SM_182b: Hypoglycemia and Other Islet Issues Flashcards
In people with diabetes, hypoglycemia is ____
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
Severe hypoglycemia is ____
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
Documented symptomatic hypoglucemia is ___
Documented symptomatic hypoglucemia is event when typical symptoms of hypoglycemia are accompanied by blood glucose of < 70 mg/dL
Asymptomatic hypoglycemia is ____
Asymptomatic hypoglycemia is event not accompanied by typical symptoms of hypoglycemia but with a blood glucose of < 70 mg/dL
Probable symptomatic hypoglycemia is ____
Probable symptomatic hypoglycemia is symptoms of hypoglycemia without a blood glucose but presumably caused by a blood glucose < 70 mg/dL
Pseudo-hypoglycemia is ____
Pseudo-hypoglycemia is reporting typical symptoms of hypoglycemia with measured blood glucose > 70 mg/dL but approaching that level (trend of hypoglycemia)
Whipple’s triad is ____, ____, and ____
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
First line of defense is when blood glucose is ____ and involves ____
First line of defense is when blood glucose is 80-85 mg/dL and involves decreased insulin
Second line of defense is when blood glucose is ____ and involves ____
Second line of defense is when blood glucose is 65-70 mg/dL and involves increased glucagon
Third line of defense is when blood glucose is ____ and involves ____
Third line of defense is when blood glucose is 65-70 mg/dL and involves increased epinephrine
Describe systemic glucose balance and glucose counter-regulation
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
During fasting state, normal blood glucose is ____ with transient higher excursions after a meal
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
Between meals and during fasting, plasma glucose levels are maintained by ____, ____, and ____
Between meals and during fasting, plasma glucose levels are maintained by endogenous glucose production, hepatic glycogenolysis, and hepatic and renal gluconeogenesis
Describe clinical manifestations of hypoglycemia
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
General causes of hypoglycemia in ill-appearing individuals are ____, ____, ____, and ____
General causes of hypoglycemia in ill-appearing individuals are drugs, critical illness, hormone deficiences, and non-Islet tumors
General causes of hypoglycemia in healthy-appearing individuals are ____ and ____
General causes of hypoglycemia in healthy-appearing individuals are endogenous hyperinsulinism and insulin autoimmune hypoglycemia
____ is the limiting factor in management of diabetes
Hypoglycemia is the limiting factor in management of diabetes
- Causes recurrent morbidity in T12DM and T2DM
___ is a risk factor for hypoglycemia in diabetes
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
Hypoglycemia associated autonomic failure is ____
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
Hypoglycemia begets _____
Hypoglycemia begets hypoglycemia
Describe hypoglycemia-associated autonomic failure
Hypoglycemia-associated autonomic failure
Hypoglycemia is ___ in the absence of diabetes
Hypoglycemia is rare in the absence of diabetes
- Hypoglycemic disorder present only when Whipple’s triad can be demonstrated
_____, _____, _____, and _____ can cause hypoglycemia without diabetes
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
Ethanol blocks ____ but not ____
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
Non-beta cell tumors cause ___
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
People with large mesenchymal or epithelial tumors such as ____, ____, or ____ may have fasting hypoglycemia
People with large mesenchymal or epithelial tumors such as hepatomas, adrencortical carcinomas, and carcinoids may have fasting hypoglycemia
(non-beta cell tumors)
Non-beta cell tumors cause hypoglycemia due to ____
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
Describe diagnosis of non-beta cell tumors
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
Describe causes of endogenous hyperinsulinism
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)
____ is a treatable cause of potentially fatal hypoglycemia and can be sporadic or genetically inherited (MEN 1)
Insulinoma is a treatable cause of potentially fatal hypoglycemia and can be sporadic or genetically inherited (MEN 1)
Insulinoma pathophysiology involves ____
Insulinoma pathophysiology involves failure of insulin secetion to fall to very low levels during hypoglycemia (tumoral production)
- Almost all in pancreas
Insulinoma diagnosis involves measuring hormones during ___
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
These are ____
These are insulinomas
(surgical resection generally curative)
Describe post-gastric bypass hypoglycemia
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
Describe accidental, surreptitious, or malicious hypoglycemia
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
Describe diagnosis of accidental, surreptitious, or malicious hypoglycemia
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)
Hypoglycemia from inaccurate glucose measurements is ___
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)
