevent a rebound of ketoacidosis or hyperglycemia.
Potassium Replacement
• Repletion should not begin until serum potassium
falls to less than 5.0 or 5.2 meq/L
• Urine output is at least 50 ml/hour.
Bicarbonate Therapy
• Beneficial ONLY if patient is severely acidotic or
nearing cardiorespiratory collapse.
o pH between 6.9 and 7.0 it may be prudent to give
50 mmol of bicarbonate (1 ampule) in 200 ml of
sterile water with 10 mEq/L KCl per hour over 2
hours
• HCO3 + H = carbonic acid = H2O + CO2 in ECF.
• CO2 readily enters cells, where reverse reaction
occurs, i.e., H is produced intracellularly, leading to
intracellular acidosis.
• May impair cardiac function and may lead to
hypokalemia.
• Adverse effects on oxyhemoglobin dissociation
curve: reduce tissue oxygenation and tissue
hypoxia.
• Overshoot alkalosis
*See appendix for the Protocol for Management of Adult
Patients with DKA or HHS
RESOLUTION OF DKA AND HHS
• Normalization of the serum anion gap to <12meq/L
• Absence of beta-hydroxybutyric acid by direct
testing
o Ketonemia and ketonuria may last for more than
36 hours because of the slower removal of
acetone, in part through the lungs.
o So acetone may still be positive even though
such patients are no longer in ketoacidosis
• For HHS: Effective osmolality is below 320
mOsmol/kg and are mentally alert
• The patient is able to eat
What is the best test to monitor the resolution of ketosis?
a. Plasma ketone
b. Urine Ketone
c. Anion gap
d. Plasma Osmolality
Ans: Plasma Ketone
• Plasma ketone is the best test to monitor resolution of
ketosis because this is done by b-hydroxybutyrate
testing reflecting the true ketone body level
• Acetoacetate is measure by nitroprusside method and
may cause a false positive test.
ENOVISO
IV INSULIN IS TAPERED AND SHIFTED TO
MULTIPLE DOSE SUBCUTANEOUS INSULIN
• Serum glucose less than 200 mg/ml in DKA or 250
to 300 mg/kg in HHS.
• Serum anion gap < 12 meq/L (or less than upper
normal limit for the local laboratory.
• Serum bicarbonate >18 meq/L.
• Venous pH >7.30
POSSIBLE COMPLICATIONS OF DKA
• Cerebral Edema
o Etiology: not well established
o Rare, but life threatening
o Usually in pediatric, adolescent patients
o Mechanism: increased cerebral perfusion from a
vasogenic mechanism rather than osmotic cell
swelling
o Symptoms: Headache and Altered mental status
Treat with Mannitol and Hyperventilation
• Hypoxemia
o Reduction in colloid osmotic pressure leading to
increased lung water content and decreased lung
compliance
• Rarely, Non-cardiac pulmonary edema
KEYPOINTS
• DKA/HHS are common
• More type 2 diabetes are admitted for emergencies
than type 1
• Potentially fatal condition if missed or undermanaged
• Dehydration – Isotonic fluids are the preferred first line
IVF
• Switch to D5 IVF (CBG 200-300) so more insulin can
be given
• Safe glucose lowering is 50-100 mg/dL per hour
• Total body potassium is almost always deficient
• Always replace K+ unless level >5.3 or oliguric
• Hold insulin bolus if hypokalemic <3.3
• Bicarbonate is given only a very few selected situations
HYPOGLYCEMIA
• Most commonly caused by drugs used to treat
diabetes mellitus or by exposure to other drugs,
including alcohol
• Documented by Whipple’s triad:
1. Symptoms consistent with hypoglycemia
2. Low plasma glucose concentration measured
with a precise method (not a glucose monitor)
3. Relief of those symptoms after the plasma
glucose levels is raised
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 Medicine 2 (Endocrinology) I Lecture #6B
ACUTE COMPLICATIONS OF DIABETES MELLITUS
Dr. Salvacion T. De Vera Sible | Oct. 9, 2021

Treatment
• Oral treatment with glucose tablets or glucose –
containing fluids, candy, or food
• Unable or unwilling:
o Parenteral therapy = is necessary
o Intravenous glucose (25g) should be given and
followed by a glucose infusion
o If intravenous therapy is not practical: SC or IM
Glucagon 1.0 mg in adult can be given

Prevention
• Offending drugs can be discontinued or their doses
reduced
• Underlying critical illness can be treated
• Cortisol and growth hormone can be replaced if
deficient
• Surgical, radiotherapeutic, or chemotherapeutic
reduction of non-islet cell tumor can alleviate
hypoglycemia

END OF TRANSCRIPTION

REFERENCES
• Doc Sible’s powerpoint presentation
Figure 6. Causes of Hypoglycemia in Adults • Harrison’s 19th edition

Pathophysiology
• Hypoglycemia activates proinflammatory, pro-
coagulant and pro-atherothrombotic responses in
T1DM, T2DM, and non-diabetic individuals.
o increase platelet aggregation
o reduce fibrinolytic balance (inc. plasminogen
activator inhibitor-1)
o increase intravascular coagulation.
• Hypoglycemia also reduces protective nitric oxide-
mediated arterial vasodilator mechanisms in healthy,
T1DM, and T2DM individuals.

Clinical Manifestations
• Neurogenic (or autonomic) symptoms of
hypoglycemia
o Are the result of the perception of physiologic
changes caused by the CNS – mediated
sympathoadrenal discharge triggered by
hypoglycemia
▪ Adrenergic symptoms (mediated by
norepinephrine released from the sympathetic
postganglionic neurons) and also epinephrine
released from the adrenal medulla)
- Palpitations, tremors, and anxiety
▪ Cholinergic symptoms
- Sweating, hunger, and paresthesia
• Neuroglycopenic symptoms of hypoglycemia
o Are the direct result of central nervous system
(CNS) glucose deprivation
o Include:
1. behavioral changes
2. confusion
3. fatigue
4. seizure
5. loss of consciousness
6. death – when severe and prolonged

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 Medicine 2 (Endocrinology) I Lecture #6B
ACUTE COMPLICATIONS OF DIABETES MELLITUS
Dr. Salvacion T. De Vera Sible | Oct. 9, 2021

APPENDIX

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 Medicine 2 (Endocrinology) I Lecture #6B
ACUTE COMPLICATIONS OF DIABETES MELLITUS
Dr. Salvacion T. De Vera Sible | Oct. 9, 2021

Summary of Manangement of Diabetic Ketoacidosis

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