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

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.

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).

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).

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.