The MODY Masquerade

Abstract

Introduction: Maturity Onset Diabetes of the Young (MODY) is a relatively uncommon, but increasingly recognized cause of diabetes. Many MODY patients are misdiagnosed as type 1 or type 2 diabetes mellitus (DM) and may be treated suboptimally for many years before they are recognized. We present one such patient who went 49 years before accurate diagnosis. Case: A 59 year-old female with a history of type 2 DM presented with complaints of difficulty controlling her blood sugar. She was being treated with metformin, and had been recently started on low dose glimepiride due to persistently elevated hemoglobin A1c (HbA1c). She was diagnosed as type 2 DM at 10 years of age. Her weight was normal at the time of diagnosis, and she did not require insulin. Family history included many family members diagnosed as type 2 DM, including her maternal grandmother, mother, brother, sister, son, and two nieces. All were diagnosed in their teens, and only her son currently requires insulin. On exam, she was not obese (BMI 26 kg/m2) with no signs of insulin resistance. Antibodies to glutamic acid decarboxylase (GAD Ab) were undetectable, and C-peptide was elevated to 4.04 ng/mL in response to mild hyperglycemia. Genetic testing revealed a defect in the Hepatocyte Nuclear Factor 4 Alpha (HNF4A) gene, consistent with MODY subtype 1. The dose of glimepiride was increased, and her HbA1c improved from 8.1% to 6.1% after two months. Discussion: MODY is a form of diabetes caused by single gene mutations related to beta cell development, regulation, and function. These defects lead to impaired glucose sensing and insulin release. MODY should be suspected in patients with a strong family history of diabetes, lack of signs of insulin resistance, onset at young age, and absence of features of type 1 DM (i.e., negative GAD Ab and detectable C-peptide). MODY subtype 1 patients are typically sensitive to sulfonylurea therapy, and this is considered first-line treatment. However, some patients may develop progressive beta cell dysfunction as they age and will ultimately require insulin therapy. Disclosure D. Englert: None. J. Dendy: None.