Sex-specific association between carbohydrate antigen 19-9 and incident type 2 diabetes

Carbohydrate antigen 19-9 (CA19-9) levels are associated with glycemic control, insulin resistance, and chronic complications in patients with type 2 diabetes (T2D). Women generally show higher CA19-9 levels despite a greater T2D prevalence in men. We evaluated the sex-specific longitudinal associations between CA19-9 levels and T2D incidence. Korean adults (n = 329,380) without previous cancer or T2D were categorized into four groups based on their CA19-9 levels. The study end point was the development of incident T2D during follow-up. Cox proportional hazards models were used to estimate hazard ratios (HR) according to CA19-9 levels. During a median follow-up of 6.1 years (3.3-9.3 years), the incidence rates of T2D were 9.9 per 1,000 person-years in men and 3.6 per 1,000 person-years in women. In the time-dependent analysis, adjusted HRs (95% confidence intervals) for incident T2D comparing CA19-9 levels of 10.0-19.9, 20.0-29.9, and ≥ 30 U/mL to the reference (< 10 U/mL) were 1.08 (1.04-1.13), 1.18 (1.07-1.30), and 1.64 (1.35-1.99), respectively, among men. However, this association was not observed in women. The association between CA19-9 category and incident T2D significantly differed by sex (P_interaction = 0.006). Among young and middle-aged Korean adults, elevated CA19-9 levels were significantly associated with increased risk of type 2 diabetes in men but not in women. Elevated CA19-9 levels in men could be a useful marker for identifying individuals at high risk of developing T2D. Evaluation approaches for individuals with elevated CA19-9 levels should be sex-specific.