High-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance

被引:117
作者
Chen, H
Karne, RJ
Hall, G
Campia, U
Panza, JA
Cannon, RO
Wang, YH
Katz, A
Levine, M
Quon, MJ
机构
[1] NCCAM, Diabet Unit, NIH, Bethesda, MD 20892 USA
[2] NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA
[3] NIDDKD, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2006年 / 290卷 / 01期
关键词
hypertension; hyperglycemia; hypercholesterolemia; insulin sensitivity; sodium nitroprusside;
D O I
10.1152/ajpheart.00768.2005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 mu M) levels. Thirty-two diabetic subjects with low plasma vitamin C (< 40 mu M) 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 mu M), fasting glucose (159 +/- 12 mg/dl), insulin (19 +/- 7 mu U/ml), and SIClamp [2.06 +/- 0.29 X 10(-4) dl(.)kg(-1.)min(-1)/(mu U/ml)] did not change significantly after placebo treatment. In the vitamin C group (n = 15 subjects), basal plasma vitamin C (23 +/- 2 mu M) increased to 48 +/- 6 mu M ( P < 0.01) after treatment, but this was significantly less than that expected for healthy subjects (> 80 mu M). No significant changes in fasting glucose (156 +/- 11 mg/dl), insulin (14 +/- 2 mu U/ ml), SIClamp 2.71 +/- 0.46 X 10(-4) dl(.)kg(-1.)min(-1)/(mu U/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.
引用
收藏
页码:H137 / H145
页数:9
相关论文
共 83 条
[1]  
American Diabetes Association, 2004, Diabetes Care, V27 Suppl 1, pS5, DOI 10.2337/diacare.27.2007.S5
[2]   Effect of supplementary antioxidant vitamin intake on carotid arterial wall intima-media thickness in a controlled clinical trial of cholesterol lowering [J].
Azen, SP ;
Qian, DJ ;
Mack, WJ ;
Sevanian, A ;
Selzer, RH ;
Liu, CR ;
Liu, CH ;
Hodis, HN .
CIRCULATION, 1996, 94 (10) :2369-2372
[3]   INSULIN-MEDIATED SKELETAL-MUSCLE VASODILATION CONTRIBUTES TO BOTH INSULIN SENSITIVITY AND RESPONSIVENESS IN LEAN HUMANS [J].
BARON, AD ;
STEINBERG, HO ;
CHAKER, H ;
LEAMING, R ;
JOHNSON, A ;
BRECHTEL, G .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (02) :786-792
[4]   HEMODYNAMIC ACTIONS OF INSULIN [J].
BARON, AD .
AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 267 (02) :E187-E202
[5]   Effect of perfusion rate on the time course of insulin-mediated skeletal muscle glucose uptake [J].
Baron, AD ;
BrechtelHook, G ;
Johnson, A ;
Cronin, J ;
Leaming, R ;
Steinberg, HO .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1996, 271 (06) :E1067-E1072
[6]   Interaction between insulin sensitivity and muscle perfusion on glucose uptake in human skeletal muscle - Evidence for capillary recruitment [J].
Baron, AD ;
Tarshoby, M ;
Hook, G ;
Lazaridis, EN ;
Cronin, J ;
Johnson, A ;
Steinberg, HO .
DIABETES, 2000, 49 (05) :768-774
[7]   ROLE OF OXIDATIVE STRESS IN DEVELOPMENT OF COMPLICATIONS IN DIABETES [J].
BAYNES, JW .
DIABETES, 1991, 40 (04) :405-412
[8]   Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus [J].
Beckman, JA ;
Goldfine, AB ;
Gordon, MB ;
Garrett, LA ;
Keaney, JF ;
Creager, MA .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2003, 285 (06) :H2392-H2398
[9]   Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans [J].
Beckman, JA ;
Goldfine, AB ;
Gordon, MB ;
Creager, MA .
CIRCULATION, 2001, 103 (12) :1618-1623
[10]   INTERACTION BETWEEN GLUCOSE AND DEHYDROASCORBATE TRANSPORT IN HUMAN-NEUTROPHILS AND FIBROBLASTS [J].
BIGLEY, R ;
WIRTH, M ;
LAYMAN, D ;
RIDDLE, M ;
STANKOVA, L .
DIABETES, 1983, 32 (06) :545-548