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Articles by A. Ceriello
Total Records ( 7 ) for A. Ceriello
  M. A. Ihnat , J. E. Thorpe and A. Ceriello
  Large randomized studies have established that early intensive glycaemic 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’ are the non-enzymatic glycation of cellular proteins and lipids, and an excess of cellular reactive oxygen and nitrogen species, in particular originated at the level of glycated-mitochondrial proteins, perhaps acting in concert with one another to maintain stress signalling. Furthermore, the emergence of this ‘metabolic memory’ suggests the need for very early aggressive treatment aiming to `normalize` glycaemic control and the addition of agents which reduce cellular reactive species and glycation in order to minimize long-term diabetic complications.
  A. Ceriello and S. Colagiuri
  Diabetes is a significant and growing concern, with over 246 million people around the world living with the disease and another 308 million with impaired glucose tolerance. Depending on the resources of different nations, intervention has generally focused on optimizing overall glycaemic control as assessed by glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) values. Nevertheless, increasing evidence supports the importance of controlling all three members of the glucose triad, namely HbA1c, FPG and postmeal glucose (PMG) in order to improve outcome in diabetes. As part of its global mission to promote diabetes care and prevention and to find a cure, the International Diabetes Federation (IDF) recently developed a guideline that reviews evidence to date on PMG and the development of diabetic complications. Based on an extensive database search of the literature, and guided by a Steering and Development Committee including experts from around the world, the IDF Guideline for Management of Postmeal Glucose offers recommendations for appropriate clinical management of PMG. These recommendations are intended to help clinicians and organizations in developing strategies for effective management of PMG in individuals with Type 1 and Type 2 diabetes. The following review highlights the recommendations of the guideline, the supporting evidence provided and the major conclusions drawn. The full guideline is available for download at
  P. J. Beisswenger , W. V. Brown , A. Ceriello , N. A. Le , R. B. Goldberg , J. P. Cooke , D. C. Robbins , S. Sarwat , H. Yuan , C. A. Jones and M. H. Tan
  Aim  To determine if a regimen with prandial + basal insulin compared with basal insulin attenuates post-meal inflammatory and glycative biomarkers in patients with Type 2 diabetes. Methods  This test-meal sub-study in the USA is from a previously reported clinical trial comparing the effect on glycaemic control of 24 weeks of thrice-daily pre-meal insulin lispro mix 50 (50% insulin lispro, 50% insulin lispro protamine suspension) or bedtime insulin glargine, both plus metformin. In the sub-study, glucose, insulin, triglycerides, high-sensitivity C-reactive protein, tumour necrosis factor α, interleukin-6, methylglyoxal and 3-deoxyglucosone were measured during the post-meal period of a mixed-meal breakfast at the final visit. Prandial + basal (n = 25) and basal (n = 21) insulin were administered at the same times as during the previous 24 weeks. Results  Post-meal, the prandial + basal insulin group had significantly higher insulin, lower glucose and triglycerides, as well as lower high-sensitivity C-reactive protein, tumour necrosis factor α and interleukin-6, than the basal insulin group. Glucose incremental area under the concentration curve significantly correlated with high-sensitivity C-reactive protein, tumour necrosis factor α, interleukin-6, methylglyoxal and 3-deoxyglucosone incremental area under the concentration curve. Insulin incremental area under the concentration curve correlated inversely with high-sensitivity C-reactive protein and tumour necrosis factor α incremental area under the concentration curve. However, after adjusting for glucose incremental area under the concentration curve, these inverse correlations were no longer significant. Triglyceride incremental area under the concentration curve was not correlated with any biomarker incremental area under the concentration curve. Conclusions  Controlling post-meal hyperglycaemia with prandial + basal insulin in patients with Type 2 diabetes attenuates meal-induced increases in high-sensitivity C-reactive protein, interleukin-6 and tumour necrosis factor α compared with basal insulin. The rise in post-meal glucose, but not triglycerides, significantly correlated with the rise in post-meal inflammatory and glycative biomarkers.
  A. Ceriello and M. A. Ihnat
  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.
  A. Ceriello , K. Esposito , M. Ihnat , J. Thorpe and D. Giugliano
  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.

  M. V. Chittari , P. McTernan , N. Bawazeer , K. Constantinides , M. Ciotola , J. P. O`Hare , S. Kumar and A. Ceriello
  Aim  In diabetes, endothelial dysfunction and an altered retinal blood flow have been reported and precede overt macrovascular and microvascular disease. Furthermore, an association between postprandial hyperglycaemia, retinopathy and cardiovascular disease has been observed.

Methods  Endothelial function and retinal vascular reactivity have been measured in baseline conditions in 10 healthy control subjects and 21 patients with Type 2 diabetes. In the patients with Type 2 diabetes, endothelial function and retinal vascular reactivity have been also measured every hour, for 4 h, during an oral glucose tolerance test. Endothelial function has been evaluated by measuring flow-mediated vasodilation of the brachial artery, while retinal vascular reactivity has been measured using a retinal vessel analyser, during a flicker.

Results  At 1 and 2 h after glucose ingestion, endothelial function decreased (P < 0.05), while retinal vascular reactivity increased, even at 3 h (P < 0.05), vs. the baseline values.

Conclusion  Our data highlight that acute hyperglycaemia impacts on endothelial function simultaneously at both macrovascular and at microvascular levels, inducing functional change, which could contribute towards explaining the clinical evidence of a strong association between postprandial hyperglycaemia, cardiovascular disease and retinopathy.

  R. Testa , F. Olivieri , C. Sirolla , L. Spazzafumo , M. R. Rippo , M. Marra , A. R. Bonfigli , A. Ceriello , R. Antonicelli , C. Franceschi , C. Castellucci , I. Testa and A. D. Procopio
  Objective  The key goal of diabetes management is to prevent complications. While the patho-physiological mechanisms responsible for diabetes complications have been extensively studied, at present it is impossible to predict which patient with diabetes could develop complications. In recent years, the role of leukocyte telomere length in the pathogenesis of cardiovascular disease and Type 2 diabetes has been investigated. However, studies aiming to investigate the role of telomeres in the development and progression of Type 2 diabetes, as well as diabetic complications, are still lacking. As a consequence, this study aimed to verify whether leukocyte telomere length is associated with the presence and the number of diabetic complications in a sample of patients with Type 2 diabetes.

Methods  This is a cross-sectional study. Nine hundred and one subjects were enrolled, including 501 patients with Type 2 diabetes, of whom 284 had at least one complication and 217 were without complications, and 400 control subjects. Leukocyte telomere length was measured by quantitative real-time PCR.

Results  Patients with diabetes complications had significantly shorter leukocyte telomere length than both patients without diabetes complications and healthy control subjects. Moreover, among patients with diabetes complications, leukocyte telomere length became significantly and gradually shorter with the increasing number of diabetes complications. The magnitude of the effect of the decrease of the abundance of telomeric template vs. a single-copy gene length (T/S ratio) on complications is described by the estimated odds ratio OR = 5.44 (95% CI 3.52-8.42).

Conclusions  The results of the study support the hypothesis that telomere attrition may be a marker associated with the presence and the number of diabetic complications.

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