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Teachable Moment
September 16, 2024

Diagnostic Inertia in Identifying Maturity-Onset Diabetes of the Young

Author Affiliations
  • 1Amedes Endokrinologikum Ulm, Ulm, Germany
JAMA Intern Med. 2024;184(11):1384-1385. doi:10.1001/jamainternmed.2024.2931

A 34-year-old woman, who had received a diagnosis of type 1 diabetes 19 years ago and had been treated with insulin therapy, presented to our outpatient endocrinology department for the first time for follow-up. She had no family history of diabetes, but her son was diagnosed with type 1 diabetes at age 12 years. She had no history of diabetic ketoacidosis. Initial laboratory tests revealed normal levels of C-peptide, indicating sufficient endocrine pancreatic function. Given this unusual finding and considering the duration of the disease, we conducted tests for diabetic-specific autoantibodies (islet cell antibodies, antibodies to glutamic acid decarboxylase 65, insulin autoantibodies, insulinoma associated-2 autoantibodies to protein tyrosine phosphatase, and anti-zinc transporter 8 antibodies), which returned negative results. Considering her young age, normal body mass index, and normal C-peptide levels, we began to consider the differential diagnosis of maturity-onset diabetes of the young (MODY). Subsequent genetic testing revealed a heterozygous c.1340C>T; p.(Pro447Leu) variant in the HNF1A gene, confirming the presence of MODY (formerly MODY 3).1 This diagnosis led us to stop her insulin and initiate sulfonylurea. Discontinuing insulin therapy led to a substantial improvement in the patient’s quality of life. The patient’s MODY diagnosis additionally prompted the screening of her affected son, which revealed the presence of the same gene variant and also led to a revision of the diagnosis.

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