Association of Blood Heavy Metals with Diabetic Foot Ulcers in US Adults with Diabetes: Insights from the 1999-2004 NHANES Data

Introduction: Diabetic foot ulcers (DFU) are serious complications of diabetes. These ulcers significantly increase the risk of amputations. Many studies have examined how blood heavy metals affect insulin secretion in diabetes. However, research linking blood heavy metal exposure to DFU is limited. This study aims to explore the connection between blood heavy metal exposure and DFU in people with diabetes. Methods: This cross-sectional study used data from the 1999-2004 cycle of the National Health and Nutrition Examination Survey (NHANES). Researchers measured blood levels of lead (Pb) and cadmium (Cd) using inductively coupled plasma mass spectrometry (ICP-MS). Four logistic regression models assessed the relationship between blood heavy metals and the prevalence of DFU. The models adjusted for potential confounding factors. Additionally, smooth curve fitting and piecewise regression analyses were conducted to investigate the correlation further. Subgroup analyses and interaction tests helped evaluate consistency across the general population. Results: A total of 1664 participants aged 40 years or older with diabetes were included in the final analysis. The average age is 64.66 +/- 11.79 years, with 52.52% being male and 47.48% being female. Among these individuals, 135 (8.11%) were diagnosed with DFU. Statistical modeling revealed a significant positive correlation between blood cadmium (Cd) levels and the prevalence of DFU. Specifically, model 4, which was the fully adjusted model, indicated that for each unit increase in blood Cd level, there was a corresponding 64% increase in DFU prevalence [OR = 1.64; 95% CI (1.42-1.89), p = 0.004]. Further analysis through smooth curve fitting demonstrated a significant linear relationship between blood Cd levels and DFU prevalence. Conclusions: This study identified a positive correlation between blood cadmium (Cd) levels and the prevalence of DFU. These results suggest that monitoring blood Cd levels in patients with diabetes during follow-up may be important for preventing the development of DFU. However, further prospective studies are necessary to provide additional evidence.