A type 1 diabetic on intensive insulin therapy notices that after several years of tight control, his hypoglycaemia warning symptoms have diminished. This syndrome of hypoglycaemia unawareness is related to failure of which counterregulatory response?

• A Failure of cortisol secretion from the adrenal cortex as the primary counterregulatory hormone
• B Failure of growth hormone secretion from the anterior pituitary gland
• C Downregulation of cerebral glucose transporters causing delayed neuroglycopenia
• D Failure of glucagon secretion from pancreatic alpha cells combined with impaired epinephrine release from the adrenal medulla ✓

Explanation

In long-standing type 1 diabetes, pancreatic alpha cells lose their ability to secrete glucagon in response to hypoglycaemia (a defect occurring early in disease). With repeated hypoglycaemia, the adrenal medullary epinephrine response also becomes blunted (hypoglycaemia-associated autonomic failure). Together, these deficiencies produce hypoglycaemia unawareness — the patient loses both symptom generation (adrenergic) and the counterregulatory response. Cortisol and growth hormone are slower-acting counterregulatory hormones and are not primarily responsible for unawareness.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.