Several epidemiological and prospective studies suggest that an early intensive control of hyperglycaemia is able to decrease the risk of diabetic micro- and macro-vascular complications. A growing body of experimental evidence supports the concept that the risk for diabetes complications may be linked to oxidative stress, non-enzymatic glycation of proteins, epigenetic changes, and chronic inflammation, laying the foundation for the “metabolic memory” theory. From a clinical point of view, this theory supports the need for a very early aggressive treatment, with the goal of normalizing metabolic control as soon as possible. It may also prove beneficial to introduce therapeutic agents that are able to reduce reactive species and glycation, in addition to presenting better control of glucose levels in patients with diabetes, in order to minimize long-term diabetes complications. In this review, we evaluate the effect of glucose intake and metabolism in the light of this theory.

Atherosclerosis is one of the main complications of diabetes involving multiple causative factors. Dysfunction of the vascular endothelium is a hallmark of most conditions that are associated with both diabetes and atherosclerosis. Although the pathological link between diabetes and atherosclerosis is well-established, better comprehension of the underlying mechanisms is of utmost importance to identify novel potential molecular targets. It is difficult to separate the effects of hyperglycaemia from those of other atherogenic factors: recent evidence shows that they share many common mechanisms, such as endothelial activation and inflammation, mitochondrial oxidative stress, changes in extracellular matrix components and disruption of cellular defence systems. The plausible hypothesis of the ‘common soil’ between diabetes and atherosclerosis seems to be born from a unique ‘ancestor’: the nuclear factor κB, a transcription factor able to guide multiple molecular processes. It seems that this master regulator triggers either some hyperglycaemia-induced effects on the endothelial function, or the expression of certain microRNAs (in particular miR-126, -21 and miR-146a-5p) involved in favouring atherosclerosis. Here, we review the latest evidence and proposed mechanisms, aiming to understand the link between diabetes and atherosclerosis.

OBJECTIVE: Hyperglycemia and hypoglycemia currently are considered risk factors for cardiovascular disease in type 1diabetes. Both acute hyperglycemia and hypoglycemia induce endothelial dysfunction and inflammation, raising the oxidative stress. Glucagon-like peptide 1 (GLP-1) has antioxidant properties, and evidence suggests that it protects endothelial function. RESEARCH DESIGN AND METHODS: The effect of both acute hyperglycemia and acute hypoglycemia in type 1 diabetes, with or without the simultaneous infusion of GLP-1, on oxidative stress (plasma nitrotyrosine and plasma 8-iso prostaglandin F2alpha), inflammation (soluble intercellular adhesion molecule-1 and interleukin-6), and endothelial dysfunction has been evaluated. RESULTS: Both hyperglycemia and hypoglycemia acutely induced oxidative stress, inflammation, and endothelial dysfunction. GLP-1 significantly counterbalanced these effects. CONCLUSIONS: These results suggest a protective effect of GLP-1 during both hypoglycemia and hyperglycemia in type 1 diabetes.

Obesity is one of the major risk factors for the development of both impaired glucose tolerance (IGT, or prediabetes) and type 2 diabetes (T2D), and its prevalence worldwide drives toward an increased rate of cardiovascular morbidity and mortality. Given the estimations of the World Health Organization (WHO) and the recommendation of the Diabetes Prevention Program (DPP), where IGT and diabetes are considered as risk factors for the development of cardiovascular complications and obesity, the development of diabetes should be treated because of its potential reversibility. In this view, several interventions such as diet, lifestyle changes, and pharmacological treatment are effective, including bariatric metabolic surgery (BMS), which is the most incisive way to efficiently lower body weight. In this review, we sought to summarize some of the major aspects linked to diabetes prevention in overweight/obesity, focusing on the use of surgery; we also attempted to elucidate molecular pathways involved in a variety of obesity-induced processes able to favor the progression of chronic diseases, such as diabetes and its complications.

Diabetic status is characterized by chronic low-grade inflammation and an increased burden of senescent cells. Recently, the senescence-associated secretory phenotype (SASP) has been suggested as a possible source of inflammatory factors in obesity-induced type 2 diabetes. However, while senescence is a known consequence of hyperglycaemia, evidences of SASP as a result of the glycaemic insult are missing. In addition, few data are available regarding which cell types are the main SASP-spreading cells in vivo. Adopting a four-pronged approach we demonstrated that: i) an archetypal SASP response that was at least partly attributable to endothelial cells and macrophages is induced in mouse kidney after in vivo exposure to sustained hyperglycaemia; ii) reproducing a similar condition in vitro in endothelial cells and macrophages, hyperglycaemic stimulus largely phenocopies the SASP acquired during replicative senescence; iii) in endothelial cells, hyperglycaemia-induced senescence and SASP could be prevented by SOD-1 overexpression; and iiii) ex vivo circulating angiogenic cells derived from peripheral blood mononuclear cells from diabetic patients displayed features consistent with the SASP. Overall, the present findings document a direct link between hyperglycaemia and the SASP in endothelial cells and macrophages, making the SASP a highly likely contributor to the fuelling of low-grade inflammation in diabetes.