Long-term adverse multi-system health outcomes of gestational diabetes mellitus: an analysis of real-world cohort data

BACKGROUND: There is emerging evidence that gestational diabetes mellitus (GDM) increases the risk of multi-system long-term complications such as cancer and autoimmune disease, however this evidence is scarce and conflicting. Therefore, we aim to explore the long-term health implications of GDM. METHODS: We performed analyses using TriNetX in women ≥ 18 years who had a birth. Four cohorts were generated with a reference and GDM arm, and PSM 1:1 for factors including age, BMI, and cohort-specific risk factors. The cohort sizes were metabolic n = 72,014, cancer n = 88,131, autoimmune n = 96,110, and gynaecological n = 94,945. RESULTS: GDM increased the risk of 5-year incident clinical outcomes: metabolic: T2D (HR 18.42, p < 0.0001), hypertriglyceridemia (HR 2.47, p < 0.0001), obesity (HR 1.89, p < 0.0001), and sleep apnoea (HR 1.83, p < 0.0001); cancer: thyroid cancer (HR 1.34, p = 0.036); autoimmune: type 1 diabetes (HR 12.32, p < 0.001), Grave's disease (HR 1.57, p=<0.0001), and psoriasis (HR 1.25, p = 0.007); and gynaecological PCOS (HR 1.97, p < 0.0001), uterine fibroids (HR 1.29, p < 0.0001), and endometriosis (HR 1.16, p = 0.018). At 10 years, there was a significantly increased risk of the composite 13 adiposity-related cancers (HR 1.18, p = 0.008). CONCLUSION: Women with GDM are at risk of a myriad of long-term adverse health outcomes meriting targeted early intervention and long-term post-partum monitoring.