Toxicology and applied pharmacology

Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model.

PMID 25454026


Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM2.5 exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24h/day, 7days/week, for a total of 16weeks. The average concentrations (mean [SD]) of PM2.5 in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05]μg/m(3), respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P<0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P<0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation.