Hypoglycemia

Question 0

Which organ is most dependent on glucose?

Answer 0

The brain.

Question 1

Is hypoglycemia a diagnosis?

Answer 1

No it’s a sign. You need to correct the glucose, then determine and correct the underlying problem.

Question 2

About how long does liver glycogen last in an average fasting adult?

Answer 2

24-36 hours

Question 3

3 sources of glucose?

Answer 3

Intake
Glycogenolysis
Gluconeogenesis

Question 4

4 hormones acting directly on effector organs during fasting?

Answer 4

Glucagon
Epinephrine
Cortisol
Growth Hormone

Question 5

Which processes for fasting adaptation does glucagon increase?

Answer 5

Glycogenolysis

Gluconeogenesis

Question 6

Which processes for fasting adaptation does epinephrine increase?

Answer 6

Glycogenolysis
Lipolysis
Ketogenesis

Question 7

Which process for fasting adaptation does cortisol increase?

Answer 7

Gluconeogenesis

Question 8

Which process for fasting adaptation does growth hormone increase?

Answer 8

Lipolysis

Question 9

Blood glucose cutoffs for…
Activation of counterregulatory processes?
Symptoms of hypoglycemia?
Cognitive dysfunction?

Answer 9

Counter-regulation at 65-70mg/dL.
Symptoms at 50-55 mg/dL.
Cognitive dysfunction at 45-50 mg/dL.

Question 10

Diagnostic and therapeutic thresholds for hypoglycemia?

Answer 10

< 50 mg/dL is diagnostic.

< 70 mg/dL merits therapy. (I think that’s what the slide says)

Question 11

What 3 things compose Whipple’s Triad for hypoglycemia? Why is it important to satisfy them?

Answer 11

Symptoms of hypoglycemia.
Measured low blood glucose at time of symptoms.
Correction of symptoms with food/glucose.
Important to satisfy these because the symptoms of hypoglycemia are non-specific.

Question 12

What are neurogenic vs. neuroglycopenic symptoms of hypoglycemia?

Answer 12

Neurogenic: Autonomic (cholinergic and adrenergic) responses to low glucose -palpitations, sweating, hunger, tremor, etc.
Neuroglycopenic: Brain stops working - headache, blurry vision, focal deficients, seizure, etc.

Question 13

What’s one reason why people can progress to neuroglycopenic symptoms without much warning?

Answer 13

Frequent hypoglycemia can blunt the autonomic responses to hypoglycemia - so there’s less warning.
This is called Hypoglycemia-associated Autonomic Failure (HAAF).

Question 14

Why must you rapidly process blood samples collected for glucose levels?

Answer 14

RBCs in there will use it up.

Question 15

2 clinical types of hypoglycemia?

Answer 15

Fasting hypoglycemia: 12-72hrs without food.

Post-prandial hypoglycemia. (uncommon)

Question 16

4 causes of post-prandial hypoglycemia?

Answer 16

Early Dumping Syndrome - in gastric bypass surgery, way food hits gut can cause insulin overreaction.
Early diabetes - dysregulated insulin.
Congenital metabolic disorders - eg. fructose intolerance.
Idiopathic

Question 17

3 types of fasting hypoglycemia?

Answer 17

Insulin-mediated.
Failure of counter-regulation.
Defect in glucose/ketone production.

Question 18

What’s the most common cause of hyperinsulinemic hypoglycemia in adults? In children?

Answer 18

Adults: Insulinoma. (I’m surprised it’s not overdose on insulin… maybe that’s not included)
Children: Congenital hyperinsulinism.

Question 19

What happens if you give glucagon in hyperinsulinemic hypoglycemia? How does this contrast with other hypoglycemias?

Answer 19

Blood glucose will rise, because liver glycogen is not depleted.
In other hypoglycemias, glycogen is depleted.

Question 20

Review: What do you measure to determine endogenous insulin production?

Answer 20

C-peptide.

Question 21

If you have too much insulin, what’s the big picture effect on various energy sources in the blood?

Answer 21

There’s no evidence of trying to compensate for low blood sugar:
Glucose low, fatty acids low, ketones low.

Question 22

Proinsulin levels when there’s an insulinoma?

Answer 22

Are increased.

Question 23

Treatment for insulinoma?

Answer 23

Surgical removal.

Question 24

What's the most common and severe mutation causing congenital hyperinsulinism? What is the function of this gene/protein normally? Responsiveness to drugs?

