Background:
Diabetes mellitus is a chronic metabolic disease, characterized by increased blood glucose levels and associated with severe cardio- and cerebrovascular damage. It was shown that aircraft noise exposure results in oxidative stress-mediated cardiovascular complications with a central role for NADPH oxidase (NOX-2) activation and uncoupling of endothelial nitric oxide synthase (eNOS). Although epidemiological data suggest that aircraft noise increases the incidence of metabolic diseases such as diabetes, both cardiovascular risk factors are still independently investigated. Therefore, in the present study, we investigated the synergistic/additive effects of aircraft noise exposure on cardiovascular complications in 2 different murine models of diabetes mellitus.

Methods and Results:
C57/Bl6 mice were treated with streptozotocin (i.p. injections, 50 mg/kg/d for 5 days) to induce type I diabetes mellitus or fed a high-fat diet (Western Diet, 20 weeks) to induce a type II diabetes mellitus. To determine synergistic/additive effects of aircraft noise, we exposed C57/Bl6 control mice and both diabetes models to aircraft noise (maximum sound pressure level of 85 dB(A), average sound pressure level of 72 dB(A)) for the last 4 days of the treatment period. We could show that noise exposure increases plasma glucose levels and modifies the insulin signaling cascade in HFD fed mice, where insulin production was increased as a compensatory mechanism to overcome the inadequate glycemic control. In addition, traffic noise exposure aggravated the diabetes-induced elevation of systolic blood pressure and endothelial dysfunction in the aorta and small resistant vessels (a. mesenterica). Endothelial dysfunction was associated with increased formation rates of aortic and cardiac reactive oxygen species as a consequence of increased expression of NOX-2, accompanied by increased levels of 3‑nitrotyrosine positive proteins. Finally, we observed the additive effect of aircraft noise exposure on increased production of mitochondrial reactive oxygen species and impaired mitochondrial function.

Conclusion:
Here we present novel data of interaction between diabetes mellitus associated vascular complications and aircraft noise exposure. Our data suggest that noise exposure has synergistic/additive effects not only on insulin signaling but also on endothelial dysfunction, oxidative stress and mitochondrial homeostasis, especially in patients at high cardiovascular risk, with pre-existing cardio-metabolic disease such as diabetes mellitus. The present findings offer the unique opportunity to better understand the genesis of diabetes mellitus as well as the additive effects of aircraft noise exposure on cardiovascular complications in mice with pre-existing diabetic phenotypes.

Support or Funding Information: Boehringer Ingelheim Stiftung, Research Consortium „Novel and neglected risk factors“.