CDE Pathophysiology 2 — Questions and Answers
Question 1: Which mechanism primarily drives beta-cell dysfunction in long-standing type 2 diabetes?
- Autoimmune destruction of beta cells
- Glucotoxicity and lipotoxicity causing oxidative stress (Correct answer)
- Excess glucagon secretion replacing beta cells
- Amyloid deposits blocking insulin secretion entirely
Correct answer: Glucotoxicity and lipotoxicity causing oxidative stress
Chronic hyperglycemia (glucotoxicity) and elevated free fatty acids (lipotoxicity) generate oxidative stress that progressively impairs and destroys beta cells in type 2 diabetes.
Question 2: In type 1 diabetes, the primary immunological mediators of beta-cell destruction are:
- B lymphocytes producing anti-insulin antibodies
- Natural killer cells and complement activation
- Autoreactive CD4+ and CD8+ T lymphocytes (Correct answer)
- Macrophages secreting excess TNF-alpha only
Correct answer: Autoreactive CD4+ and CD8+ T lymphocytes
Autoreactive CD4+ helper and CD8+ cytotoxic T lymphocytes are the principal mediators of beta-cell destruction in type 1 diabetes through a cell-mediated autoimmune process.
Question 3: The incretin effect is significantly reduced in type 2 diabetes primarily because:
- GIP and GLP-1 secretion is completely absent
- Beta-cell responsiveness to GIP is diminished (Correct answer)
- The kidneys rapidly degrade all incretin hormones
- Incretin receptors are blocked by elevated insulin
Correct answer: Beta-cell responsiveness to GIP is diminished
In type 2 diabetes, GLP-1 secretion may be near-normal but beta-cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) is markedly reduced, diminishing the incretin effect.
Question 4: Hepatic insulin resistance in type 2 diabetes primarily leads to:
- Decreased glycogen synthesis and increased gluconeogenesis (Correct answer)
- Increased ketone body production exceeding type 1 levels
- Reduced hepatic glucose uptake only during meals
- Complete suppression of hepatic glucose output at all times
Correct answer: Decreased glycogen synthesis and increased gluconeogenesis
Hepatic insulin resistance impairs insulin's ability to suppress gluconeogenesis and promote glycogen synthesis, resulting in inappropriately elevated fasting hepatic glucose output.
Question 5: Latent autoimmune diabetes in adults (LADA) is best distinguished from type 2 diabetes by:
- Older age at onset and obesity
- Presence of islet autoantibodies such as GAD65 (Correct answer)
- Requirement for insulin within 3 months of diagnosis
- Fasting C-peptide levels above 2 ng/mL
Correct answer: Presence of islet autoantibodies such as GAD65
LADA is characterized by the presence of islet autoantibodies (most commonly anti-GAD65) in adults who initially appear to have type 2 diabetes but have underlying autoimmune beta-cell destruction.
Question 6: During diabetic ketoacidosis, the anion gap increases primarily due to accumulation of:
- Lactic acid from anaerobic metabolism
- Acetoacetate and beta-hydroxybutyrate (Correct answer)
- Elevated chloride from normal saline infusion
- Uric acid from increased purine catabolism
Correct answer: Acetoacetate and beta-hydroxybutyrate
The elevated anion gap in DKA results from accumulation of ketoacid anions—acetoacetate and beta-hydroxybutyrate—produced from accelerated fatty acid oxidation in the absence of insulin.
Question 7: Polydipsia in uncontrolled diabetes mellitus is physiologically triggered by:
- Elevated ADH stimulating thirst centers directly
- Osmotic diuresis causing intravascular volume depletion and hyperosmolality (Correct answer)
- Nausea from ketosis activating thirst reflex
- Kidney failure reducing urine concentration ability
Correct answer: Osmotic diuresis causing intravascular volume depletion and hyperosmolality
Glucosuria exceeds the renal threshold, causing osmotic diuresis with water loss, resulting in hypernatremia and plasma hyperosmolality that stimulates hypothalamic osmoreceptors to trigger thirst.
CDE Pathophysiology 2
Which mechanism primarily drives beta-cell dysfunction in long-standing type 2 diabetes?