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Vitamin C further improves the protective effect of glucagon-like peptide-1 on acute hypoglycemia-induced oxidative stress, inflammation, and endothelial dysfunction in type 1 diabetes.
Ceriello, A, Novials, A, Ortega, E, Canivell, S, La Sala, L, Pujadas, G, Bucciarelli, L, Rondinelli, M, Genovese, S
Diabetes care. 2013;(12):4104-8
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Abstract
OBJECTIVE To test the hypothesis that acute hypoglycemia induces endothelial dysfunction and inflammation through the generation of an oxidative stress. Moreover, to test if the antioxidant vitamin C can further improve the protective effects of glucagon-like peptide 1 (GLP-1) on endothelial dysfunction and inflammation during hypoglycemia in type 1 diabetes. RESEARCH DESIGN AND METHODS A total of 20 type 1 diabetic patients underwent four experiments: a period of 2 h of acute hypoglycemia with or without infusion of GLP-1 or vitamin C or both. At baseline, after 1 and 2 h, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2a (PGF2a), soluble intracellular adhesion molecule-1a (sICAM-1a), interleukin-6 (IL-6), and flow-mediated vasodilation were measured. At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced. RESULTS At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced. CONCLUSIONS This study shows that vitamin C infusion, during induced acute hypoglycemia, reduces the generation of oxidative stress and inflammation, improving endothelial dysfunction, in type 1 diabetes. Furthermore, the data support a protective effect of GLP-1 during acute hypoglycemia, but also suggest the presence of an endothelial resistance to the action of GLP-1, reasonably mediated by oxidative stress.
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Evidence that hyperglycemia after recovery from hypoglycemia worsens endothelial function and increases oxidative stress and inflammation in healthy control subjects and subjects with type 1 diabetes.
Ceriello, A, Novials, A, Ortega, E, La Sala, L, Pujadas, G, Testa, R, Bonfigli, AR, Esposito, K, Giugliano, D
Diabetes. 2012;(11):2993-7
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Abstract
Currently there is debate on whether hypoglycemia is an independent risk factor for atherosclerosis, but little attention has been paid to the effects of recovery from hypoglycemia. In normal control individuals and in people with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normoglycemia or hyperglycemia for another 2 h and then maintaining normal glycemia for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. Recovery with normoglycemia is accompanied by a significant improvement in endothelial dysfunction, oxidative stress, and inflammation, which are affected by hypoglycemia; however, a period of hyperglycemia after hypoglycemia worsens all of these parameters, an effect that persists even after the additional 6 h of normoglycemia. This effect is partially counterbalanced when hyperglycemia after hypoglycemia is accompanied by the simultaneous infusion of vitamin C, suggesting that when hyperglycemia follows hypoglycemia, an ischemia-reperfusion-like effect is produced. This study shows that the way in which recovery from hypoglycemia takes place in people with type 1 diabetes could play an important role in favoring the appearance of endothelial dysfunction, oxidative stress, and inflammation, widely recognized cardiovascular risk factors.
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Pramlintide reduced markers of oxidative stress in the postprandial period in patients with type 2 diabetes.
Ceriello, A, Lush, CW, Darsow, T, Piconi, L, Corgnali, M, Nanayakkara, N, Frias, JP, Maggs, D
Diabetes/metabolism research and reviews. 2008;(2):103-8
Abstract
BACKGROUND The production of oxidative stress as a result of postprandial hyperglycaemia is now recognized as an important contributing factor in the development of diabetes complications. The objective of this study was to examine the effects of pramlintide on plasma concentrations of glucose and several markers of oxidative stress in patients with type 2 diabetes following a standardized meal. METHODS This was a randomized, single-blind, placebo-controlled, crossover study conducted at two clinical research centres in the United States. A total of 19 subjects (9 men and 10 women) with type 2 diabetes using mealtime insulin participated in the study. Pramlintide (120 microg), or placebo, and rapid-acting mealtime insulin were administered prior to a standardized meal on two separate study days. Plasma concentrations of glucose, nitrotyrosine (NT), oxidized-LDL cholesterol (OxLDL-C), and total radical trapping parameter (TRAP) were assessed during the 4-h postprandial period. RESULTS Compared to placebo, pramlintide treatment reduced postprandial excursions of glucose, NT, and OxLDL-C and protected TRAP from consumption. Correlation analysis revealed positive associations between placebo-corrected glucose incremental AUC(0-4 h) and both NT and OxLDL-C and a negative association between placebo-corrected glucose incremental AUC(0-4h) and TRAP. CONCLUSIONS The reduction in postprandial glucose excursions achieved with addition of pramlintide to rapid-acting insulin in type 2 diabetes was associated with a reduction in postprandial markers of oxidative stress.
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High-glycemic index carbohydrate increases nuclear factor-kappaB activation in mononuclear cells of young, lean healthy subjects.
