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Ceriello A.,Insititut dInvestigacions Biomediques August Pi i Sunyer IDIBAPS
Vascular Pharmacology | Year: 2012

Large randomized studies have established that early intensive glycemic control reduces the risk of diabetic complications, both micro and macrovascular. However, epidemiological and prospective data support a long-term influence of early metabolic control on clinical outcomes. This phenomenon has recently been defined as "metabolic memory." Potential mechanisms for propagating this "memory" may be the production of reactive species unrelated to the presence of hyperglycemia, depending on the previous production of AGEs which can maintain RAGE over-expression, on the level of glycation of mitochondrial proteins and on the amount of mtDNA produced, all conditions able to induce an altered gene expression which may be persistent even when glycemia is normalized. Clinically, the emergence of this "metabolic memory" suggests the need for a very early aggressive treatment aiming to "normalize" the metabolic control and the addition of agents which reduce cellular reactive species and glycation in addition to normalizing glucose levels in diabetic patients in order to minimize long-term diabetic complications. © 2012 Elsevier Inc. Source


Ceriello A.,Insititut dInvestigacions Biomediques August Pi i Sunyer IDIBAPS
European Journal of Cardiovascular Prevention and Rehabilitation | Year: 2010

Large randomised studies have established that early intensive glycaemic control reduces the risk of diabetic complications, both microvascular and macrovascular. However, epidemiological and prospective data support a long-term influence of early metabolic control on clinical outcomes. This phenomenon has recently been defined as 'metabolic memory'. Furthermore, evidence suggests that 'glucose variability' may also be an independent risk factor for cardiovascular complications in diabetes. Studies suggest that all these different situations of hyperglycaemia share a common pathogenetic mechanism, increased oxidative stress, producing an endothelial dysfunction. The therapeutic challenge derived from these evidences is a need not only for an early tight glycaemic control, but also for maintaining glycaemia within a strict normal narrow range. © 2010 The European Society of Cardiology. Source


Ceriello A.,Insititut dInvestigacions Biomediques August Pi i Sunyer IDIBAPS | Esposito K.,2nd University of Naples | Ihnat M.,The University of Oklahoma Health Sciences Center | Thorpe J.,The University of Oklahoma Health Sciences Center | Giugliano D.,2nd University of Naples
Diabetic Medicine | Year: 2010

Objective To investigate the possibility of reversing endothelial dysfunction and inflammation by glucose normalization, antioxidants and insulin per se, in different subgroups of Type 1 diabetic patients. Methods Three subgroups of Type 1 diabetic patients were studied: patients within 1 month of diagnosis (subgroup 1); patients with approximately 5 years' disease duration and with glycated haemoglobin (HbA1c) ≤ 7.0% (subgroup 2) or > 7.0% since diagnosis (subgroup 3). Participants underwent four procedures: 2-h hyperglycaemic clamp followed by: (A) 12 h near-normalization of blood glucose, with the addition of vitamin C during the last 6 h; (B) 12-h vitamin C and near-normalization of blood glucose for the last 6 h; (C) both vitamin C and near-normalization of blood glucose for 12 h; (D) hyperglycaemic- hyperinsulinaemic clamp for 12 h, with the addition of vitamin C during the last 6 h. Results After 2 h of hyperglycaemia, markers of endothelial dysfunction, nitrotyrosine, 8-iso prostaglandin F2α, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, interleukin (IL)-6 and IL-18 were increased in all the subgroups. Levels were normalized, at all time points, by treatments A, B and C in the subgroups 1 and 2. In the third subgroup, levels were normalized only by the simultaneous normalization of blood glucose and vitamin C treatment. During treatment D, the levels were improved at 6 h in all the subgroups, but normalized at 12 h only after vitamin C in subgroups 1 and 2, but not in subgroup 3. Conclusions This study suggests that different subgroups of Type 1 diabetic patients react identically to acute hyperglycaemia and insulin, but differently to glucose normalization. © 2010 Diabetes UK. Source


Ceriello A.,Insititut dInvestigacions Biomediques August Pi i Sunyer IDIBAPS | Cremasco F.,Eli Lilly and Company | Romoli E.,Eli Lilly and Company | Rossi A.,Eli Lilly and Company | Gentilella R.,Eli Lilly and Company
Expert Opinion on Pharmacotherapy | Year: 2012

Introduction: Insulin lispro protamine suspension (ILPS) is a protamine-based insulin lispro formulation that allows 24-h coverage while limiting the number of daily injections. ILPS was developed to be the basal insulin component of premixed biphasic formulations with insulin lispro, i.e., the lispro/ILPS 25/75 and 50/50 mixed compounds, but has recently also been marketed as a basal insulin analog formulation, with an indication for the therapy of diabetic patients. Areas covered: This article reviews the available literature on pharmacokinetics/pharmacodynamics (PK/PD), efficacy and safety of ILPS administered as basal insulin, or in premixed biphasic formulations, in patients with type 1 and type 2 diabetes mellitus. Expert opinion: The results of this review suggest that ILPS may be associated with a favorable timeaction profile, basal and postprandial glycemic control, and efficacy in terms of rates of patients reaching glycosylated hemoglobin targets; an increased risk of hypoglycemic episodes, compared to other basal insulins, seems to be related to the percentage of patients upgrading from once- to twice-daily injections. This increased risk might be linked with the concomitant use of insulin secretagogues in patients on higher daily dosages and is generally not observed in patients using one injection of ILPS a day. Thus, ILPS can be considered a valid option both as basal insulin and as basal component of the actual premixed formulations of lispro for the therapy of diabetic patients. © 2012 Informa UK, Ltd. Source


Testa R.,INRCA IRCCS National Institute | Genovese S.,IRCCS Gruppo Multimedica | Ceriello A.,Insititut dInvestigacions Biomediques August Pi i Sunyer IDIBAPS | Ceriello A.,Research Center Biomedica En Red Of Diabetes
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2014

Quality of nutrition plays a central role in illnesses such as diabetes and its complications. Dietary and lifestyle habits may have a strong impact, either worsening or improving the evolution of diabetes mellitus. Some factors, such as obesity, worsen the illness, causing chronic inflammation, lipid metabolic disorder, accelerated atherosclerosis, increased risk for thrombosis, hypertension, hyperinsulinemia, insulin resistance, and cellular senescence. Some other nutritional components, however, have an opposite effect, probably increasing antioxidant defense. RECENT FINDINGS: The effects of nutritional factors on cellular senescence in diabetic patients are described in this review. In particular, we discuss some of the nutritional causes of cellular senescence in diabetes mellitus and focus on different nutraceutical compounds that can affect cellular senescence. Furthermore, relevant mechanisms of action are also described. SUMMARY: Diet and nutraceutical factors have important effects on diabetes mellitus. Some molecules, which improve antioxidant defense, may counteract cellular senescence. A good lifestyle with physical activity and good weight control can improve the quality of life in diabetic people; on the contrary, obesity and vitamin deficiencies may worsen the evolution of this illness, even inducing cellular senescence.Copyright © Lippincott Williams &Wilkins. Source

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