SM_182b: Hypoglycemia and Other Islet Issues

Question 1

In people with diabetes, hypoglycemia is ____

Answer 1

In people with diabetes, hypoglycemia is plasma glucose < 70 mg/dL

• Should be considered in any patient with episodes of confusion, altered level of consciousness, or seizure
• Usually medical emergency

Question 2

Severe hypoglycemia is ____

Answer 2

Severe hypoglycemia is requiring assistance of others for carbohydrates, glucagon, or to take action

• Neurological recovery following return of plasma to normal is sufficient evidence the event was induced by low plasma glucose

Question 3

Documented symptomatic hypoglucemia is ___

Answer 3

Documented symptomatic hypoglucemia is event when typical symptoms of hypoglycemia are accompanied by blood glucose of < 70 mg/dL

Question 4

Asymptomatic hypoglycemia is ____

Answer 4

Asymptomatic hypoglycemia is event not accompanied by typical symptoms of hypoglycemia but with a blood glucose of < 70 mg/dL

Question 5

Probable symptomatic hypoglycemia is ____

Answer 5

Probable symptomatic hypoglycemia is symptoms of hypoglycemia without a blood glucose but presumably caused by a blood glucose < 70 mg/dL

Question 6

Pseudo-hypoglycemia is ____

Answer 6

Pseudo-hypoglycemia is reporting typical symptoms of hypoglycemia with measured blood glucose > 70 mg/dL but approaching that level (trend of hypoglycemia)

Question 7

Whipple’s triad is ____, ____, and ____

Answer 7

Whipple’s triad is

• Symptoms consistent with hypoglycemia (neuroglycopenic symptoms)
• Low plasma [glucose] measured with a precise method (plasma)
• Relief of those symptoms after plasma glucose level is raised

Question 8

First line of defense is when blood glucose is ____ and involves ____

Answer 8

First line of defense is when blood glucose is 80-85 mg/dL and involves decreased insulin

Question 9

Second line of defense is when blood glucose is ____ and involves ____

Answer 9

Second line of defense is when blood glucose is 65-70 mg/dL and involves increased glucagon

Question 10

Third line of defense is when blood glucose is ____ and involves ____

Answer 10

Third line of defense is when blood glucose is 65-70 mg/dL and involves increased epinephrine

Question 11

Describe systemic glucose balance and glucose counter-regulation

Answer 11

Systemic glucose balance and glucose counter-regulation

• Glucose: obligate metabolic fuel for the brain
• When arterial blood glucose falls, blood-to-brain glucose transport becomes insufficient to support brain energy metabolism and function
• Insulin plays a dominant role among the regulatory factors in glucose homeostasis
• Glucose counter-regulatory mechanisms prevent or rapidly correct hypoglycemia

Question 12

During fasting state, normal blood glucose is ____ with transient higher excursions after a meal

Answer 12

During fasting state, normal blood glucose is 70-100 mg/dL with transient higher excursions after a meal

• Hepatic glycogen stores maintain blood glucose for 8 hours
• Duration changes based on nutrition or illness

Question 13

Between meals and during fasting, plasma glucose levels are maintained by ____, ____, and ____

Answer 13

Between meals and during fasting, plasma glucose levels are maintained by endogenous glucose production, hepatic glycogenolysis, and hepatic and renal gluconeogenesis

Question 14

Describe clinical manifestations of hypoglycemia

Answer 14

Clinical manifestations of hypoglycemia

• Diaphoresis, pallor
• Increased systolic BP and increased HR
• No change if repeated low BG
• Confusion, fatigue, seizure, LOC, death
• Adrenergic symptoms: palpitations, tremor, anxiety
• Cholinergic symptoms: sweating, hunger, paresthesias

Question 15

General causes of hypoglycemia in ill-appearing individuals are ____, ____, ____, and ____

Answer 15

General causes of hypoglycemia in ill-appearing individuals are drugs, critical illness, hormone deficiences, and non-Islet tumors

Question 16

General causes of hypoglycemia in healthy-appearing individuals are ____ and ____

Answer 16

General causes of hypoglycemia in healthy-appearing individuals are endogenous hyperinsulinism and insulin autoimmune hypoglycemia

Question 17

____ is the limiting factor in management of diabetes

Answer 17

Hypoglycemia is the limiting factor in management of diabetes

• Causes recurrent morbidity in T12DM and T2DM

Question 18

___ is a risk factor for hypoglycemia in diabetes

Answer 18

Relative or absolute insulin excess is a risk factor for hypoglycemia in diabetes

• Insulin doses are excessive / poorly timed / wrong type
• Reduced influx of exogenous glucose (fast, missed meals)
• Increased insulin-independent glucose utilization (exercise)
• Increased insulin sensitivity: improved glycemic control, middle of night, late after exercise, increased fitness/ weight loss
• Reduced endogenous glucose production: alcohol ingestion
• Reduced insulin clearance: insulin failure

Question 19

Hypoglycemia associated autonomic failure is ____

Answer 19

Hypoglycemia associated autonomic failure is defective glucose counter-regulation, compromising physiological defense

• Reversible
• Insulin levels do not decrease
• Glucagon levels do not increase
• Epinephrine increase is blunted towards lower blood glucose concentrations
• Absence of adrenergic and cholinergic symptoms that make patients recognize hypoglycemia and ingest carbohydrates
• Caused by aggressive glycemic therapy for diabetes
• Reversible with avoidance of hypoglycemia

