Endocrine Abstracts

JOINT3683

Gestational Diabetes Mellitus (GDM) is a common pregnancy-related condition, affecting 14. 2% of women worldwide and 12. 2% in Europe. It increases the risk of long-term complications for both mother and child, including cardiovascular disease, obesity, and type 2 diabetes (T2D). Early diagnosis and appropriate management are crucial in minimizing these risks. Although the exact causes of GDM remain unclear, it is linked to insufficient insulin production and an inability to counteract pregnancy-induced insulin resistance. Genetic factors are increasingly recognized as contributors to GDM development. Variants in SLC30A8 (rs13266634, rs11558471) and CDKAL1 (rs10946398) have been associated with alterations in insulin secretion, beta-cell function, and glucose regulation. Additionally, SNPs near genes responsible for pancreatic development, such as rs1111875, rs5015480, and rs7923837 in HHEX, have been linked to an increased risk of GDM in several studies. This study investigates the association between the SNPs mentioned above and the risk of GDM in the Polish population and evaluates their impact on phenotypic traits using mathematical indices of insulin resistance (HOMA-IR), insulin sensitivity (Matsuda index), and beta-cell function (IGI, DI30, DI120, and AUC-based indices), calculated from a four-point glucose tolerance test. A total of 104 women diagnosed with GDM and 372 normoglycemic controls (NGT) were included in the study. Women with GDM exhibited higher glucose levels, greater insulin resistance (HOMA-IR), and reduced indices of beta-cell function (P < 0. 0001). GDM was significantly associated with SLC30A8 polymorphisms in both the dominant model (rs13266634: OR 1. 63 [1. 04-2. 53], rs11558471: OR 2. 02 [1. 28-3. 16]) and the allelic model (OR 1. 47 [1. 03-2. 09] and OR 1. 68 [1. 17-2. 41]). Additionally, rs10946398 in CDKAL1 showed an association with GDM in both the genotypic (OR 1. 77 [1. 1-2. 83]) and allelic models (OR 1. 4 [1. 02-1. 91]) (P < 0. 05). Carriers of the risk genotypes exhibited higher glucose levels and impaired insulin secretion in response to glucose, as reflected by the disposition index (DI), ΔAUCins/glc, and reduced beta-cell function (IGI index) across the study population (P < 0. 05). This study confirms the association between SLC30A8 and CDKAL1 polymorphisms and an increased risk of GDM. Carriers of risk genotypes exhibited higher glucose levels and impaired beta-cell function, indicating a genetic influence on glucose metabolism during pregnancy. Identifying these SNPs could aid in early detection of GDM, enabling personalized management strategies to improve maternal and fetal outcomes and reduce the long-term risk of type 2 diabetes. These findings support the potential clinical use of genetic testing to identify high-risk individuals and implement targeted interventions.