Hypoglycemia Flashcards
T/F Hypoglycemia is a diagnosis
F –> sign
Stored glycogen is depleted in the adult after _____ hours of fasting
24-36
In the first few hours of fasting, the main source of glucose comes from ____
glycogenolysis (and a little bit of gluconeogenesis)
Does the quantity of the hormone increase or decrease during fasting? GH
Growth hormone increases
Does the quantity of the hormone increase or decrease during fasting? ACTH
increases
Does the quantity of the hormone increase or decrease during fasting? cortisol
increases
Does the quantity of the hormone increase or decrease during fasting? Epinephrine
increases
Does the quantity of the hormone increase or decrease during fasting? Insulin
decreases
Does the quantity of the hormone increase or decrease during fasting? glucagon
increases
Which 2 hormones upregulate glycogenolysis?
glucagon and epinephrine
Which 2 hormones upregulate gluconeogenesis?
glucagon and cortisol
Which 2 hormones upregulate lipolysis?
epinephrine and growth hormone
Which hormone upregulates ketogenesis?
epinephrine
Decrease in insulin is accompanied by increase/decrease in free fatty acids and ketone bodies.
increase
Ketone bodies (2)
beta hydroxybutyrate and acetoacetate
What is therapeutic hypoglycemia?
the point at which body starts responding to low glucose –> 65-70 mg/dL
What is diagnostic hypoglycemia?
the point at which symptoms of hypoglycemia reveal themselves –> 50-55 mg/dL
At what glucose level does cognitive dysfunction begin?
45-50 mg/dL
Whipple’s Triad
Required for diagnosis of hypoglycemia: symptoms of hypoglycemia, measured low glucose at time of symptoms, correction of symptoms with food or glucose
Neurogenic symptoms of hypoglycemia
CNS sympathetic discharge –> adrenergic (palpitations, tremor, anxiety) and cholinergic (sweating, hunger,paresthesis)
Neuroglycopenic symptoms of hypoglycemia
confusion, dizziness, fatigue, concentration, vision, headache, focal signs, seizures, etc.
What comes first, neurogenic or neuroglycopenic symptoms?
neurogenic
HAAF
hypoglycemia associated autonomic failure: previous episodes of hypoglycemia may reduce response to later episodes
T1d may often lose glucagon producing islet cells and may lose ____ response as well making them vulnerable to hypoglycemia
epinephrine
T/F glucose levels fall in collection tubes not containing glycolysis inhibitors
T –> used by red and white cells –> glucose meters are not accurate –> need rapid processing of plasma glucose
Hypoglycemia occurring 12-72 hours after food deprivation
fasting hypoglycemia
Hypoglycemia occurring in reaction to food consumption and not while fasting
post prandial hypoglycemia –> uncommon
Causes of post-prandial hypoglycemia
late dumping syndrome (after gastric surgery), early diabetes, reactive hypoglycemia/idiopathic, congenital metabolic disorders
Causes of fasting hypoglycemia
hyerpinsulinism, insulinomas, autoimmune hypoglycemia, growth hormone deficiency, cortisol deficiency, congenitally impaired glycogenolysis, gluconeogenesis, and ketogenesis
Most common cause of persistent hypoglycemia in children/adults
insulinomas in adults and congenital hyperinsulinism in children
Dx criteria for hyperinsulinemic hypoglycemia
increased glucose utilization –> hyperinsulinemia, high cpeptide, hypofattyacidemia,hypoketonemia, glycemic response to glucagon –> during hypoglycemia
Insulinoma
typically small, benign (90%), solitary, located in pancreas
Tx of insulinoma
surgical resection
GDH
glutamate dehydrogenase –> breaks down glutamate formed from amino acids –> increases ATP –> K+ channel –> calcium release –> insulin release form beta cells
Somatostatin MOA
inhibit insulin release by affecting calcium and potassium channels in beta cells
Glucokinase mutation in hyperinsulinism
dominant gain of function –> lowers glucose threshold for insulin release
GDH mutation in hyperinsulinism
dominant gain of function of GLUD1 –> impair GTP inhibition of GDH –> lowers protein threshold for insulin release
K+ channel mutation in hyperinsulinism
rec/dominant loss of function of K+atp channel
HNF4A and HNF1A
dominant mutations in transcription factors that present as hypoglycemia early on and then progress to diabetes later in life
Most common and severe form of congenital hyperinsulinism
Katp –> mutations of SUR1 or Kir6.2
T/F Katp hyperinsulinism is unresponsive to diazoxide
T
T/F Katp hyperinsulinism may be focal or diffuse
T
Classical features of GDH hyperinsulinemia
fasting/post prandial hypoglycemia + hyperammonemia (GLUD1 is also in kidney)
T/F GDH hyperinsulinemia is diazoxide responsive
T
Side effects of diazoxide
fluid retention, hypertichosis
Octreotide MOA
activates Katp channel, affects intracellular translocation of Ca, direct inhibition of insulin secretion
Side effects of octreotide
suppression of GH, TSH, ACTH, GI side effects, necrotizing entercolitis
Immune mediated hypoglycemia
antibodies to insulin receptor –> act as insulin agonist or against insulin itself to cause hypoglycemia (or antagonist to cause hyperglycemia) –> self limited and tx usually unsuccessful
GH/Cortisol deficiency-mediated hypoglycemia
shorten fasting (partial impairment of gluconeogenx and lipolysis)
Tx of GH/Cortisol deficiency-mediated hypoglycemia
replacement of deficient hormones
Clinical clues of GH/Cortisol deficiency-mediated hypoglycemia
midline defect, microphallus, cholestatic liver disease
G6PD
converts G6P to glucose –> hypoglycemia if G6PD –> complete dependence on exogenous glucose –> failure to thrive, hepatomegaly
Lab features of G6PD
hyperlacticacidemia, hypertriglyceridemia, hyperuricemia, lack of glycemic response to fed glucagon stim test
Two types of G6PD
GSD 1a (90%) and 1b
Tx of G6PD
constant feeding
How do G6PD patients survive during fasting
production of ketones
F16PD
converts F16P–>F6P…glucose –> attacks of acidemia, hyperuricemia, hyperlacticacidemia
T/F glycogenolysis is intact in F16PD
T –> longer fasting tolerance than G6PD
T/F gluconeogenesis is intact in F16PD
F –> hypoglycemia with fasting or with fructose consumption (can’t convert it)
Tx of F16PD
limit fasting and no fructose/sucrose
Debrancher deficiency/GSD type 3
can’t break down glycogen –> failure to thrive, hepatomegaly, weakness of muscle
Key feature of debrancher deficiency
hyperketonemia and elevated AST/ALT
Tx of debrancher deficiency
frequent low CHO feeds
T/F cardiomyopathy is not a late consequence of debrancher deficiency
F
MCAD deficiency
cannot break down acyl-coA chains –> hypoketotic hypoglycemia
key feature of MCAD deficiency
elevated LFT/NH3
Tx of MCAD deficiency
limit fasting
Screening for MCAD deficiency
newborn screening by MS acyl-carnitine
Drugs causing hypoglycemia
sulfonylurea, salicylate overdose, beta adrenergic blockers, pentamidine (pneumocystis)
MOA beta adrenergic blocking agents and hypoglycemia
impaired lipolysis –> hypoketotic hypoglycemia
Alcohol induced hypoglycemia
oxidation of ethanol –> NADH –> inhibition of enzymes in gluconeogenesis –>only occurs if hepatic glycogen stores are depleted
Non-islet cell tumors
mesenchymal (retroperitoneal/thoracic sarcomas, fibromas, mesotheliomas, hemangiopericytomas), epithelial (hepatoma, renal cell carcinoma, nonislet cell tumor of pancreas, carcinoid), leukemia/lymphoma
etiology of tumor hypoglycemia
poor nutrition with advanced malignancy, tumor consumption of glucose, reduced hepatic gluconeogenesis/tumor production of insulin like factors, metastatic disease of liver
T/F sepsis can cause hypoglycemia
T
Diff Dx: hypoglycemia with acidemia and high lactate
gluconeogenic defect, alcohol induced
Diff Dx: hypoglycemia with acidemia and low lactate
glycogenolysis or counterregulation defect
Diff Dx: hypoglycemia with high fatty acids
FAO defect
Diff Dx: hypoglycemia with low FFA, low ketones, no acidemia
hyperinsulinemic hypoglycemia
Key feature of insulin-mediate hypoglycemia
suppressed ketones
