The present observations may suggest further interventions in order to improve the outcome of COVID-19 in people affected by diabetes. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.. malignancy conditions. DNA methylation, besides being considered as a biomarker to predict the risk of obesity and T2D, has been suggested also as a target for dietary and pharmacological treatments. The present observations may suggest further interventions in order to improve the end result of COVID-19 in people affected by diabetes. and non-enzymatic glycation of albumin, showing that the number of glucose molecules that react with the lysine residues of albumin are directly related to the or (plasma) glucose levels . Considering now the occurrence of a non-enzymatic glycation of ACE2, its possible pathogenetic role in changing the protein tertiary structure in terms of amino acid (mostly lysine) available to be glycated, needs to be taken into consideration. Looking at the molecular structure (RCSB PDB protein Data Lender id: 6LGZ, DOI: https://doi.org//10.2210/pdb6LZG/pdb), in a single ACE2 molecule, 34 lysine residues are present in the extracellular portion, and at least one of these is co-involved in a fundamental hydrogen-bond interaction with the SARS-CoV-2 receptor binding domain name (RBD) . In diabetes disease also immunoglobulins (IGG) PECAM1 are exposed to high glucose concentrations; utilizing a MALDI/MASS Spectrometry approach we have exhibited that the number of glucose molecules condensed on IGG are related to the glucose levels and that in the case of poorly controlled diabetes, 20 glucose molecules react non-enzymatically with the lysine residues of IGG . Further experiments on IGG with mass spectrometry and computer-molecular modelling have evidenced that this Fab fragments are more prone to attack by ARRY-380 (Irbinitinib) glucose, particularly in the light and heavy variable regions . So, in persons with diabetes the immune deficiencies observed could be due to an extensive glycation of Fab fragment, thus inhibiting the process of molecular acknowledgement between antibody and antigen; this mechanism is usually consistent with the severe inflammatory state of patients with diabetes affected by COVID-19. Taking into consideration other clinical findings regarding co-morbidities during the epidemic diffusion in China, surveys of malignancy patients affected by COVID-19 indicated that lung adenocarcinoma (LUAD) was the most frequent tumour type, and such patients presented more severe symptoms , . Chai et al.  in a bioinformatic evaluation of genetic alteration, RNA expression, and DNA methylation of ACE2 across over 30 tumours, have suggested a link between variations of ACE2 receptors and propensity to SARS-CoV-2 contamination and COVID-19 severity. Regarding the specific mechanisms involved, the study highlighted the fact that ARRY-380 (Irbinitinib) although ACE2 expression is usually upregulated in several cancers, including LUAD, the upregulation is not the result of a genetic variations, but rather is due to epigenetic disorders including methylation . Moreover, the authors suggest that other mechanisms, including glycosylation  could be involved. We here hypothesize that this worse end result of COVID-19 in people with diabetes could be related, at least in part, to the two mechanisms already suggested for malignancy patients, specifically methylation and glycosylation, and in addition to the non-enzymatic glycation as we have discussed above, that could trigger the activity of ACE2. These considerations arise also from the knowledge that diabetes has a rigid link with DNA methylation of genes involved in islet beta-cell function, as well as in insulin resistance of peripheral tissues such as liver, muscle mass, and adipose tissue ; moreover the DNA methylation appears as a non-permanent condition, linked also to degree of diabetes control, and a potential target for diabetes ARRY-380 (Irbinitinib) control and therapy evaluation , . DNA methylation, besides being considered as a biomarker to predict the risk of obesity and T2D, has been suggested also as a target for dietary and pharmacological treatments . On the other side, glycation processes represent one of the most investigated milestones in pathogenesis, development and therapeutic target of diabetes , . The present observations may suggest further interventions.