Background: Diabetes mellitus is a chronic metabolic disorder in which the production or response to insulin is impaired. This disease is characterized by increased blood glucose levels and is associated with severe cardiovascular and neurological complications. One of emerging environmental risk factors is traffic noise. We have previously shown that aircraft noise exposure provokes oxidative stress-mediated cardiovascular damage with an essential role for NADPH oxidase (NOX-2) activation and uncoupling of endothelial nitric oxide synthase (eNOS). Although epidemiological data proposes that traffic noise rises the incidence of metabolic diseases such as obesity or diabetes, both risk factors were studied separately. Therefore, we investigated the effects of aircraft noise exposure on cardiovascular complications in 3 different murine models of diabetes mellitus.

Methods and Results: C57/BL6 mice were treated with streptozotocin (STZ, i.p. injections, 50 mg/kg/d for 5 days) to induce type I diabetes mellitus or treated with S961 (subcutaneous osmotic minipumps, 0.57 mg/kg/d for 7 days) or fed a high-fat diet (HFD, Western Diet, 20 weeks) to induce type II diabetes mellitus. To determine the effects of aircraft noise, we exposed control mice and diabetic mice 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 were able to show that aircraft noise exposure worsens the diabetes-induced increase of systolic blood pressure and impaires the endothelial function in aorta and small resistant vessels. Elevated blood pressure was associated with increased levels of endothelin 1 and 3-nitrotyrosine positive proteins. In addition, endothelial dysfunction was associated with increased superoxide formation in aortic and cardiac tissue caused by up-regulated expression of NOX-2, accompanied by elevated levels of 3‑nitrotyrosine positive proteins. Furthermore, we detected a synergistic effect of noise exposure on increased levels of mitochondrial reactive oxygen species in STZ and HFD models along with impaired mitochondrial function. Finally, inflammatory markers such as nuclear factor kappa—light-chain-enhancer of activated B cells (NF-κB) and intercellular adhesion molecule 1 (ICAM-1) significantly elevated in aortic tissue of noise exposed diabetic animals.      

Conclusion: Here, we investigated the interaction between diabetes mellitus associated cardiovascular complications and aircraft noise exposure. Our data suggest that aircraft noise exposure has synergistic effects on endothelial dysfunction, oxidative stress, mitochondrial homeostasis and inflammation notably in patients at greater cardiovascular risk, with prior cardio-metabolic disease such as diabetes mellitus. Our findings present a great opportunity to identify the molecular pathways that explain the genesis of type 1 and 2 diabtes mellitus and aircraft noise induced cardiovascular injury. Further experiments with aircraft noise exposure in patients suffering diabetes mellitus will be highly interesting in order to proof our findings.

Support or Funding Information: Boehringer Ingelheim Stiftung (BIS) - Research Consortium „Novel and neglected risk factors“, Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK).