Glucose metabolism disorders Flashcards
Whipples triad
- Symptoms consistent with hypoglycemia
- Low plasma glucose concentration
- Relief of symptoms after plasma glucose is raised
Blood Glucose ≤ 60 mg/dL
Symptoms of hypoglycemia begin (usually
neurogenic autonomic)
Blood Glucose ≤ 50 mg/dL
Neuroglycopenia (impaired brain function) manifests
Cause of hypoglycemia: Insulinoma
Pancreatic B cell tumor
Pancreatic B cell tumor
Insulinoma: Patient experiences neuroglycopenic symptoms of hypoglycemia
* Confusion, blurred vision, diplopia, anxiety, convulsions
* Immediate recovery upon administration of glucose
* Blood glucose < 45 mg/dL
* Serum Insulin ≥ 6 microunit/mL
Where are Pancreatic B cell tumors found?
99% found in the pancreas, 1% in ectopic pancreatic tissue
Cause of hypoglycemia: Surreptitious administration of insulin or sulfonylureas
Commonly healthcare workers or those with access to a family member’s diabetic medications
Why might Surreptitious administration of insulin or sulfonylureas occur?
Factitious disorder (Munchausen’s syndrome ):
Psychiatric disorder characterized by consciously simulated physical or psychological illness & need to assume a sick role for medical attention & emotional support without external incentive or reward
Cause of hypoglycemia: Extrapancreatic tumors (rare)
retroperitoneal sarcomas, hepatocellular carcinomas, adrenocortical carcinomas, & miscellaneous epithelial-type tumors
Tumors are frequently large & readily palpated or visualized on CT scans or MRI
Cause of hypoglycemia: Functional alimentary hypoglycemia
patient’s symptoms suggest ↑ sympathetic
activity
* Anxiety, weakness, tremor, sweating, or palpitations after meals
* Physical exam & labs are normal*
* *10% of normal patients have glucose levels < 50 mg/dL in a 4-6
hr oral glucose tolerance test
Cause of hypoglycemia: Noninsulinoma pancreatogenous hypoglycemia syndrome
Rarely in patients with organic hyperinsulinism, islet cell hyperplasia is present rather than an adenoma
Patients typically have documented hyperinsulinemic hypoglycemia after meals
but not with fasting up to 72 hours
Cause of hypoglycemia: Occult diabetes mellitus
Characterized by a delay in early insulin release from pancreatic B cells, resulting in initial exaggeration of hyperglycemia during a glucose tolerance test.
* In response to this hyperglycemia, an exaggerated insulin release produces a late hypoglycemia 4–5 hours after ingestion of glucose
Patients are often obese & frequently have a family history of diabetes mellitus
Cause of hypoglycemia: Alcohol-related hypoglycemia
- Hepatic glycogen becomes depleted secondary to malnourishment in alcohol abusers or those unable to ingest food after an acute alcoholic
episode followed by gastritis & vomiting. - Exacerbated when combined with alcohol-mediated inhibition of gluconeogenesis
Cause of hypoglycemia: Immunopathologic hypoglycemia
extremely rare condition in which anti-insulin
antibodies or antibodies to insulin receptors develop spontaneously
Immunopathologic hypoglycemia antibodies
1 Idiopathic anti-insulin antibodies
* mechanism appears to relate to increasing dissociation of insulin from circulating pools of bound insulin, Thus causing hypoglycemia
2 Antibodies to insulin receptors
* most patients do not have hypoglycemia but rather severe insulin-resistant diabetes & acanthosis nigricans.
* However, certain anti-insulin receptor antibodies with agonist activity mimicking insulin action may develop, producing severe hypoglycemia
Hypoglycemia medications
- Fluoroquinolones → especially levofloxacin (Levaquin)-acts on ATP sensitive channels in β cells
- Pentamide → antipneuocystis agent, cytotoxic to β-cells. Causes hyperinsulinemia/hypoglycemia & then insulinopenia/hyperglycemia
- Beta-adrenertic blocking agents → inhibits fatty acids & gluconeogenesis substrate release & ↓ plasma glucagon response
Quinine → Anti-malarial drug - Salicylates → pain reliever found in Aspirin & hundreds of other OTCs
- ACE inhibitors → ↑ sensitivity to circulating insulin by ↑ blood flow to muscle*
Cause of Hypoglycemia: Lactic acidosis
Overproduction (ie tissue hypoxia), Deficient removal (ie liver failure), or both (ie circulatory collapse) causes accumulation. Normally, lactic
acid is converted to glucose in the liver & is returned to muscle cells
Sepsis → severe infection precipitates lactic acidosis → overproduction of
lactic acid
Cause of hypoglycemia: Adrenal Insufficiency
- Clinical syndrome caused by failure of the adrenal cortex to synthesize & secrete adequate amounts of glucocorticoid hormones, & is characterized primarily by cortisol deficiency, with or without aldosterone deficiency.
- Addison disease
- Cortisol production is inadequate to control inflammatory response or to meet
an elevated metabolic demand → hypoglycemia
Neurogenic symptoms of hypoglycemia
- Palpitations
- Tremors
- Arousal/anxiety
- Sweating
- Hunger
- Paresthesias
- Nausea
- feelings of warmth
Neuroglycopenic symptoms of hypoglycemia
- Behavioral changes
- Dizziness
- Fatigue/Drowsiness
- Difficulty speaking
- Headache
- Trouble concentrating/Confusion
- Blurred vision
- Weakness
- Seizures, loss of consciousness
Labs for hypoglycemia
- Glucose
- beta-hydroxybutyrate
- Insulin & Proinsulin
- Circulating oral hypoglycemic agents (sulfonylureas & glinides)
- C-peptide
- Glucose response to glucagon, 1 mg IV
- Insulin antibodies
Insulin antibody positivity indicates ____
autoimmune hypoglycemia
absence of insulin antibody suggests _____
insulinoma, noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS), post-gastric bypass hypoglycemia (PGBH), or circulating oral hypoglycemic agent
insulin < 3 microunits/mL, C-peptide < 0.2 nmol/L (0.6 ng/mL), proinsulin < 5 pmol/L indicates _____
IGF-mediated hypoglycemia (consider nonislet cell tumor, proceed to further dx tests based on suspected tumor type)
