Association and risk of circulating inflammatory markers with hyperglycemia in coal-burning arsenicosis

Several lines of evidence support a significant relationship between exposure to arsenic and diabetes. However, the underlying pathophysiological mechanisms remain incompletely elucidated.

This study examined the association and risk of circulating inflammatory mediators with hyperglycemia in coal-induced arsenicosis.

A cross-sectional study was conducted in the typical coal-burning area in which arsenicosis is endemic in Xingren County, Guizhou, China. A total of 299 arsenicosis subjects and 137 non-arsenic exposed volunteers were recruited for the present study. Participant's hyperglycemia-related parameters, including fasting blood glucose (FBG), fasting serum insulin (FINS), homeostasis model assessment for both insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β), as well as circulating inflammatory biomarkers i.e., Interleukins-1β (IL-1β), IL- 2, IL - 6, IL-10, IL- 17, IL-18 and TNF-α), were determined and analyzed after completing questionnaire investigation and physical examination.

The results clearly showed that coal-burning arsenic exposure was significantly associated with hyperglycemia-related outcomes. Specifically, arsenicosis subjects from the coal-burning endemic area showed a higher level of FBG (median 5.87 mmol/L vs. 4.65 mmol/L) and increased prevalence of hyperglycemia (26.76% vs.16.79%) than reference subjects from the non-arsenic endemic area. Increased HOMA-IR (median 1.93 vs.1.44) and declined HOMA-β (median 96.23 vs. 84.91) were also noted in arsenicosis subjects. Moreover, arsenic exposure was significantly associated with the increased risk of hyperglycemia (adjusted OR = 2.32, 95% CI: 1.37,3.93). In addition, a positive association between arsenic exposure and inflammatory response was observed, and the alteration in circulating inflammatory markers were found to be significantly associated with hyperglycemia-related parameters. Meanwhile, there was a positive relationship between elevated circulating IL-1β, IL-18, IL-6, as well as decreased IL-10 and the increasing risk of arsenic-induced hyperglycemia [adjusted OR = 2.19 (95% CI: 1.26, 3.13);1.13 (95%CI: 1.08, 1.37); 1.19 (95% CI: 1.13, 1.56); 1.15(95% CI: 1.05, 1.36); respectively]. Path analysis further revealed that the mediating effect of IL-1β and IL-18 on the relationship between arsenic exposure and hyperglycemia was closely associated with pancreatic β-cell dysfunction, while those of IL-6 and IL-10 on the association between arsenic exposure and hyperglycemia were partially through insulin resistance.

This population-based study indicated that arsenic exposure has a clear disruptive effect on glucose homeostasis, and an elevated inflammatory response was implicated in the risk of arsenic-induced hyperglycemia.