Cardiovascular disease in type 1 diabetes: A review of epidemiological data and underlying mechanisms.

Cardiovascular disease (CVD) is highly prevalent in patients with type 1 diabetes (T1D) and a major cause of mortality. CVD arises earlier in life in T1D patients and is responsible for a significant reduction of at least 11 years' life expectancy. Also, the incidence of CVD is much more pronounced in patients with T1D onset at an earlier age. However, the factors responsible for increased atherosclerosis and CVD in T1D are not yet totally clarified. In addition to the usual cardiovascular (CV) risk factors, chronic hyperglycaemia plays an important role by promoting oxidative stress, vascular inflammation, monocyte adhesion, arterial wall thickening and endothelial dysfunction. Diabetic nephropathy and cardiac autonomic neuropathy are also associated with increased CVD in T1D. In fact, the CVD risk remains significantly increased even in well-controlled T1D patients who have no additional CV risk factors, indicating that other potential factors are likely to be involved. Hypoglycemia and glucose variability could enhance CV disease by promoting oxidative stress, vascular inflammation and endothelial dysfunction. Furthermore, even well-controlled T1D patients show significant qualitative and functional abnormalities of lipoproteins that are likely to be implicated in the development of atherosclerosis and premature CVD. In addition, recent data suggest that a dysfunctional immune system, which is typical of autoimmune T1D, might also promote CVD possibly through inflammatory pathways. Moreover, overweight and obese T1D patients can manifest additional CV risk through pathophysiological mechanisms resembling those observed in type 2 diabetes (T2D).