Diabetes Pathophysiology Flashcards

Which concept describes the persistent increased risk of diabetic complications even after achieving good glycemic control, due to epigenetic changes from prior hyperglycemia?

Answer: Metabolic memory (hyperglycemic memory)

Metabolic memory refers to epigenetic modifications — including histone methylation and DNA methylation changes — imprinted during periods of hyperglycemia that sustain vascular damage even after normoglycemia is restored.

In the context of diabetic neuropathy, which mechanism specifically drives the pain and allodynia characteristic of small-fiber neuropathy?

Answer: Sensitization and ectopic discharge of damaged C-fibers and A-delta nociceptors due to oxidative stress and AGE accumulation

Small unmyelinated C-fibers and thinly myelinated A-delta nociceptors become hyperexcitable and fire ectopically when damaged by oxidative stress and AGE-mediated pathways in diabetic neuropathy.

Which hormonal change during puberty most significantly worsens insulin resistance and increases insulin requirements in adolescents with type 1 diabetes?

Answer: Pubertal rise in growth hormone reducing peripheral insulin sensitivity

The pubertal rise in growth hormone, which peaks nocturnally, substantially reduces insulin sensitivity in peripheral tissues and requires up to 50% more insulin to maintain glycemic targets.

What is the pathophysiological basis for the hyperchloremic non-anion gap metabolic acidosis that can occur after treatment of diabetic ketoacidosis?

Answer: Saline infusion provides a chloride load while ketones are excreted as sodium salts, depleting bicarbonate regeneration capacity

During DKA treatment, large-volume normal saline delivers excess chloride, and urinary loss of sodium ketonate salts removes potential bicarbonate; together these produce a dilutional hyperchloremic acidosis.

Which pathophysiological mechanism links obesity-induced chronic low-grade inflammation to skeletal muscle insulin resistance?

Answer: Excess free fatty acids and inflammatory cytokines (TNF-α, IL-1β) activate IKK-β and JNK, which serine-phosphorylate and inhibit IRS-1

FFA and pro-inflammatory cytokines from hypertrophied adipocytes activate IKK-β and JNK serine kinases that phosphorylate IRS-1 at inhibitory serine residues, blocking the insulin signaling cascade.

In type 2 diabetes, what explains the paradoxical finding of elevated circulating insulin alongside hyperglycemia in early disease?

Answer: Peripheral insulin resistance requires compensatory beta-cell hypersecretion, but glucose cannot be effectively utilized

Early T2D is characterized by compensatory hyperinsulinemia as beta cells attempt to overcome peripheral insulin resistance; the hyperglycemia reflects ineffective insulin action rather than absolute deficiency.

Which form of monogenic diabetes is caused by heterozygous loss-of-function mutations in HNF-1α and is particularly sensitive to sulfonylurea therapy?

Answer: MODY3 (HNF-1α mutation)

MODY3, caused by HNF-1α mutations, impairs transcriptional regulation of the SUR1 sulfonylurea receptor pathway and paradoxically responds dramatically to low-dose sulfonylureas, often replacing insulin therapy.