A 60-year-old postmenopausal woman with long-standing Type 2 diabetes mellitus presents with postmenopausal bleeding. Transvaginal ultrasound shows endometrial thickness of 9 mm. Endometrial biopsy reveals grade 1 endometrioid adenocarcinoma. She asks why she developed this cancer. Which metabolic mechanism best explains the independent association between diabetes and endometrial carcinoma?
- A Hyperinsulinemia acting via insulin-like growth factor-1 receptors promoting endometrial proliferation ✓
- B Diabetic microvascular disease causing endometrial hypoxia and malignant transformation
- C Ketoacidosis-induced DNA damage in endometrial cells
- D Glycosylation of endometrial progesterone receptors causing functional progesterone resistance
Correct answer: A. Hyperinsulinemia acting via insulin-like growth factor-1 receptors promoting endometrial proliferation
Explanation
Diabetes is an independent risk factor for Type 1 endometrial carcinoma. Hyperinsulinemia in Type 2 diabetes stimulates IGF-1 receptors on endometrial cells, promoting proliferation and inhibiting apoptosis. Obesity and diabetes share insulin resistance as a key pathway. Diabetic microvascular disease is not a recognised carcinogenic mechanism for endometrium. Ketoacidosis is acute and not linked to endometrial carcinogenesis. Progesterone receptor changes occur but are not primarily due to glycosylation.
Reference: Williams Gynecology, 4th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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