Answer 24

Loss of function mutations in the ATP-inhibited (that's my term...) K+ channel of beta calls (SUR or Kir6.2 are the real terms). Normally, when beta cells are trying to make insulin, ATP is increased, which inhibits this K+ channel, leading to insulin secretion. This mutation is not diazoxide-responsive.

Question 25

What are the 2 most important drugs used in congenital hyperinsulinism? How do they work? (there's a 3rd one mentioned as well...)

Answer 25

Diazoxide: Keeps the ATP-inhibited K+ channel of beta cells open. Somatostatin (analogues): Inhibit Ca++ influx that causes secretory vesicle release. -Octreotide: Activates ATP-inhibited K+ channel, acts on Ca++ signaling (has more/worse side effects).

Question 26

What do GLUD1 mutations do? Why does that matter? | Treatment for it?

Answer 26

Mutations in GLUD1 impair the ability of GTP to inhibit glutamate dehydrogenase (GDH). Overactive GDH makes too much ATP in beta cells -> inhibition of ATP-inhibited K+ channel -> hyperinsulinemia. (also causes hyperammonemia) Treatment = diazoxide to keep the K+ channel open.

Question 27

2 different forms of immune-mediated hypoglycemia?

Answer 27

Agonist antibodies to insulin receptor. | Anti-insulin antibodies, which can sequester insulin and then release it suddenly in boluses.

Question 28

What are the take-home points about hypoglycemia caused by cortisol and growth hormone deficiencies?

Answer 28

It's more mild, manifests as ketosis during fasting, can be seen by other symptoms/signs of the deficiency, treated with hormone-replacement.

Question 29

3 processes that when disrupted by inborn errors of metabolism can cause hypoglycemia?

Answer 29

Glycogenolysis Gluconeogenesis Fatty Acid Oxidation / Ketogenesis

Question 30

What processes are messed up by glucose-6-phosphatase deficiency? What remains intact? Treatment?

Answer 30

Liver can't release glucose, so both gluconeogenesis and glycogenolysis are messed up. Ketone production remains intact. Treatment is for patients to never fast.

Question 31

What happens in Fructose-1,6-diphosphatase deficiency? What happens during fasting? Treatment?

Answer 31

Can't "run glycolysis in reverse"-ish for gluconeogenesis. Fasting -> lactic acidemia. Fructose intolerant. Treatment is to not fast, avoid fructose.

Question 32

Most common glycogenolysis defect? Treatment? Long term effects?

Answer 32

GSD-3 (debrancher) Treatment: No fasting. Low carb, high protein diet. Long term complications: Cardiomyopathy and myopathy.

Question 33

Effects of Medium-Chain Acyl-CoA Dehydrogenase deficiency?

Answer 33

Impaired ketone production - problems when fasting > 12 hrs.

Question 34

4 common drugs other than insulin that hypoglycemia?

Answer 34

Sulfonylurea. Salicylate overdose (esp in children). Beta blockers - can produce adrenergic response to hypoglycemia. Pentamidine (for P. carinii) - destroys beta cells.

Question 35

How can EtOH cause hypoglycemia? What makes this more likely to happen?

Answer 35

EtOH metabolism produces lots of NADH, which turns off gluconeogenesis. Happens more in children, people on oral glucose-lowering agents, having fasted before EtOH consumption.

Question 36

How can tumors cause hypoglycemia?

Answer 36

Lots of different ways... consuming glucose, impairing liver function, impairing nutrition.

Question 37

How can renal disease contribute to hypoglycemia?

Answer 37

Loss of protein in urine - less substrate for gluconeogenesis. Kidney itself does this gluconeogenesis. Reduced extraction of insulin.

Question 38

3 categories of things to measure when working up hypoglycemia?

Answer 38

Counter-regulation - (Insulin, C-peptide, GH, cortisol). Intermediate metabolites - (beta-hydroxybutyrate, FFAs, lactate, ammonia, etc.). Other stuff - drug levels.

Question 39

Evaluating hypoglycemia involves...

Answer 39

Fasting until glucose < 50mg/dL, taking blood periodically. | Glucagon test.

Question 40

2 things that can cause acidotic, high-lactate hypoglycemia?

Answer 40

Gluconeogenic defect. | Alcohol-induced.

Question 41

2 cause of hypoglycemia with acidemia and high ketones?

Answer 41

Defect in glycogenolysis. | Defect in counter-regulation.

Question 42

Cause of hypoglycemia without acidemia, with low ketones, high FFAs?

Answer 42

Fatty acid oxidation defects (can't make ketones).

Question 43

Cause of hypoglycemia without acidemia, with low ketones, and low FFAs?

Answer 43

Hyperinsulinemia (no signs of trying to compensate for low glucose)