CDE Pathophysiology 3 — Questions and Answers
Question 1: Which of the following best describes the pathophysiology of hyperosmolar hyperglycemic state (HHS)?
- Complete insulin deficiency with unrestricted ketogenesis
- Relative insulin deficiency sufficient to prevent ketosis but insufficient to control glucose (Correct answer)
- Normal insulin levels overwhelmed by counterregulatory hormones
- Glucagon deficiency allowing unrestricted hepatic glucose output
Correct answer: Relative insulin deficiency sufficient to prevent ketosis but insufficient to control glucose
In HHS, residual insulin secretion is enough to suppress hepatic ketogenesis but insufficient to prevent extreme hyperglycemia, resulting in severe hyperosmolality without significant ketoacidosis.
Question 2: The Somogyi effect refers to morning hyperglycemia caused by:
- Growth hormone surge during early morning hours
- Rebound hyperglycemia following nocturnal hypoglycemia (Correct answer)
- Insufficient basal insulin coverage overnight
- Dawn phenomenon with cortisol-mediated glucose release
Correct answer: Rebound hyperglycemia following nocturnal hypoglycemia
The Somogyi effect describes rebound hyperglycemia occurring after nocturnal hypoglycemia triggers counterregulatory hormone release (glucagon, epinephrine, cortisol) that overshoots glucose correction.
Question 3: Peripheral insulin resistance in skeletal muscle primarily involves impairment of:
- GLUT-1 transporter expression on cell membranes
- Insulin receptor tyrosine kinase activity and IRS-1 phosphorylation (Correct answer)
- Glycolytic enzyme production in the cytoplasm
- Mitochondrial ATP synthesis needed for glucose oxidation
Correct answer: Insulin receptor tyrosine kinase activity and IRS-1 phosphorylation
Skeletal muscle insulin resistance centers on defective insulin receptor tyrosine kinase activation and downstream IRS-1 phosphorylation, impairing PI3K/Akt signaling and GLUT-4 translocation.
Question 4: In type 2 diabetes pathogenesis, the role of adipose tissue dysfunction includes:
- Decreased lipolysis causing low free fatty acid levels
- Increased secretion of adiponectin improving insulin sensitivity
- Ectopic fat deposition and pro-inflammatory adipokine release (Correct answer)
- Adipose tissue becoming the primary site of insulin clearance
Correct answer: Ectopic fat deposition and pro-inflammatory adipokine release
Dysfunctional adipose tissue in type 2 diabetes releases excess free fatty acids, pro-inflammatory cytokines (TNF-α, IL-6), and reduced adiponectin, contributing to systemic insulin resistance and inflammation.
Question 5: Counterregulatory hormone deficiency in long-standing type 1 diabetes most commonly manifests as:
- Impaired glucagon response to hypoglycemia (Correct answer)
- Loss of cortisol secretion during stress
- Absence of growth hormone nocturnal surges
- Reduced ACTH secretion from the pituitary
Correct answer: Impaired glucagon response to hypoglycemia
After several years of type 1 diabetes, the glucagon counterregulatory response to hypoglycemia becomes severely blunted, contributing to hypoglycemia unawareness and increased severe hypoglycemia risk.
Question 6: Neonatal diabetes mellitus differs from type 1 diabetes primarily in that it:
- Is always transient and resolves by 3 months of age
- Results from monogenic mutations affecting beta-cell function rather than autoimmunity (Correct answer)
- Requires higher insulin doses per kilogram than adult type 1
- Is caused by maternal gestational diabetes transferring antibodies
Correct answer: Results from monogenic mutations affecting beta-cell function rather than autoimmunity
Neonatal diabetes is a monogenic disorder caused by mutations in genes such as KCNJ11 or ABCC8 that impair beta-cell ATP-sensitive potassium channels, and is not autoimmune in origin.
Question 7: The mechanism by which obesity promotes type 2 diabetes risk involves which adipose-related pathway?
- Increased adiponectin from enlarged adipocytes improving glucose uptake
- Macrophage infiltration into adipose tissue generating chronic low-grade inflammation (Correct answer)
- Leptin deficiency preventing satiety and causing overeating only
- Brown adipose tissue expansion increasing thermogenesis and insulin demand
Correct answer: Macrophage infiltration into adipose tissue generating chronic low-grade inflammation
Enlarged adipocytes recruit macrophages that release TNF-α and IL-6, creating chronic low-grade inflammation that impairs insulin signaling in muscle and liver, linking obesity to insulin resistance.
CDE Pathophysiology 3
Which of the following best describes the pathophysiology of hyperosmolar hyperglycemic state (HHS)?