182 - Hypoglycemic Disorders

Question 1

What is the definition of hypoglycemia in people with diabetes?

Answer 1

below 70 mg/dL

Question 2

What are the major causes of hypoglycemia?

Answer 2

• 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

Question 3

What is Whipple’s triad?

Answer 3

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

Question 4

What is the importance of glucose levels and brain function?

Answer 4

glucose is the only energy supply for the brain, so if glucose levels drop the brain does not have enough energy to function

Question 5

How are plasma glucose levels maintained between meals/during fasting?

Answer 5

endogenous glucose production, hepatic glycogenolysis, hepatic gluconeogenesis

Question 6

What conditions are required for gluconeogenesis?

Answer 6

low insulin levels

anti-insulin (counterregulatory) hormones

supply of precursors from muscle and adipose tissue to the liver

Question 7

What are the major precursors for gluconeogenesis? Where do they come from?

Answer 7

muscle: lactate, pyruvate, alanine, glutamine (and other amino acids)

adipose tissue: glycerol (from triglycerides)

Question 8

What are the components of the first defenses against hypoglycemia?

Answer 8

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

Question 9

What are the second and third line defenses against hypoglycemia?

Answer 9

second: glucagon stimulation (stimulates hepatic glycogenolysis)
third: epinephrine release stimulates hepatic glycogenolysis and gluconeogenesis (becomes more important with glucagon deficiency

Question 10

What are the major symptoms of hypoglycemia?

Answer 10

diaphoresis, pallor, increased systolic BP and HR, CNS symptoms (behavioral changes, confusion/fatigue, seizure, loss of consciousness, death)

Question 11

What diabetes treatments carry the highest risk for hypoglycemia?

Answer 11

insulin secretagogue (sulfonylureas, glinides) or insulin

common in multiple injection therapies or with insulin pumps

Question 12

How does defective glucose counterregulation impact the defenses against hypoglycemia?

Answer 12

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)

Question 13

What is hypoglycemia unawareness?

Answer 13

attenuaged sympatho-adrenal response affects behavioral response to hypoglycemia and can mask symptoms

Question 14

What are major risk factors for hypoglycemia in diabetes?

Answer 14

• lack of normal epinephrine response
• hypoglycemia unawareness
• absolute insulin deficiency
• history of severe hypoglycemia or hypoglycemia unawareness
• lower HbA1c levels

Question 15

What drugs can cause hypoglycemia?

Answer 15

insulin and secretagogues

ethanol (blocks gluconeogenesis but not glycogenolysis)

ACEs and ARBs

beta blockers

quinolone antibiotics

indomethacin

quinine

sulfonamides

Question 16

What causes of hypoglycemia are associated with critical illness?

Answer 16

renal failure, hepatic failure, cardiac failure, sepsis, starvation

Question 17

What hormone deficiencies can cause hypoglycemia?

Answer 17

addison’s disease and hypopituitarism (glycogen depletion)

cortisol deficiency (impaired gluconeogenesis)

growth hormone deficiency

Question 18

What is the pathophysiology of endogenous hyperinsulinism?

Answer 18

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

Question 19

What are insulinomas?

Answer 19

usually benign, rare insulin secreting tumors that can cause hypoglycemia

Question 20

What hormones are measured to evaluate for insulinomas?

Answer 20

plasma insulin, C-peptide, proinsulin, plasma glucose

all measured during hypoglycemia

Question 21

What imaging studies are used for insulinomas?

Answer 21

CT or MRI

endoscopic ultrasound

pancreatic arterial calcium injection has highest sensitivity, but not used often because it’s invasive

Question 22

What are the treatments for insulinomas?

Answer 22

surgical resection is curative

can also treat with diazoxide (inhibits insulin secretion), octreotide (somatostatin analogue), everolimus (mTOR inhibitor)

Question 23

What condition causes post-prandial hypoglycemia?

Answer 23

post-gastric bypass hypoglycemia

possibly caused by exaggerated GLP-1 response to meals causing hyperinsulinemia and hypoglycemia

Question 24

What is the treatment for post-gastric bypass hypoglycemia?

Answer 24

alpha-glucosidase inhibitor, octreotide

Question 25

How is accidental, surreptitious, or malicious hypoglycemia diagnosed?

Answer 25

hypoglycemia with high C-peptide levels for sulfonylurea ingestion

hypoglycemia with low C-peptide levels for surreptitious or accidental insulin administration

Question 26

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

Answer 26

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

Question 27

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

Answer 27

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