Trace elements and risk of diabetes-related vascular complications: results from the EPIC-Potsdam cohort study.

Background: The trace elements selenium, zinc, copper, manganese, iodine, and iron are crucial for various physiological processes, including enzymatic reactions and immune responses. Dyshomeostasis of trace elements is associated with a variety of diseases including diabetes and cardiovascular diseases. It has not been clarified whether blood trace elements associate with the risk of diabetes-related vascular complications. We aimed to investigate the prospective associations between pre-diagnosis serum levels of trace elements with vascular complications in diabetes.

Methods: Participants with incident diabetes and free of micro- and macrovascular disease and with pre-diagnostic serum trace element measurements from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 627) were followed for microvascular and macrovascular complications (n = 212 and n = 69, respectively, median follow-up: 12.8 years). We used Cox Proportional Hazard models to investigate the associations between baseline trace element levels (per SD difference) and the risk of developing diabetes-related vascular complications. To investigate the interactions and nonlinear associations between TEs and risk of diabetes-related complications, we applied Bayesian kernel machine regression (BKMR).

Results: In multivariable models, higher iodine levels were associated with higher risk of developing total vascular complications (HR per SD, 95% CI: 1.16, 1.02-1.31) and microvascular complications (1.18, 1.03-1.35). In sex-stratified analyses we observed significant positive associations between zinc and total vascular complications (1.35, 1.06-1.73) and microvascular complications (1.52, 1.15-2.02) in women, while higher zinc was associated with increased risk of macrovascular complications in men (1.33, 1.00-1.77). Copper-to-Zinc ratio was inversely associated with the risk of microvascular complications in women (0.69, 0.54-0.88), but with an increased risk in men (1.54, 1.17-2.02).

Conclusions: Our findings indicate that higher serum levels of iodine measured prior to the diagnosis of diabetes are associated with higher risk of subsequent microvascular complications in diabetes, while copper-to-zinc ratio is associated with microvascular complications in a sex-specific manner.