Association of Arsenic and Nickel with Markers of Insulin Resistance and Beta Cell Dysfunction: A Case-Control Study in Indo Gangetic Plain

Abstract

Environmental exposure to toxic metals/metalloids (TM) has been linked to type 2 diabetes mellitus (T2DM) via mechanisms involving insulin resistance and beta cell dysfunction, especially in regions with significant industrial and agricultural activities. This study assessed the relationship between serum toxic element levels and glycemic markers, including HbA1c, insulin resistance (HOMA-IR), and beta cell function (HOMA-β%). In total, 783 participants (480 T2DM patients and 303 controls) were recruited. TM (Ni, As, Al, Pb, Cd, and Hg) was quantified using inductively coupled plasma mass spectrometry. HbA1c was measured using ion exchange high-performance liquid chromatography, while fasting insulin and glucose levels were measured using a Cobas 6000 Roche autoanalyzer to calculate HOMA-IR and HOMA-β%. Among the tested TM, As (72.2%) and Ni (66.2%) were the most prevalent and associated with T2DM. On multivariate analysis, Ni and As levels were significantly positively correlated with HbA1c (Ni: β = 0.13, As: β = 0.16) and IR (Ni: β = 0.31, As: β = 0.24), and negatively correlated with β-cell function (Ni: β = -0.09, As: β = -0.19). A significant decline in beta cell function (Ni: Q1:55.96, Q4:34.27; As: Q1:58.61, Q4:27.88) and increased IR (Ni: Q1:2.75, Q4:3.97; As: Q1:2.77, Q4:3.76) was observed across exposure quartiles. Nonfiltered water consumption and smoking were associated with higher levels of Ni, As, and IR. The risk (adjusted odds ratio) of T2DM increased 2.18-fold and 6.81-fold with Ni and As exposure, respectively. The district with the highest exposure (Bahraich) to Ni (82%) and As (88%) had the highest prevalence (82%) of T2DM among the study population. Arsenic and nickel exposure are strongly associated with impaired glycemic markers in T2DM and correspond to drinking water in the Indo-Gangetic Plain. Smoking was also associated with high Ni and As levels.

Keywords: Arsenic; Beta cell dysfunction; Insulin resistance; Nickel; Non-filtered water; Smoking; Toxic metals; Type 2 diabetes mellitus.