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