Chen Hui, Karne Rajaram J, Hall Gail, Campia Umberto, Panza Julio A, Cannon Richard O, Wang Yaohui, Katz Arie, Levine Mark, Quon Michael J
Diabetes Unit, National Center for Complementary and Alternative Medicine, NIH, Bldg. 10, Rm. 6C-205, 10 Center Dr. MSC 1632, Bethesda, MD 20892-1632, USA.
Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H137-45. doi: 10.1152/ajpheart.00768.2005. Epub 2005 Aug 26.
Endothelial dysfunction is a hallmark of Type 2 diabetes related to hyperglycemia and oxidative stress. Nitric oxide-dependent vasodilator actions of insulin may augment glucose disposal. Thus endothelial dysfunction may worsen insulin resistance. Intra-arterial administration of vitamin C improves endothelial dysfunction in diabetes. In the present study, we investigated effects of high-dose oral vitamin C to alter endothelial dysfunction and insulin resistance in Type 2 diabetes. Plasma vitamin C levels in 109 diabetic subjects were lower than healthy (36 +/- 2 microM) levels. Thirty-two diabetic subjects with low plasma vitamin C (<40 microM) were subsequently enrolled in a randomized, double-blind, placebo-controlled study of vitamin C (800 mg/day for 4 wk). Insulin sensitivity (determined by glucose clamp) and forearm blood flow in response to ACh, sodium nitroprusside (SNP), or insulin (determined by plethysmography) were assessed before and after 4 wk of treatment. In the placebo group (n = 17 subjects), plasma vitamin C (22 +/- 3 microM), fasting glucose (159 +/- 12 mg/dl), insulin (19 +/- 7 microU/ml), and SI(Clamp) [2.06 +/- 0.29 x 10(-4) dl x kg(-1) x min(-1)/(microU/ml)] did not change significantly after placebo treatment. In the vitamin C group (n = 15 subjects), basal plasma vitamin C (23 +/- 2 microM) increased to 48 +/- 6 microM (P < 0.01) after treatment, but this was significantly less than that expected for healthy subjects (>80 microM). No significant changes in fasting glucose (156 +/- 11 mg/dl), insulin (14 +/- 2 microU/ml), SI(Clamp) [2.71 +/- 0.46 x 10(-4) dl x kg(-1) x min(-1)/(microU/ml)], or forearm blood flow in response to ACh, SNP, or insulin were observed after vitamin C treatment. We conclude that high-dose oral vitamin C therapy, resulting in incomplete replenishment of vitamin C levels, is ineffective at improving endothelial dysfunction and insulin resistance in Type 2 diabetes.
内皮功能障碍是2型糖尿病的一个标志，与高血糖和氧化应激有关。胰岛素依赖一氧化氮的血管舒张作用可能会增强葡萄糖的处置。因此，内皮功能障碍可能会加重胰岛素抵抗。动脉内给予维生素C可改善糖尿病患者的内皮功能障碍。在本研究中，我们调查了高剂量口服维生素C对改变2型糖尿病患者内皮功能障碍和胰岛素抵抗的影响。109名糖尿病患者的血浆维生素C水平低于健康人（36±2微摩尔）水平。随后，32名血浆维生素C水平低（<40微摩尔）的糖尿病患者被纳入一项维生素C的随机、双盲、安慰剂对照研究（800毫克/天，共4周）。在治疗4周前后，评估胰岛素敏感性（通过葡萄糖钳夹法测定）以及对乙酰胆碱、硝普钠（SNP）或胰岛素的前臂血流情况（通过体积描记法测定）。在安慰剂组（n = 17名受试者）中，安慰剂治疗后血浆维生素C（22±3微摩尔）、空腹血糖（159±I2毫克/分升）、胰岛素（19±7微单位/毫升）和SI(Clamp) [2.06±0.29×10(-4)分升×千克(-1)×分钟(-1)/(微单位/毫升)]均无显著变化。在维生素C组（n = 15名受试者）中，治疗后基础血浆维生素C（23±2微摩尔）升至48±6微摩尔（P<0.01），但这显著低于健康受试者预期水平（>80微摩尔）。维生素C治疗后，空腹血糖（156±11毫克/分升）、胰岛素（14±2微单位/毫升）、SI(Clamp) [2.71±0.46×10(-4)分升×千克(-1)×分钟(-1)/(微单位/毫升)]或对乙酰胆碱、SNP或胰岛素的前臂血流均未观察到显著变化。我们得出结论，高剂量口服维生素C疗法虽能使维生素C水平得到部分补充，但对改善2型糖尿病患者的内皮功能障碍和胰岛素抵抗无效。