Question 20

Hypoglycemia begets _____

Answer 20

Hypoglycemia begets hypoglycemia

Question 21

Describe hypoglycemia-associated autonomic failure

Answer 21

Hypoglycemia-associated autonomic failure

Question 22

Hypoglycemia is ___ in the absence of diabetes

Answer 22

Hypoglycemia is rare in the absence of diabetes

• Hypoglycemic disorder present only when Whipple’s triad can be demonstrated

Question 23

_____, _____, _____, and _____ can cause hypoglycemia without diabetes

Answer 23

Drugs, critical illness, hormone deficiencies, and non-beta cell tumors can cause hypoglycemia without diabetes

• Drugs: insulin / insulin secretagogues, ethanol, ACE-i / ARB, beta-adrenergic receptor antagonists, quinolones, indomethacin, quinine, sulfonamides
• Critical illness: renal failure, hepatic failure, cardiac failure, sepsis, starvation
• Hormone deficiences: Addison’s disease, cortisol deficiency, growth hormone deficiency

Question 24

Ethanol blocks ____ but not ____

Answer 24

Ethanol blocks gluconeogenesis but not glycogenolysis

• Alcohol-induced hypoglycemia occurs after a several day ethanol binge with very little food ingestion and glycogen depletion
• Ethanol levels correlate poorly with plasma glucose concentrations
• Contributes to hypoglycemia for patients on insulin because gluconeogenesis become predominant route of glucose production during prolonged hypoglycemia

Question 25

Non-beta cell tumors cause ___

Answer 25

Non-beta cell tumors cause fasting hypoglycemia

• Occurs in patients with large mesenchymal or epithelial tumors: hepatomas, adrenocortical carcinomas, carcinoids
• Insulin secretion is suppressed appropriately during hypoglycemia

Question 26

People with large mesenchymal or epithelial tumors such as ____, ____, or ____ may have fasting hypoglycemia

Answer 26

People with large mesenchymal or epithelial tumors such as hepatomas, adrencortical carcinomas, and carcinoids may have fasting hypoglycemia

(non-beta cell tumors)

Question 27

Non-beta cell tumors cause hypoglycemia due to ____

Answer 27

Non-beta cell tumors cause hypoglycemia due to overproduction of big IGF-II

• An incompletely processed form of insulin-like growth factor II
• IGF-II does not complex with circulating binding proteins and has faster access to target tissues via insulin receptors

Question 28

Describe diagnosis of non-beta cell tumors

Answer 28

Non beta-cell tumor diagnosis

• Tumors are usually clinically apparent and visualized with CT scans / imaging tests
• Laboratory findings: high plasma IGF-II to IGF-I ratios, high free IGF-II, high levels of pro-IGF-II
• Treat with surgical resection

Question 29

Describe causes of endogenous hyperinsulinism

Answer 29

Endogenous hyperinsulinism causes

• Primary beta-cell disorder, typically insulinoma
• Functional beta-cell disorder with beta-cell hypertrophy or hyperplasia (nesidioblastosis)
• Antibody to insulin / insulin receptor (late postprandial)
• Beta-cell secretagogue (sulfonylurea)
• Post-gastric bypass hypoglycemia (post-prandial hypoglycemia, non-insulinoma pancreatogenous hypoglycemia)

Question 30

____ is a treatable cause of potentially fatal hypoglycemia and can be sporadic or genetically inherited (MEN 1)

Answer 30

Insulinoma is a treatable cause of potentially fatal hypoglycemia and can be sporadic or genetically inherited (MEN 1)

Question 31

Insulinoma pathophysiology involves ____

Answer 31

Insulinoma pathophysiology involves failure of insulin secetion to fall to very low levels during hypoglycemia (tumoral production)

• Almost all in pancreas

Question 32

Insulinoma diagnosis involves measuring hormones during ___

Answer 32

Insulinoma diagnosis involves measuring hormones during hypoglycemia

• Plasma insulin: inappropriately high
• C-peptide: inappropriately high
• Proinsulin: inappropriately high
• Plasma glucose: very low
• Assess symptoms and resolution by IV glucagon

Question 34

These are ____

Answer 34

These are insulinomas

(surgical resection generally curative)

Question 35

Describe post-gastric bypass hypoglycemia

Answer 35

Post-gastric bypass hypoglycemia

• Usually post-prandial
• Endogenous hyperinsulinism, usually after Roux en Y gastric bypass
• Potential mechanism of action: exaggerated GLP-1 responses to meals -> hyperinsulinemia and hypoglycemia

Question 36

Describe accidental, surreptitious, or malicious hypoglycemia

Answer 36

Accidental, surreptitious, or malicious hypoglycemia

• Due to accidental ingestion of an insulin secretagogue (pharmacy / medical error) or insulin
• Surreptitious / maliciious administration of insulin or secretagogue very similar clinically and biochemically to insulinoma
• Most common in healthcare workers, patients with diabetes or relatives, and people with factitious illnesses

Question 37

Describe diagnosis of accidental, surreptitious, or malicious hypoglycemia

Answer 37

Diagnosis of accidental, surreptitious, or malicious hypoglycemia

• High C-peptide levels for sulfonylurea ingestion
• Low C-peptide levels with surreptitious or accidental insulin administration (suppression of insulin secretion)

Question 38

Hypoglycemia from inaccurate glucose measurements is ___

Answer 38

Hypoglycemia from inaccurate glucose measurements is artifactual from continued glucose metabolism by blood elements after blood draw

• Enhanced by leukocytosis, erythrocytosis, thrombocytosis, and delayed separation (pseudohypoglycemia)