Flashcards in Hypoglycemia Deck (56):
What is hypoglycemia
A sign, not a diagnosis. Results when glucose utilization exceeds production
What are the main tissues of glucose use?
Muscle, red and white cells, renal medulla
What are the sources of glucose?
Ingestion, glycogenolysis, gluconeogenesis
How long until glycogen stores are depleted in adult?
After 24-36 hrs of fasting
Where does gluconeogenesis occur?
Liver, renal cortex, from lactate, glycerol and amino acids (alanine in liver, glutamine in renal cortex)
What 3 systems must fail to result in hypoglycemia?
Glycogenolysis, gluconeogenesis, ketogenesis
Hormonal control of insulin
Stops glycogenolysis, gluconeogenesis, lipolysis, ketogenesis
Hormonal control of glucagon
Promotes glycogenolysis, gluconeogenesis
Hormonal control of epinephrine
Promotes glycogenolysis, lipolysis and ketogenesis
Hormonal control of cortisol
Hormonal control of growth hormone
What range of glucose is normal
What is a dec in insulin accompanied by
-inc in free FAs and ketone body generation (beta hydroxybutyrate and acetoacetate)
How much glucose should be in the blood to suppress insulin secretion
How much glucose should be in the blood to increase glucagon release
How much glucose should be in the blood to increase epinephrine release
How much glucose should be in the blood to increase cortisol and growth hormone
How much glucose should be in the blood to be aware of symptoms
How much glucose should be in the blood to impair cognition
What is Whipple's triad?
Must be satisfied to be hypoglycemia
1. Symp and/or signs compatible with hypoglycemia
2. A low measured plasma glucose concentration
3. Resolution of symptoms/signs when glucose concentration is normalized
Symptoms are characteristics, but non-specific
What 2 broad categories of symptoms of hypoglycemia?
Neurogenic and neuroglycopenic
What are the neurologic symptoms of hypoglycemia?
Neurogenic (autonomic): adrenergic (palpitations, tremor, anxiety) and cholinergic (sweating, hunger, paresthesis)
Sympathetic nervous discharged is triggered by hypoglycemia: how the pts become aware of it
What are the neuroglycopenic symptoms of hypoglycemia?
Arise from failure of brain fxn caused by deficient glucose: confusion. dizziness, fatigue, inability to concentrate, blurred vision, headache, focal neurological signs, loss of consciousness, seizures, depression of respiration, death
Which symptoms come first?
NEurogenic precede neuroglycopenic
What is HAAF?
Hypoglycemia associated autonomic failure: hypoglycemia unawareness because prev episodes of hypoglycemia may modify response to a later episode, typically attenuating the adrenergic response
What happens to T1D alpha cells?
T1D pts often lose glucagon-producing islet cells and may lose epinephrine response as well, making them vulnerable to hypoglycemia
What is fasting hypoglycemia?
Occurs 12-72 hours after food deprivation (shorter in individuals with excessive insulin)-->most cases
What is post prandial hypoglycemia/reactive
Occurs in reaction to food consumption and not while fasting-->very uncommon
What are some examples of post-prandial hypoglycemia?
-Late dumping syndrome
-Certain congenital metabolic disorders (galactosemia, hereditary fructose intolerance)
What are possible causes of fasting hypoglycemia?
Failure of counter regulation
Convenital metabolic disorders
What is the most common cause of persistent hypoglycemia?
What is the most common cause of persistent hypoglycemia in adults?
What is the most common cause of persistent hypoglycemia in children?
What is hyperinsulinemic hypoglycemia?
Caused by increased glucose utilization in the presence of too much insulin
Diagnostic criteria for hyperinsulinemic hypoglycemia?
-During the hypoglycemic state, labs will also show: hyperinsulinemia, high C-peptide, dec free fatty acids, hypoketonemia, and a glycemic response to injected glucagon (this is important to know) -> the high insulin suppresses glycogenolysis, so glucagon will induce utilization of stored glycogen
-inc glucose utilization
Treatment of hyperinsulinemic hypoglycemia?
Treatment: diazoxide, which activates the KATP channel to close, and octreotide, which affects intracellular Ca2+, inhibiting insulin secretion.
What are insulinomas?
Most common cause of endogenous hyperinsulinemia in adults. They are benign in over 90% of cases, usually located within the pancreas, and treated with surgery.
