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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.

Frontoni S.,University of Rome Tor Vergata | Di Bartolo P.,UO di Diabetologia | Avogaro A.,University of Padua | Bosi E.,Vita-Salute San Raffaele University | And 2 more authors.
Diabetes Research and Clinical Practice | Year: 2013

Alterations in glucose metabolism in individuals with diabetes have been considered for many years, as they appear at first glance, i.e., simply as hyperglycemia, and its surrogate marker, glycated hemoglobin (HbA1c), used both to estimate the risk of developing diabetic complications and to define the targets and measure the efficacy of diabetes treatments.However, over time diabetes-related glycemic alterations have been considered in more complex terms, by attempting to identify the role of fasting glycemia, postprandial glycemia and hypoglycemia in the overall assessment of the disease.This set of evaluations has led to the concept of glucose variability. Although intuitively easy to understand, it cannot be equally simply translated into terms of definition, measuring, prognostic and therapeutic impact. The literature available on glucose variability is extensive yet confused, with the only common element being the need to find out more on the subject.The purpose of this manuscript is not only to review the most recent evidence on glucose variability, but also to help the reader to better understand the available measurement options, and how the various definitions can differently be related with the development of diabetic complications. Finally, we provide how new and old drugs can impact on glucose variability. © 2013 Elsevier Ireland Ltd.

Yu P.C.,Chinese PLA General Hospital | Bosnyak Z.,Novo Nordisk AS | Ceriello A.,Insititut dInvestigacions Biomediques August Pi i Sunyer IDIBAPS
Diabetes Research and Clinical Practice | Year: 2010

Vascular complications are the leading cause of morbidity and mortality in type 2 diabetes. Cardiovascular disease is significantly more common in patients with type 2 diabetes than in non-diabetics, and accounts for more than two-thirds of deaths associated with the condition. Many physicians believe that hyperglycaemia is responsible, at least in part, for this additional risk. The benefit of improved glycaemic control on microvascular complications is well established and recent trials have attempted to clarify the role of glycaemic control on macrovascular outcomes. This article reviews the recent evidence from a post-interventional analysis of the UKPDS and the ACCORD, ADVANCE, VADT and HEART2D trials for an association between elevated blood glucose levels and vascular complications. The data suggest that improved glycaemic control has the potential to significantly reduce the risk of micro- and macrovascular disease when instigated early in the disease course. However, in more advanced diabetes, the benefits of improved control appear to be less evident. Recent studies have also suggested that controlling postprandial glucose may be an important component in the reduction of vascular complications. Taken together, these studies indicate that glycaemic control remains a key cornerstone in the management of type 2 diabetes. © 2010.

Ceriello A.,Insititut dInvestigacions Biomediques August Pi i Sunyer IDIBAPS | Ihnat M.A.,The University of Oklahoma Health Sciences Center
Diabetic Medicine | Year: 2010

Much attention has been paid recently to the possibility that oscillating glucose may superimpose on glycated haemoglobin (HbA1c) in determining the risk for diabetes complications. Furthermore, recent evidence suggests that glucose variability, particularly if accompanied by frequent hypoglycaemic episodes, may adversely alter the prognosis of acutely ill patients. In vitro and animal studies confirm that oscillating glucose is more dangerous than stable constant high glucose, particularly in activating the pathways involved in the pathogenesis of diabetes complications. The production of free radicals, accompanied by an insufficient increase in intracellular antioxidant defences, seems to account for this phenomenon. In humans, studies also confirm that fluctuating glucose levels produce an increase in free radicals as well as endothelial dysfunction, and that these changes are greater than those produced by stable high glucose. Avoiding glucose fluctuations in diabetic patients and in crtically ill patients seems to be an emerging therapeutic challenge. © 2010 Diabetes UK.

Ceriello A.,Insititut DInvestigacions Biomediques August Pi i Sunyer IDIBAPS
International Journal of Clinical Practice | Year: 2010

The prevalence of type 2 diabetes across the world has been described as a global pandemic. Despite significant efforts to limit both the increase in the number of cases and the long-term impact on morbidity and mortality, the total number of people with diabetes is projected to continue to rise and most patients still fail to achieve adequate glycaemic control. Optimal management of type 2 diabetes requires an understanding of the relationships between glycosylated haemoglobin (HbA 1c), fasting plasma glucose and postprandial glucose (the glucose triad), and how these change during development and progression of the disease. Early and sustained control of glycaemia remains important in the management of type 2 diabetes. The contribution of postprandial glucose levels to overall glycaemic control and the role of postprandial glucose targets in disease management are currently debated. However, many patients do not reach HbA 1C targets set according to published guidelines. As recent data suggest, if driving HbA 1C down to lower target levels is not the answer, what other factors involved in glucose homeostasis can or should be targeted? Has the time come to change the treatment paradigm to include awareness of the components of the glucose triad, the existence of glucose variability and their potential influence on the choice of pharmacological treatment? It is becomingly increasingly clear that physicians are likely to have to consider plasma glucose levels both after the overnight fast and after meals as well as the variability of glucose levels, in order to achieve optimal glycaemic control for each patient. When antidiabetic therapy is initiated, physicians may need to consider selection of agents that target both fasting and postprandial hyperglycaemia. © 2010 Blackwell Publishing Ltd.

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.

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.

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.

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.

Esposito K.,The Second University of Naples | Ceriello A.,Insititut dInvestigacions Biomediques August Pi i Sunyer IDIBAPS | Giugliano D.,The Second University of Naples
Endocrine | Year: 2013

Uncertainties abound in clinical management of type 2 diabetes. Sources of uncertainty specific to type 2 diabetes originate from the panoply of glycemic (HbA1c) targets, the complexity of drug therapy, the ideal sequence of drugs after metformin failure, the possible harms of anti-hyperglycemic drugs, the outcomes of treatment (surrogate versus clinical) and the hierarchy of risk factors to treat in order to prevent the vascular complications. Ironically, multiple treatment guidelines and algorithms periodically released to improve guidance may generate confusion into clinicians. Moreover, treatment algorithms cannot be truly evidence-based because of a lack of studies comparing all available treatment combination options. Personalized therapy essentially identifies patients who could have major benefits from the therapy as compared with other patients. Personalized medicine for type 2 diabetic has the potential to improve the quality health-care practice of diabetes management, but specific research is needed. © 2013 Springer Science+Business Media New York.

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