**4. Chronic obstructive pulmonary disease and diabetes** *mellitus* **related pathogenesis**

COPD and DM share relevant features in their genesis and course. Hypoxia, insulin resistance, oxidative stress and inflammation are the basis of a common pathogenesis. Concomitant factors such as tobacco, obesity and sleep disorders merge in endothelial dysfunction and atherosclerosis leading to a high cardiovascular risk of both conditions (Figure 1).

Inflammation is a well recognized phenomenon in COPD and DM pathogenesis. In COPD, inflammation and oxidative stress require an energy expenditure that exacerbate the preexisting hypoxia. In a parallel way, inflammatory cytokines exacerbate insulin resistance through diverse mechanisms. Impaired function of the type 1 insulin receptor substrate (IRS-1) is a key, direct mechanism. Thus, there is a chronic, subclinical inflammation at the background of COPD and DM. The question about its significance in patients with simultaneous COPD and DM is then arised. Being not fully clarified, we propose the following sequence of events: common COPD and DM related pathogenesis would start by hypoxia and insulin resistance followed by systemic inflammation, oxidative stress and a final coexistence of endothelial dysfunction and subsequent cardiovascular events.
