182 - Hypoglycemic Disorders Flashcards
What is the definition of hypoglycemia in people with diabetes?
below 70 mg/dL
What are the major causes of hypoglycemia?
- drugs for treating diabetes mellitus
- exposure to drugs (including alcohol)
other causes: organ failure, sepsis, hormone deficiencies, non-beta-cell tumors, prior gastric bypass surgery
What is Whipple’s triad?
triad of symptoms of hypoglycemia:
1) symptoms consistent with hypoglycemia (altered consciousness, seizures, etc.)
2) low plasma glucose concentration measured with a precise method
3) relief of those symptoms after plasma glucose level is raised
What is the importance of glucose levels and brain function?
glucose is the only energy supply for the brain, so if glucose levels drop the brain does not have enough energy to function
How are plasma glucose levels maintained between meals/during fasting?
endogenous glucose production, hepatic glycogenolysis, hepatic gluconeogenesis
What conditions are required for gluconeogenesis?
low insulin levels
anti-insulin (counterregulatory) hormones
supply of precursors from muscle and adipose tissue to the liver
What are the major precursors for gluconeogenesis? Where do they come from?
muscle: lactate, pyruvate, alanine, glutamine (and other amino acids)
adipose tissue: glycerol (from triglycerides)
What are the components of the first defenses against hypoglycemia?
1) pancreatic beta-cell insulin secretion decreases
2) hepatic glycogenolysis and hepatic (and renal) gluconeogenesis increases
3) glucose utilization in peripheral tissues is reduced (due to low insulin levels)
4) lipolysis and proteolysis are increased to release gluconeogenic precursors
5) glucose counterregulatory hormones are released
What are the second and third line defenses against hypoglycemia?
second: glucagon stimulation (stimulates hepatic glycogenolysis)
third: epinephrine release stimulates hepatic glycogenolysis and gluconeogenesis (becomes more important with glucagon deficiency
What are the major symptoms of hypoglycemia?
diaphoresis, pallor, increased systolic BP and HR, CNS symptoms (behavioral changes, confusion/fatigue, seizure, loss of consciousness, death)
What diabetes treatments carry the highest risk for hypoglycemia?
insulin secretagogue (sulfonylureas, glinides) or insulin
common in multiple injection therapies or with insulin pumps
How does defective glucose counterregulation impact the defenses against hypoglycemia?
in the setting of endogenous insulin deficiency, insulin levels do not decrease as plasma glucose levels fall (first defense gone)
glucagon levels do not increase as plasma glucose levels fall further (second defense gone)
epinpehrine secretion is attenuated in response to hypoglycemia (third defense reduced)
What is hypoglycemia unawareness?
attenuaged sympatho-adrenal response affects behavioral response to hypoglycemia and can mask symptoms
What are major risk factors for hypoglycemia in diabetes?
- lack of normal epinephrine response
- hypoglycemia unawareness
- absolute insulin deficiency
- history of severe hypoglycemia or hypoglycemia unawareness
- lower HbA1c levels
What drugs can cause hypoglycemia?
insulin and secretagogues
ethanol (blocks gluconeogenesis but not glycogenolysis)
ACEs and ARBs
beta blockers
quinolone antibiotics
indomethacin
quinine
sulfonamides
What causes of hypoglycemia are associated with critical illness?
renal failure, hepatic failure, cardiac failure, sepsis, starvation
What hormone deficiencies can cause hypoglycemia?
addison’s disease and hypopituitarism (glycogen depletion)
cortisol deficiency (impaired gluconeogenesis)
growth hormone deficiency
What is the pathophysiology of endogenous hyperinsulinism?
failure of insulin secretion to fall to very low levels during hypoglycemia
caused by beta-cell tumors, beta-cell disorders/hypertrophy, antibodies to insulin or receptor, beta-cell secretagogues, post-gastric bypass
What are insulinomas?
usually benign, rare insulin secreting tumors that can cause hypoglycemia
What hormones are measured to evaluate for insulinomas?
plasma insulin, C-peptide, proinsulin, plasma glucose
all measured during hypoglycemia
What imaging studies are used for insulinomas?
CT or MRI
endoscopic ultrasound
pancreatic arterial calcium injection has highest sensitivity, but not used often because it’s invasive
What are the treatments for insulinomas?
surgical resection is curative
can also treat with diazoxide (inhibits insulin secretion), octreotide (somatostatin analogue), everolimus (mTOR inhibitor)
What condition causes post-prandial hypoglycemia?
post-gastric bypass hypoglycemia
possibly caused by exaggerated GLP-1 response to meals causing hyperinsulinemia and hypoglycemia
What is the treatment for post-gastric bypass hypoglycemia?
alpha-glucosidase inhibitor, octreotide
How is accidental, surreptitious, or malicious hypoglycemia diagnosed?
hypoglycemia with high C-peptide levels for sulfonylurea ingestion
hypoglycemia with low C-peptide levels for surreptitious or accidental insulin administration
A 39 yo complains of hypoglycemic episodes day and night. She reports the need to eat frequently, every 2-3 hours and in the middle of the night and has experienced a 20 lb. weight gain in the last 6 months. Family members report she at times “acts funny,” seems disoriented and gets back to normal after eating. What is the most likely cause of his hypoglycemia?
a) starvation
b) surreptitious intake of insulin
c) insulinoma
d) binge alcohol consumption
e) sulfonylurea intake
c) insulinoma
insulinomas cause hypoglycemia, especially fasting, usually patients need to eat very often, including during the night, with subsequent weight gain; also they experience glyconeuropenic symptoms (disorientation, confusion), that are easily relieved by ingestion of carbohydrates
A 79 yo man with type II diabetes for 30 years, has recently developed seizures. He states that he has been taking all his medications regularly, including his mealtime insulin doses, however at times he forgets to eat. Which of the following is the most likely cause of his seizures?
a) insulin
b) brain tumor
c) insulinoma
d) binge alcohol consumption
e) starvation
a) insulin
patient has been forgetting to eat his meals despite taking insulin doses regularly, leading to hypoglycemia induced by insulin in the absence of food intake; about 70% of patients with diabetes on multiple daily insulin injection experience hypoglycemia
