MON-599 - MODY-9 Unmasked in A Patient Initially Diagnosed with Autoimmune Diabetes (Type 1.5/LADA): Dramatic Glycemic Improvement with Sulfonylurea and Reduced Insulin Requirement

Background:
Maturity-onset diabetes of the young (MODY) is the most common form of monogenic diabetes, accounting for approximately 2–5% of all diabetes cases (1). MODY results from a single-gene mutation leading to impaired down-regulated glucose-stimulated beta-cell insulin secretion (2). MODY is linked to mutations in at least 14 different genes, and many variants have been identified. MODY-9 is a rare monogenic diabetes caused by heterozygous PAX4 mutations (3). MODY classically presents before age 25, is non-ketotic, and usually lacks pancreatic autoantibodies (2). This patient we are presenting was first diagnosed with LADA. Over time, her insulin requirement increased more than expected. Genetic testing was performed and confirmed MODY-9. High GAD antibody positivity is very rare in monogenic diabetes, making this case uncommon

Case Presentation:
A 43-year-old female, from Pakistan and of South Asian ethnicity, was diagnosed with LADA in her 30s. Her blood sugar in Continuous Glucose Monitoring (CGM) remained persistently in the 200–300 mg/dL range despite strict adherence to basal–bolus insulin. C-peptide 1.30 ng/mL was measured at a blood glucose of 212 mg/dL, GAD >250 IU/mL, showing preserved but low beta-cell function. She never developed DKA. Family history was notable for multigenerational diabetes and autoimmune diseases, including celiac disease and lupus. Over the years, her insulin requirement increased disproportionately despite compliance, raising suspicion for an underlying monogenic component. MODY genetic testing was performed and confirmed a heterozygous PAX4 variant (c.223C>G, p.P75A) with an autosomal dominant inheritance pattern, consistent with MODY-9. After initiation of low-dose sulfonylurea therapy, her glucose levels improved dramatically, and her insulin requirement reduced significantly. Her CGM readings stabilized around the low 100s, and A1c reached the target goal.

Conclusion:
MODY is often misclassified as either Type 1 or Type 2 diabetes (1). MODY-9 should be suspected in antibody-positive adults when insulin requirement rises unexpectedly without ketosis. Early genetic diagnosis enables targeted sulfonylurea therapy reduces insulin burden, improves glycemia and may help prevent long-term complications.

References:
1. McDonald TJ, Colclough K, Brown R, et al. Diabet Med. 2011;28(9):1028–1033. doi:10.1111/j.1464-5491.2011.03287.x
2. Hoffman LS, Fox TJ, Anastasopoulou C, et al. StatPearls Publishing. Updated 2023 Aug 14.
3. Tao J, Wang H, et al. Identification and Characterization of Novel PAX4 Variants in Patients with Suspected MODY9. BMJ Open Diabetes Research & Care. 2025;13:e005375.

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