Dickinson, S, Hancock, DP, Petocz, P, Ceriello, A, Brand-Miller, J
The American journal of clinical nutrition. 2008;(5):1188-93
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BACKGROUND High-glycemic index diets have been linked to greater risk of cardiovascular disease and type 2 diabetes. Postprandial glycemia within the normal range may promote oxidative stress and inflammatory processes underlying the development of disease. OBJECTIVE We explored acute differences in the activation of the inflammatory marker nuclear factor-kappaB after consumption of 2 carbohydrate meals matched for macronutrient and micronutrient composition but differing in glycemic index. DESIGN After an overnight fast, 10 young, lean healthy subjects were fed in random order 3 meals providing 50 g of available carbohydrate as glucose, white bread, or pasta. Venous blood samples were collected at 0, 1, 2, and 3 h, and nuclear proteins were extracted from mononuclear cells. Changes in nuclear factor-kappaB-p65 proteins were detected by Western blotting. Acute changes in other markers of oxidative stress (nitrotyrosine and soluble intercellular adhesion molecule-1) were also assessed. RESULTS The maximum increase in nuclear factor-kappaB activation was similar after the bread meal [mean (+/-SEM) area under the curve: 69 +/- 16% optical density x h] and the glucose challenge (75 +/- 9% optical density x h), but was 3 times higher than after the pasta meal (23 +/- 5% optical density x h) (P < 0.05). Similarly, changes in nitrotyrosine, but not soluble intercellular adhesion molecule-1, were higher after glucose and bread than after pasta (P = 0.01 at 2 h). CONCLUSIONS The findings suggest that high-normal physiologic increases in blood glucose after meals aggravate inflammatory processes in lean, young adults. This mechanism may help to explain relations between carbohydrates, glycemic index, and the risk of chronic disease.
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Effects of macronutrient excess and composition on oxidative stress: relevance to diabetes and cardiovascular disease.
Ceriello, A
Current atherosclerosis reports. 2006;(6):472-6
Abstract
Type 2 diabetes is a disease that is increasing in prevalence worldwide. In genetically predisposed patients, the combination of excess caloric intake and reduced physical activity induces a state of insulin resistance. When beta-cells are not able to compensate for insulin resistance by adequately increasing insulin production, impaired glucose tolerance occurs, which is characterized by excessive postprandial hyperglycemia. Impaired glucose tolerance may evolve into overt diabetes. These three conditions (ie, insulin resistance, impaired glucose tolerance, and overt diabetes) are associated with an increased risk of cardiovascular disease. Intervention trials have demonstrated that diabetes can be prevented by means of lifestyle modifications, antidiabetic drugs directed against insulin resistance or simply postprandial hyperglycemia, and cardiovascular drugs devoid of effects on blood glucose levels. All of these have intracellular antioxidant effects. Evidence on the efficacy of antioxidant interventions is accumulating, and oxidative stress may be a therapeutic target to prevent diabetes as well as cardiovascular complications.
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Red wine protects diabetic patients from meal-induced oxidative stress and thrombosis activation: a pleasant approach to the prevention of cardiovascular disease in diabetes.
Ceriello, A, Bortolotti, N, Motz, E, Lizzio, S, Catone, B, Assaloni, R, Tonutti, L, Taboga, C
European journal of clinical investigation. 2001;(4):322-8
Abstract
BACKGROUND Oxidative stress and thrombosis have been reported to be increased in diabetic patients and involved in the pathogenesis of cardiovascular complications. It has been demonstrated in diabetic patients that consumption of a meal is accompanied by the generation of an oxidative stress and of a hypercoagulable state. It is well recognized that red wine shows antithrombotic activity and that its ingestion increases plasma antioxidant capacity in man. In this study the possibility that red wine consumption may reduce the oxidative stress and thrombosis produced postprandially in diabetic patients has been evaluated. SUBJECTS AND METHODS Twenty type 2 diabetic patients were studied during fasting consumption of 300 mL of red wine, or during a meal accompanied, or not, by red wine ingestion. RESULTS Plasma glucose, insulin, triglycerides, total plasma radical-trapping capacity, activated factor VII and prothrombin fragments 1 + 2 were measured in basal state and at 60, 120 and 180 min after the start of each experiment. Low-density lipoprotein (LDL) oxidation was also evaluated at baseline and after 120 min Plasma glucose, insulin, triglycerides and LDL oxidation significantly increased, while the total plasma radical-trapping parameter significantly decreased during the meal test. Consumption of red wine in the fasting state significantly increased total plasma radical-trapping parameter activity, while wine ingestion with a meal counterbalanced the decrease of total plasma radical-trapping parameter and the increase of LDL oxidation. Meal consumption induced an increase in plasma prothrombin fragments 1 + 2 and activated factor VII in diabetic patients. Wine ingestion with the meal significantly reduced the production of both prothrombin fragments 1 + 2 and activated factor VII. Fasting consumption of red wine alone did not show effects on coagulation or LDL oxidation. CONCLUSION This finding confirms that in the absorptive phase free radicals are produced in diabetic patients, which reduce serum antioxidant defences, increase LDL oxidation and activate the coagulation system. Red wine consumption during a meal significantly preserves plasma antioxidant defences and reduces both LDL oxidation and thrombotic activation. The consumption of a moderate amount of red wine during meals may have a beneficial effect in the prevention of cardiovascular disease in diabetic patients.