Hypoglycemia Flashcards
Which organ is most dependent on glucose?
The brain.
Is hypoglycemia a diagnosis?
No it’s a sign. You need to correct the glucose, then determine and correct the underlying problem.
About how long does liver glycogen last in an average fasting adult?
24-36 hours
3 sources of glucose?
Intake
Glycogenolysis
Gluconeogenesis
4 hormones acting directly on effector organs during fasting?
Glucagon
Epinephrine
Cortisol
Growth Hormone
Which processes for fasting adaptation does glucagon increase?
Glycogenolysis
Gluconeogenesis
Which processes for fasting adaptation does epinephrine increase?
Glycogenolysis
Lipolysis
Ketogenesis
Which process for fasting adaptation does cortisol increase?
Gluconeogenesis
Which process for fasting adaptation does growth hormone increase?
Lipolysis
Blood glucose cutoffs for…
Activation of counterregulatory processes?
Symptoms of hypoglycemia?
Cognitive dysfunction?
Counter-regulation at 65-70mg/dL.
Symptoms at 50-55 mg/dL.
Cognitive dysfunction at 45-50 mg/dL.
Diagnostic and therapeutic thresholds for hypoglycemia?
< 50 mg/dL is diagnostic.
< 70 mg/dL merits therapy. (I think that’s what the slide says)
What 3 things compose Whipple’s Triad for hypoglycemia? Why is it important to satisfy them?
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.
What are neurogenic vs. neuroglycopenic symptoms of hypoglycemia?
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.
What’s one reason why people can progress to neuroglycopenic symptoms without much warning?
Frequent hypoglycemia can blunt the autonomic responses to hypoglycemia - so there’s less warning.
This is called Hypoglycemia-associated Autonomic Failure (HAAF).
Why must you rapidly process blood samples collected for glucose levels?
RBCs in there will use it up.
2 clinical types of hypoglycemia?
Fasting hypoglycemia: 12-72hrs without food.
Post-prandial hypoglycemia. (uncommon)
4 causes of post-prandial hypoglycemia?
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
3 types of fasting hypoglycemia?
Insulin-mediated.
Failure of counter-regulation.
Defect in glucose/ketone production.
What’s the most common cause of hyperinsulinemic hypoglycemia in adults? In children?
Adults: Insulinoma. (I’m surprised it’s not overdose on insulin… maybe that’s not included)
Children: Congenital hyperinsulinism.
What happens if you give glucagon in hyperinsulinemic hypoglycemia? How does this contrast with other hypoglycemias?
Blood glucose will rise, because liver glycogen is not depleted.
In other hypoglycemias, glycogen is depleted.
Review: What do you measure to determine endogenous insulin production?
C-peptide.
If you have too much insulin, what’s the big picture effect on various energy sources in the blood?
There’s no evidence of trying to compensate for low blood sugar:
Glucose low, fatty acids low, ketones low.
Proinsulin levels when there’s an insulinoma?
Are increased.
Treatment for insulinoma?
Surgical removal.
What’s the most common and severe mutation causing congenital hyperinsulinism? What is the function of this gene/protein normally? Responsiveness to drugs?
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.
What are the 2 most important drugs used in congenital hyperinsulinism? How do they work?
(there’s a 3rd one mentioned as well…)
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).
What do GLUD1 mutations do? Why does that matter?
Treatment for it?
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.
2 different forms of immune-mediated hypoglycemia?
Agonist antibodies to insulin receptor.
Anti-insulin antibodies, which can sequester insulin and then release it suddenly in boluses.
What are the take-home points about hypoglycemia caused by cortisol and growth hormone deficiencies?
It’s more mild, manifests as ketosis during fasting, can be seen by other symptoms/signs of the deficiency, treated with hormone-replacement.
3 processes that when disrupted by inborn errors of metabolism can cause hypoglycemia?
Glycogenolysis
Gluconeogenesis
Fatty Acid Oxidation / Ketogenesis
What processes are messed up by glucose-6-phosphatase deficiency? What remains intact? Treatment?
Liver can’t release glucose, so both gluconeogenesis and glycogenolysis are messed up. Ketone production remains intact.
Treatment is for patients to never fast.
What happens in Fructose-1,6-diphosphatase deficiency?
What happens during fasting?
Treatment?
Can’t “run glycolysis in reverse”-ish for gluconeogenesis.
Fasting -> lactic acidemia. Fructose intolerant.
Treatment is to not fast, avoid fructose.
Most common glycogenolysis defect? Treatment? Long term effects?
GSD-3 (debrancher)
Treatment: No fasting. Low carb, high protein diet.
Long term complications: Cardiomyopathy and myopathy.
Effects of Medium-Chain Acyl-CoA Dehydrogenase deficiency?
Impaired ketone production - problems when fasting > 12 hrs.
4 common drugs other than insulin that hypoglycemia?
Sulfonylurea.
Salicylate overdose (esp in children).
Beta blockers - can produce adrenergic response to hypoglycemia.
Pentamidine (for P. carinii) - destroys beta cells.
How can EtOH cause hypoglycemia? What makes this more likely to happen?
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.
How can tumors cause hypoglycemia?
Lots of different ways… consuming glucose, impairing liver function, impairing nutrition.
How can renal disease contribute to hypoglycemia?
Loss of protein in urine - less substrate for gluconeogenesis.
Kidney itself does this gluconeogenesis.
Reduced extraction of insulin.
3 categories of things to measure when working up hypoglycemia?
Counter-regulation - (Insulin, C-peptide, GH, cortisol).
Intermediate metabolites - (beta-hydroxybutyrate, FFAs, lactate, ammonia, etc.).
Other stuff - drug levels.
Evaluating hypoglycemia involves…
Fasting until glucose < 50mg/dL, taking blood periodically.
Glucagon test.
2 things that can cause acidotic, high-lactate hypoglycemia?
Gluconeogenic defect.
Alcohol-induced.
2 cause of hypoglycemia with acidemia and high ketones?
Defect in glycogenolysis.
Defect in counter-regulation.
Cause of hypoglycemia without acidemia, with low ketones, high FFAs?
Fatty acid oxidation defects (can’t make ketones).
Cause of hypoglycemia without acidemia, with low ketones, and low FFAs?
Hyperinsulinemia (no signs of trying to compensate for low glucose)
