Ceriello Antonio, Novials Anna, Ortega Emilio, Canivell Silvia, Pujadas Gemma, La Sala Lucia, Bucciarelli Loredana, Rondinelli Maurizio, Genovese Stefano
Cardiovasc Diabetol. 2013 Jun 27;12:97. doi: 10.1186/1475-2840-12-97.
It has been reported that hyperglycemia following hypoglycemia produces an ischemia-reperfusion-like effect in type 1 diabetes. In this study the possibility that GLP-1 has a protective effect on this phenomenon has been tested.
15 type 1 diabetic patients underwent to five experiments: a period of two hours of hypoglycemia followed by two hours of normo-glycemia or hyperglycemia with the concomitant infusion of GLP-1 or vitamin C or both. At baseline, after 2 and 4 hours, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2alpha, sCAM-1a, IL-6 and flow mediated vasodilation were measured.
After 2 h of hypoglycemia, flow mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine and IL-6 significantly increased. While recovering with normoglycemia was accompanied by a significant improvement of endothelial dysfunction, oxidative stress and inflammation, a period of hyperglycemia after hypoglycemia worsens all these parameters. These effects were counterbalanced by GLP-1 and better by vitamin C, while the simultaneous infusion of both almost completely abolished the effect of hyperglycemia post hypoglycemia.
This study shows that GLP-1 infusion, during induced hyperglycemia post hypoglycemia, reduces the generation of oxidative stress and inflammation, improving the endothelial dysfunction, in type 1 diabetes. Furthermore, the data support that vitamin C and GLP-1 may have an additive protective effect in such condition.
据报道,低血糖后的高血糖在1型糖尿病中会产生类似缺血再灌注的效应。在本研究中,已对胰高血糖素样肽-1(GLP-1)对此现象具有保护作用的可能性进行了测试。
15名1型糖尿病患者接受了五项实验:一段两小时的低血糖期,随后是两小时的血糖正常或高血糖期,同时输注GLP-1或维生素C或两者。在基线时、2小时和4小时后,测量血糖、血浆硝基酪氨酸、血浆8-异前列腺素F2α、可溶性细胞间黏附分子-1a(sCAM-1a)、白细胞介素-6(IL-6)和血流介导的血管舒张。
低血糖2小时后,血流介导的血管舒张显著降低,而可溶性细胞间黏附分子-1(sICAM-1)、8-异前列腺素F2α、硝基酪氨酸和IL-6显著增加。血糖正常恢复时伴随着内皮功能障碍、氧化应激和炎症的显著改善,低血糖后的高血糖期则使所有这些参数恶化。这些效应被GLP-1抵消,维生素C的作用更好,而同时输注两者几乎完全消除了低血糖后高血糖的效应。
本研究表明,在1型糖尿病患者低血糖后诱导的高血糖期间输注GLP-1可减少氧化应激和炎症的产生,改善内皮功能障碍。此外,数据支持维生素C和GLP-1在这种情况下可能具有相加的保护作用。