SAT092 A Case Of Mature Onset Diabetes Of The Young

Abstract

Abstract Disclosure: L. Beshay: None. A. Thakkar: None. Background: Maturity onset diabetes of the young (MODY) is a disorder characterized by noninsulin-dependent diabetes diagnosed at a young age (<25 years) with autosomal dominant inheritance and lack of autoantibodies. It accounts for 2 to 5 percent of diabetes cases. Several different genetic abnormalities have been identified causing disruption in pancreatic beta cells development and function leading to impaired insulin secretion. Mutations in hepatocyte nuclear factor-1-alpha (HNF1A) is the most commonly identified mutation occurring in 52 to 65 of MODY cases. Case Description: A 21 year old female with a history of diabetes and recurrent skin abscesses presented to the emergency room with right lower quadrant epidermal abscess. Endocrinology was consulted for evaluation of her diabetes. She was diagnosed at age 14 when she presented with weight loss, polyuria, polydipsia, BG 406 without diabetic ketoacidosis. She reported a history of type 2 diabetes in mother. Her medications included metformin, lantus and humalog. It was noted that her diabetes was never controlled with an A1c persistently >10%. Patient reported skin swelling with insulin injections and working two jobs which limited her ability to take more than one injection per day. Her BMI is 23 kg/m2. Labs this admission showed HbA1c 13.7%, GAD 65 Ab and IA-2 Ab negative, c-peptide 1.1 ng/ml, with a glucose of 209 mg/dl. MODY was suspected due to her age, intact c-peptide, and lack of DM1 antibodies. The patient was discharged on Trulicity 0.75 mg weekly, Lantus 12U nightly, Glipizide 2.5mg daily. On follow up, a MODY genetic panel confirmed a HNF1A missense variant with AD inheritance. Since initiation of sulfonylurea, she has had improved control of diabetes. Glipizide dose is being titrated up with concomitant decrease in insulin dose with plan to discontinue basal insulin once her blood sugars are at goal. Conclusion: The HNF1A gene on chromosome 12 is a weak transactivator of the insulin gene in beta cells. Mutations of HNF1A can lead to abnormal insulin secretion and a low renal threshold for glucose. These patients are at risk for micro- and macrovascular complications of diabetes. In terms of treatment, they exhibit increased insulin sensitivity and marked sensitivity to the hypoglycemic effects of sulfonylureas compared with patients with type 2 diabetes. Thus, patients can be successfully treated with sulfonylurea monotherapy, and in one clinical study, approximately 70 percent of patients previously treated with insulin successfully switched to sulfonylureas. Thus, it is important to evaluate etiology of diabetes, as detection of MODY variants in which sulfonylureas are used for treatment simplifies management and improves outcomes as demonstrated in this case. Presentation: Saturday, June 17, 2023