Abstract P170: The Association of Urinary Cadmium and Zinc With Lower Extremity Amputations. Evidence From the Strong Heart Study

Abstract

Background: Cadmium is a cardiotoxic divalent metal that accumulates in the liver and kidney. It resembles the essential metal zinc, replacing it in numerous enzymes and proteins. Zinc plays a major role in insulin function. Glucose dyshomeostasis increases the loss of zinc through the urine. Cadmium has been associated with peripheral artery disease and critical limb ischemia, conditions that lead to limb amputations. Chelation treatment with edetate disodium, an agent that facilitates the excretion of cadmium from the body, was beneficial for individuals with critical limb ischemia and diabetes in several small studies. This study evaluated the association of urinary levels of cadmium and zinc with amputations in a population with a high burden of diabetes from Arizona, Oklahoma, North Dakota and South Dakota. Hypothesis: We hypothesize that urinary cadmium and zinc levels are related to prevalent amputations in the SHS cohort. Methods: We included 2,724 participants from the Strong Heart Study, a population-based cohort study in 12 American Indian communities, recruited in 1989-1991 and followed for amputations through 1998-1999. Trained staff identified amputations of the lower extremity through visual examination at the baseline visit. We censored traumatic amputations. Baseline metal levels in spot urine samples were divided by urinary creatinine to account for urine dilution. Results: Mean age was 56.4 years, 41.5% participants were male, and 42% had diabetes. We identified a total of 35 (1.3%) amputations of the lower extremities during the study period. Median urinary levels were 0.97 μg/g for cadmium and 0.56 mg/g for zinc. Higher levels of urinary cadmium and zinc were positively associated with the presence of amputations. The odds ratios of prevalent amputations for an IQR of cadmium and zinc distribution were 1.54 (1.00, 2.38) and 2.24 (1.48, 3.39), respectively, in models adjusted for sociodemographic, lifestyle (tobacco and alcohol intake), and other factors (BMI, hypertension and diabetes status, HDL and LDL-cholesterol, and estimated glomerular filtration rate). The associations remained after further adjustment for fasting plasma glucose levels. Urinary cadmium and zinc levels were positively correlated (r=0.24, P<0.001). Conclusions: Urinary cadmium and zinc were positively associated with the presence of lower extremity amputations in American Indian adults with a high burden of diabetes. These results support the current evidence of cadmium as a cardiometabolic risk factor, and the potential role of impaired zinc metabolism, reflected as increased urinary zinc excretion, in vascular complications of diabetes.