IJMS, Vol. 26, Pages 9208: Enhanced Kidney Damage in Individuals with Diabetes Who Are Chronically Exposed to Cadmium and Lead: The Emergent Role for β2-Microglobulin

International Journal of Molecular Sciences doi: 10.3390/ijms26189208

Authors:
Soisungwan Satarug
David A. Vesey
Donrawee Waeyeng
Tanaporn Khamphaya
Supabhorn Yimthiang

Elevated levels of circulating β2-microglobulin (β2M) are linked to an increased risk of hypertension and mortality from diabetes. The present study tests the hypothesis that the environmental pollutants, cadmium (Cd) and lead (Pb), by increasing plasma β2M levels, promote the development of hypertension and progression of diabetic kidney disease. Herein, we analyzed data from a Thai cohort of 72 individuals with diabetes and 65 controls without diabetes who were chronically exposed to low levels of Cd and Pb. In all subjects, serum concentrations of β2M inversely correlated with the estimated glomerular filtration rate (eGFR) (r = −0.265) and directly with age (r = 0.200), fasting plasma glucose (r = 0.210), and systolic blood pressure (r = 0.229). The prevalence odds ratio (POR) for hyperglycemia increased 7.7% for every 1-year increase in age and increased 3.9-fold, 3.1-fold, and 3.7-fold in those with serum β2M levels ≥ 5 mg/L, Cd/Pb exposure categories 2 and 3, respectively. The POR for hypertension increased 2.9-fold, 3-fold, and 4-fold by hyperglycemia (p = 0.011), Cd/Pb exposure categories 2 and 3. The POR for albuminuria increased 3.5-fold by hyperglycemia. In conclusion, kidney damage, evident from albuminuria, was particularly pronounced in participants with diabetes who had a serum β2M above 5 mg/L plus chronic exposure to low-dose Cd and Pb. For the first time, through a mediation analysis, we provide evidence that links Cd exposure to the SH2B3-β2M pathway of blood pressure homeostasis in people with and without diabetes.

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