Lecture 9: Hypoglycemia Flashcards
What are characteristics of hypoglycemia?
A sign not a diagnosis
Results when utilization exceeds production
Brain, muscle, red and white cells, renal medulla main tissues of glucose use
Brain is dependent on glucose or it can utilize ketone bodies
What are the hormones that control glucose?
- insulin
- glucagon
- epinephrine
- cortisol
- growth hormone
What does cortisol do in terms of glucose homeostasis?
- stimulates gluconeogenesis
What does epinephrine do in terms of glucose homeostasis?
Stimulates
i. glycogenolysis ii. lipolysis iii. ketogenesis
What does growth hormone do in term of glucose homeostasis?
Stimulates Lipolysis
What are Whipple’s triad of hypoglycemic symptoms?
- symptoms of hypoglycemia
- measured low glucose at time of symptoms
- correction of symptoms with food or glucose
Characteristic but non-specific
What is the definition of hypoglycemia?
Activation of glucose counterregulatory systems: 50-55 mg/dl
Cognitive dysfunction = 45-50 mg/dl
What are the two symptoms of hypoglycemia?
- neurogenic
- the result of perception of physiological changes caused by CNS mediated sympathetic nervouse discharge
-includes adrenergic and cholinergic responses
-adrenergic = palpitations, tremor, anxiety
-cholinergic = sweating, hunger, paresthesis
- the result of perception of physiological changes caused by CNS mediated sympathetic nervouse discharge
- Neuroglycopenic
-arise from failure of brain function caused by deficient glucose
-confusion, dizziness, fatigue, inability to concentrate
Neurogenic symptoms usually preced neuroglycopenic symptoms (so tremor before fainting)
What is the significance of beta hydroxybutyrate levels?
High Bhydroxybutyrate levels means LOW insulin since insulin inhibits FFA generation (betahydroxybutyrate
What is the significance of acetoacetate?
Shows that body is ketotic
Ketone bdies
That means insulin problem most likely
What is late dumping syndrome?
Hyperinsulinemic hypoglycemic after gastric surgery
What is the most common cause of persistent hypoglycemia in children and adults?
Hyperinsulemic hypoglycemia
What is the diagnostic criteria in hyperinsulinemic hypoglycemia?
Hyperinsulinemia (over 2 mU/mL)
High C-peptide (over .2 mmol/L)
Hypofatty acidemia (plasma FFA < 1.5 mmol/L)
Hypoketonemia
Glycemic response to glucagon
Makes sense because the FFA and ketone levels are VERY low meaning that insulin is leading to hypoglycemia
What is an insulinoma?
Tumor of pancreas
Most common cause of endogenous hyperinsulinemic hypoglycemia in adults
Located anywhere in the pancreas
What are characteristics of congenital hyperinsulinism?
Mutations at the potassium channel
-also can have a dominant gain of function mutation on glucokinase + GDH at the beta cell
GDH – glutamate dehydrogenase
What are the charactistics of GDH-HyperInsulinism?
GLUD1 mutations impair GTP inhibition of GDH
Fasting and post-prandial hypoglycemia
Hyperammonemia
What are the treatment for hyperinsulinemic hypoglycemia?
- diazoxide (activates K channel)
- octreotide (activates K channel)
- surgical
What are the characteristics of immune-mediate hypoglycemia?
Antibodies to insulin receptor and insulin
Antibody will act as insulin AGONIST to cause hypoglycemia
-can act as insulin antagonist to result in HYPERglycemia
Disease tends to be self-limited
When you have a defect in counter-regulation, what should you think of for a hypoglycemia differential?
Growth Hormone and Cortisol deficiency
If you measure high insulin and LOW C-peptide, what does that mean?
C-peptide shows ENDOGENOUS insulin production
High insulin + low c-peptide means hypoglycemia is due to EXOgenous insulin rather than endogenous production
What are the characteristics of G6P deficiency?
Clinical: failure to thrive, hepatomegaly
Treatment = frequent glucose, dextrose
Hyperuricemia, hypertriglyceridemia
Defect in gluconeogenesis pathway = no glucose = hypoglycemia lol
What drugs induce hypoglycemia?
- Sulfonylureas
- Salicylate overdose (aspirin?)
- Beta-adrenergic blocking agents
- Pentamidine
What kind of disease can lead to hypoglycemia?
- liver disease
- renal disease
- sepsis
How do you evaluate hypoglycemia?
1. Counter-regulation Look for -insulin and c-peptide -growth hormone -cortisol 2. intermediate metabolites -beta-hydroxybutyrate -FFA, carnitine total and free, acylcarnitine profile -lactate -ammonia 3. Drug levels
DDx is arrived by separating this shit into what two things?
- acidemia
- means it is NOT insulin mediated (high ketone bodies)
- no acidemia
- means it is INSULIN mediated (low ketone bodies
Should you verify the accuracy of the measurement in glucose?
Yes
Before embarking on an extensive quest fo the cause, verify the accuracy of the measurement
What are questions you need to ask when use the fasting system approach to examine the cause of the hypoglycemia?
- is it a failure of counter-regulation?
- is it a defect on glycogenolysis?
- is it a defect on gluconeogenesis?
- is it a defect on ketogenesis?
What is BOHB?
Beta-hydroxybutyrate
