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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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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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Abstract
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.