Abstract
Disclosure: B. Celik: None. L. De Mattei: None. J. Meireles: None. M.R. Brennan: ; Dr. Brennan is a paid consultant for Novo Nordisk, Boehringer Ingelheim, and Bayer.. IntroductionMultiple endocrine neoplasia type 1 (MEN1) is a syndrome characterized by a predisposition to tumors of the parathyroid, pituitary, and enteropancreatic cells. It is known that patients with MEN1 have a reduced life expectancy, and the incidence of cardiovascular diseases is increased in this patient group. Multiple studies have reported an increased risk of impaired glucose metabolism in patients with MEN1. In this study, we aimed to evaluate the association between MEN1 syndrome and insulin resistance. MethodsA systematic search was conducted across PubMed, EMBASE, Scopus, Cochrane Library, and Web of Science from inception to February 6, 2025, following PRISMA 2020 guidelines. Studies involving at least five patients with MEN1 and reporting on insulin resistance were included. Two independent reviewers performed study selection, data extraction, and quality assessment. Independent t-tests were used for continuous variables and chi-square tests for binary variables. Statistical significance was set at p < 0.05.ResultsOut of 1453 studies, 5 met the inclusion criteria, involving 606 patients with MEN1 and 4431 controls. The mean age was comparable between MEN1 and control groups (43.28 ± 13.64 vs 43.00 ± 13.38 years, respectively; p = 0.687), as was the proportion of male participants (37% vs 36%; p = 0.604). Similarly, mean BMI values did not differ significantly between groups (26.32 ± 5.53 kg/m² vs 26.64 ± 6.44 kg/m²; p = 0.728). The prevalence of insulin resistance was significantly higher in patients with MEN1 compared to controls (25% vs 5%, OR 6.46, 95% CI 5.15-8.1, p < 0.0001). Additionally, MEN1 patients exhibited significantly elevated HOMA-IR values compared to controls (3.37 ± 2.21 vs 2.13 ± 0.79, 95% CI 0.99-1.55, p < 0.0001).DiscussionTo our best knowledge, this represents the first systematic review on MEN1 and insulin resistance. We have identified a higher prevalence of insulin resistance among individuals with MEN1 compared to controls, independent of age, sex, or BMI. Primary hyperparathyroidism is the most common endocrinopathy associated with MEN1, exhibiting a penetrance of over 90%. Hypercalcemia is known to affect glucose metabolism and likely plays a significant role in the development of insulin resistance among patients with MEN. The MEN1 gene encodes menin, a tumor suppressor protein that also plays a crucial role in hepatic glucose uptake. Multiple animal studies have demonstrated that decreased expression of menin is associated with insulin resistance. The genetic loss of menin in patients with MEN1 may provide a plausible explanation for the observed increase in insulin resistance, as indicated by our study. Given these findings, we recommend that patients with MEN1 should be screened early in the disease course for impaired glucose tolerance, as this may help prevent future cardiovascular events and enhance life expectancy. Presentation: Sunday, July 13, 2025