Comment on risk factors differ by first manifestation of cardiovascular disease in type 1 diabetes: The impact of microvascular complications

Miller et al investigate the risk factors involved in First Manifestation of Cardiovascular Disease in Type1 Diabetes. Surprisingly in this paper no evaluation was performed about the presence of diabetic retinopathy (DR) and neuropa- thy (DN) in the population included in the study. It is well known that in type 1 diabetes microvascular complications burden might be associated with all cause mortality and cardiovascular events, and regarding DR this significant correlation remained after adjusting for traditional CV risk factors. Otherwise DN, in particular autonomic DN, regulates inflammation, one of the main mechanisms involved in pathogenesis of macrovascular complications. The modula- tion and the improvement of Sympatho-vagal balance produce a significant reduction of the markers of inflammation. For example calcium score, measure of atherosclerotic burden, is associated with both DR and DN [4,5] and vascular calcification is linked to DN. Previously we showed, although in type 2 diabetes, that diabetic subjects have a predominantly calcific plaque phenotype at the level of Minimum Lumen Area of culprit segment with less lipid quadrants and a smaller lipid arc. It should support the potential involvement of other mechanisms in the pathogenesis of macrovascular complications in diabetes. Furthermore diabetic subjects exhibit at the time of first acute coronary event, a better collateral development towards the culprit vessel despite more severe coronary atherosclerosis than non-diabetic subjects. Therefore I hypothesize that in diabetes, and in particular in type 1 diabetes with microvascular complications, there is an early development of cardiovascular atherosclerosis with the formation of collateral vessels, as mechanism of adaptation, that can resemble what happens in the DR with retinal neovascularization, and the occurrence of first cardiovacular event might be the consequence of a breakdown of this equilibrium. It could be the consequence of the progression of neuropathy. As it has been already demonstrated for another mediator as erythropoietin [7], it is conceivable that DN could impair the production of growth factor as Vascular Endothelial Growth Factor (VEGF) with a consequent loss of the development of collateral vessels, and at the same time might induce an overexpression of inflammation, through the impairment of a mechanism defined inflammatory reflex.