Lecture 9: Hypoglycemia

Question 1

What are characteristics of hypoglycemia?

Answer 1

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

Question 2

What are the hormones that control glucose?

Answer 2

1. insulin
2. glucagon
3. epinephrine
4. cortisol
5. growth hormone

Question 3

What does cortisol do in terms of glucose homeostasis?

Answer 3

1. stimulates gluconeogenesis

Question 4

What does epinephrine do in terms of glucose homeostasis?

Answer 4

Stimulates

i. glycogenolysis
ii. lipolysis
iii. ketogenesis

Question 5

What does growth hormone do in term of glucose homeostasis?

Answer 5

Stimulates Lipolysis

Question 6

What are Whipple’s triad of hypoglycemic symptoms?

Answer 6

1. symptoms of hypoglycemia
2. measured low glucose at time of symptoms
3. correction of symptoms with food or glucose
   Characteristic but non-specific

Question 7

What is the definition of hypoglycemia?

Answer 7

Activation of glucose counterregulatory systems: 50-55 mg/dl

Cognitive dysfunction = 45-50 mg/dl

Question 8

What are the two symptoms of hypoglycemia?

Answer 8

1. 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
2. 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)

Question 9

What is the significance of beta hydroxybutyrate levels?

Answer 9

High Bhydroxybutyrate levels means LOW insulin since insulin inhibits FFA generation (betahydroxybutyrate

Question 10

What is the significance of acetoacetate?

Answer 10

Shows that body is ketotic
Ketone bdies
That means insulin problem most likely

Question 11

What is late dumping syndrome?

Answer 11

Hyperinsulinemic hypoglycemic after gastric surgery

Question 12

What is the most common cause of persistent hypoglycemia in children and adults?

Answer 12

Hyperinsulemic hypoglycemia

Question 13

What is the diagnostic criteria in hyperinsulinemic hypoglycemia?

Answer 13

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

Question 14

What is an insulinoma?

Answer 14

Tumor of pancreas
Most common cause of endogenous hyperinsulinemic hypoglycemia in adults
Located anywhere in the pancreas

Question 15

What are characteristics of congenital hyperinsulinism?

Answer 15

Mutations at the potassium channel
-also can have a dominant gain of function mutation on glucokinase + GDH at the beta cell
GDH – glutamate dehydrogenase

Question 16

What are the charactistics of GDH-HyperInsulinism?

Answer 16

GLUD1 mutations impair GTP inhibition of GDH
Fasting and post-prandial hypoglycemia
Hyperammonemia

Question 17

What are the treatment for hyperinsulinemic hypoglycemia?

Answer 17

1. diazoxide (activates K channel)
2. octreotide (activates K channel)
3. surgical

Question 18

What are the characteristics of immune-mediate hypoglycemia?

Answer 18

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

Question 19

When you have a defect in counter-regulation, what should you think of for a hypoglycemia differential?

Answer 19

Growth Hormone and Cortisol deficiency

Question 20

If you measure high insulin and LOW C-peptide, what does that mean?

Answer 20

C-peptide shows ENDOGENOUS insulin production

High insulin + low c-peptide means hypoglycemia is due to EXOgenous insulin rather than endogenous production

Question 21

What are the characteristics of G6P deficiency?

Answer 21

Clinical: failure to thrive, hepatomegaly
Treatment = frequent glucose, dextrose
Hyperuricemia, hypertriglyceridemia
Defect in gluconeogenesis pathway = no glucose = hypoglycemia lol

Question 22

What drugs induce hypoglycemia?

Answer 22

1. Sulfonylureas
2. Salicylate overdose (aspirin?)
3. Beta-adrenergic blocking agents
4. Pentamidine

Question 23

What kind of disease can lead to hypoglycemia?

Answer 23

1. liver disease
2. renal disease
3. sepsis

Question 24

How do you evaluate hypoglycemia?

Answer 24

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

Question 25

DDx is arrived by separating this shit into what two things?

Answer 25

1. acidemia
   
   • means it is NOT insulin mediated (high ketone bodies)
2. no acidemia
   
   • means it is INSULIN mediated (low ketone bodies

Question 26

Should you verify the accuracy of the measurement in glucose?

Answer 26

Yes

Before embarking on an extensive quest fo the cause, verify the accuracy of the measurement

Question 27

What are questions you need to ask when use the fasting system approach to examine the cause of the hypoglycemia?

Answer 27

• 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?

Question 28

What is BOHB?

Answer 28

Beta-hydroxybutyrate