What is the diagnosis of insulinomas?
During the hypoglycemic state, labs will also show: elevated insulin, elevated C-peptide, and elevated proinsulin -> the tumor cells don’t process proinsulin properly, so the ratio of circulating insulin to proinsulin will be abnormal
Treatment of insulinomas?
What is congenital hyperinsulinism?
Most common cause of hyperinsulinemia in kids. There are multiple known mutations that result in increased insulin production/release.
What is the normal process that leads to insulin release?
Glucose enters the pancreatic beta cell and is converted to ATP in a pathway involving the glucokinase enzyme. ATP stimulates a K+ channel to close, which depolarizes the beta cell, opening a voltage-dependent Ca2+ channel. The influx of Ca2+ triggers insulin release. Also, the beta cell can convert amino acids (leucine, glutamate) into ATP, using the GDH enzyme, which then follows the same pathway.
Katp Channel Mutation
Loss of function leads to dysregulated insulin release. Can be diffuse throughout the entire pancreas or affect only a fraction of beta cells.
Signs: severe hyperinsulinemia, neonatal onset, large gestational age
Diazoxide unresponsive. This is a drug that targets the K+ channel, stimulating it to remain open. The mutated KATP channel is unaffected by this therapy.
Most common and severe form of congenital HI
GDH-HI (hyperinsulinism/hyperammonemia syndrome)
GDH mutation: leads to the loss of GDH inhibition, meaning the enzyme is always on, creating too much ATP within the beta cell. (activating mutation)
Co-presents with hyperammonemia (enzyme also plays a role in ammonia clearance in kidneys)
Signs: mild, late onset, normal birth weight
Autoimmune: (rare) can be caused by antibodies to the insulin receptor, which act as either agonists (resulting in hypoglycemia) or antagonists (causing hyperglycemia).
Antibodies to insulin can also be present (Hirata's disease), which trap insulin in circulation and then release it at random
Disease is usually self-limited
Treatment: immunosuppression, steroids, plasmapheresis generally unsuccessful
Growth hormone/cortisol deficiency
Failure of counter regulation
Partial impairment of gluconeogenesis and lipolysis, leading to decreased tolerance of fasting.
Will present with hypoglycemia and elevated ketones
Treatment: replace deficient hormones
Congenital metabolic disorder (inborn error of metab)
G6P is necessary to release synthesized glucose from the liver (either from glycogenolysis or ketogenesis). Patients w/ this deficiency can only utilize glucose that they take in from meals, so this is treated with frequent feeding.
Labs: high triglycerides, lactic acid, uric acid, and a lack of glycemic response to a glucagon stimulation test
2 mutations: GSD 1a (90%) and 1b. People with 1b can get neutropenia making them more susceptible to infections
Can't eat lactose/fructose
Prevents production of glucose from lactate in the liver
Get attacks of acidemia, hyperlacticacidemia, hyperuricemia
Triggers: fasting or fructose
Treatment: limit fasting <8-12hrs, no fructose/sucrose
Glycogen debrancher deficiency
Results in accumulation of glycogen in liver and muscle and may lead to liver failure
Clinical: failure to thrive, hepatomegaly, muscle weakness
Labs: hyperketonemia, inc liver enzymes
Can lead to cardiomyopathy and myopathy because can't break down glycogen
Medium-Chain Acyl-CoA Dehydrogenase Definiency
-Screen in new borns
-Limit fasting <12 hrs
What drugs cause hypoglycemia?
Beta adrenergic blocking agents
Alcohol induced hypoglycemia
Common in T1D, oxidation of ethanol to acetic acid generates NADH, which can inhibit several gluconeogenic enzymes including conversion of lactate and AAs to pyruvate
Presents with hypoglycemia ~6-36 hours after eating
Non-islet cell tumors
Present sign or herald recurrence of tumor
Mesenchymal, epithelial or leukemia and lymphoma
Etiology of tumor hypoglycemia
Poor nutrition with advanced malignancy, tumor consumes glucose, reduced hepatic gluconeogenesis, metastatic disease involving the liver
Hepatic and renal disease
Can disrupt gluconeogenesis or cause substrate deprivation (like muscle wasting due to renal dis)
Can also cause hypoglycemia