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BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome characterized by hyperparathyroidism, pituitary adenomas, and gastro-entero-pancreatic neuroendocrine tumors. Patients with MEN1 mutations have impaired glucose homeostasis, but the role of insulin resistance and beta-cell function is unclear. METHODS: Using a case-control study design, a retrospective analysis of germline mutation-positive MEN 1 patients (n=289) seen at our institution between 1991-2019 was performed. Patients with diabetes and/or insulinoma were excluded. Subjects were age, BMI, sex and race matched 1:1 to unrelated, healthy controls. Fasting glucose, insulin, c-peptide, calcium, PTH, 25-OH vitamin D, cholesterol, LDL, HDL and triglycerides (TG) were compared between two groups. Homeostasis model assessment (HOMA-IR) and HOMA-beta cell function (HOMA-b) were used as surrogate measures of insulin resistance and beta-cell function, respectively. Data is presented as mean ± SD. RESULTS: MEN1 subjects (n=40; age 41±11 years; BMI 29.2±7.2 kg/m2) were matched to healthy controls (age 41±11 years; BMI 29.1±7.5 kg/m2). Only 3 MEN1 patients had no evidence of pancreatic neuroendocrine tumors. Impaired fasting glucose was more prevalent in MEN1 compared with controls (53% vs 10%, p&amp;lt;0.0001). HOMA-IR was positively associated with BMI, but not age, sex, calcium or vitamin D levels in either cohort. HOMA-IR adjusted for age, BMI, and sex was higher in patients with MEN1 compared with controls (4.01 vs. 2.44, adjusted ratio of means 1.54, 95% CI [1.14, 2.07], p=0.005). HOMA-b was not significantly different between the groups (177 vs. 129, adjusted ratio of means 1.17, 95% CI [0.86, 1.58], p=0.23). There were no significant differences in total cholesterol, LDL, HDL, and TG between the groups. CONCLUSION: Lower insulin sensitivity, but not impaired beta cell function may contribute to the higher prevalence of impaired fasting glucose in MEN1 patients compared with controls. Mechanistic studies into the role of menin loss in glucose homeostasis are warranted.

journal of the endocrine society

SUN-128 Impaired Fasting Glucose Is Associated with Insulin Resistance in Patients with Germline Mutations in the Multiple Endocrine Neoplasia Type 1 (MEN1) Gene