MON-555 PPARγ Genetic Variant c 1169del. A Not So Common Case of Induced Insulin Resistance

Abstract Disclosure: A. Contreras-Arce: None. A. Pechir-Cerrillo: None. V. De la Pena Gil: None. C. Castillo-Castro: None. P. Portillo-Sanchez: None. Introduction: Insulin resistance is a complex disorder associated with the development of metabolic abnormalities. It is considered to be a pivotal cause of an increased group of comorbidities and overall mortality. Its pathophysiology involves genetic and environmental factors. However, the identification of genetic variants associated with multiple metabolic pathways is not so commonly performed. There is significant role on glucose metabolism of Peroxisome Proliferator-Activated Receptor Gamma (PPARy). Clinical presentation: A 48-year-old female was evaluated in the Endocrinology clinic for Insulin Resistance. Family history of a sister with Metabolic Syndrome. Patient had no comorbidities. Denied any symptoms or significant weight changes. On physical exam, vital signs and BMI within normal range, there was presence of acanthosis nigricans and soft fibromas at the level of the neck, no other remarkable findings were observed. Patient had a normal BMI. Laboratories showed glucose 77 mg/dL, Insulin 12 uUI/mL, HbA1c 4.9 %, Total Cholesterol 272 mg/dL, HDL 40 mg/dL, LDL 173 mg/dL, Triglycerides 239 mg/dL. A 75-gram Oral Glucose Tolerance Test showed basal glucose 91 mg/dL and 150 mg/dL after 120 min, basal insulin levels 30 uU/mL and 780 uU/mL after 120 min. Negative anti insulin antibodies, C-Peptide 3.35 ng/mL. CT Abdomen reported Cholecystolithiasis and no abnormal findings at the level of the pancreas. Genetics was consulted to rule out a metabolic disorder. A genetic variant of gene PPARy c 1169del p(Asp390Alas*11). Laboratories and acanthosis improved with treatment. Discussion: The pathophysiology of insulin resistance involves both genetic and environmental factors. PPARy is a protein that functions as a crucial factor in the regulation of insulin sensitivity primarily influencing adipocyte differentiation, lipid metabolism and interactions with other metabolic pathways to maintain homeostasis. The variant identified on this patient was PPARy gene c.1169del p.(Asp390Alafs*11), which results in a frameshift starting at codon 390 and leads to a stop codon 10 positions ahead. This genetic variant has been linked to further development of insulin resistance and familial partial lipodystrophy. Conclusion: Insulin resistance encompasses a wide variety of metabolic conditions. Therefore, it is important to highlight the need to explore new methods for early detection using diagnostic tools that incorporate genetic testing. Generating awareness in healthcare providers for a prompt and more targeted treatment in order to adequately prevent its complications and mortality. Presentation: Monday, July 14, 2025