Endometriosis was associated with a 46% increased risk of developing type 2 diabetes (T2D), with the magnitude of the association varying by disease subtype and metabolic characteristics.
The investigators conducted the retrospective Advancing Research on Cardiovascular Health and Endometriosis Study using the Utah Population Database. The analysis included nearly 2.94 million patients assigned female at birth who were followed from 1996 to 2021; 99,978 received an endometriosis diagnosis during follow-up. Endometriosis was treated as a time-varying exposure, and incident T2D was identified using diagnostic codes. Researchers also examined associations according to endometriosis subtype, menopausal status, body mass index (BMI), and history of gestational diabetes mellitus (GDM).
Following adjustment for birth state, birth year, race and ethnicity, age, and BMI at cohort entry, patients with endometriosis had a 46% higher risk of developing T2D compared with those without endometriosis. The association remained elevated across multiple sensitivity analyses, although estimates were attenuated under some alternative approaches.
The magnitude of the association differed by endometriosis subtype. The strongest association was observed among patients with anatomically specified “other site” endometriosis, who had approximately 2.7 times the risk of T2D compared with patients without endometriosis. Unspecified “other site” endometriosis was associated with approximately 2.5 times the risk. Elevated risks were also observed with superficial peritoneal, ovarian, and deep infiltrating endometriosis.
The authors cautioned that the subtype estimates should not be directly compared. Each subtype was assessed in a separate model that excluded patients with other endometriosis subtypes from the reference group.
Metabolic characteristics also appeared to modify the association. Among patients with a BMI below 30 kg/m², endometriosis was associated with more than twice the risk of T2D. The association remained elevated but was smaller among patients with a BMI of 30 kg/m² or greater.
Differences were also observed by age-based menopausal status. Among patients younger than 50 years, endometriosis was associated with a 55% higher risk of T2D. The researchers used age younger than 50 years as a proxy for premenopausal status because clinical menopause was not reliably captured in the database.
Among parous patients with available birth records, endometriosis was associated with elevated T2D risk regardless of GDM history. The researchers suggested that this finding indicated pregnancy-related dysglycemia did not fully explain the observed relationship between endometriosis and subsequent T2D.
Several sensitivity analyses supported the overall direction of the findings. Results remained similar when researchers accounted for potential delays in endometriosis diagnosis and additionally adjusted for parity and infertility. Analyses incorporating updated measures of education, smoking, and geographic residence also produced similar findings. However, when the exposed group was restricted to patients with endometriosis and a recorded laparoscopy, the association was attenuated to a 31% increased risk of T2D.
Most endometriosis diagnoses were identified using administrative codes, creating the potential for misclassification, particularly by subtype. The “other site” category associated with the greatest T2D risk was especially heterogeneous and may have reflected both complex disease and nonspecific coding.
Surveillance bias was also possible because patients with endometriosis may have more frequent interactions with the health care system, increasing opportunities to detect otherwise asymptomatic T2D. The attenuation observed in the laparoscopy-restricted analysis may have reflected improved exposure ascertainment and differences in health care use, although that surgically evaluated population was also highly selected. Residual confounding from unmeasured factors, including diet, physical activity, and hormonal treatments, could not be excluded.
Because the study was observational, the findings do not establish that endometriosis causes T2D. Instead, they suggest that endometriosis may be associated with increased long-term metabolic risk and that the strength of the association may differ across disease subtypes and metabolic profiles.
“These findings may have implications for future research on metabolic risk assessment among individuals with endometriosis,” wrote Maggie Fuzak Nunziato, of the College of Public Health at George Mason University, and colleagues.
Disclosures: The authors reported no relevant conflicts of interest.
Source: Diabetologia
