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Diabetes  |  HIV  |  Hypertension

Antioxidants: Diabetes

Introduction

Several studies have found biomarkers of oxidative stress to be elevated in diabetic patients, particularly in patients with poor glycemic control.  The Diabetes Control and Complications Trial (DCCT) has shown that the complications of diabetes can be delayed and reduced by maintaining tight glycemic control. [1]  The role of oxidative stress associated with diabetes and its complications is an active area of research. 

Oxidative Stress in Diabetes

Blood analysis of lipid peroxides and measurement of urinary isoprostanes provide evidence that oxidative stress is enhanced in patients with diabetes. [2]  Hyperglycemia can increase the generation of free radicals via autoxidation events, polyol pathways, and Amadori reactions. [3-4] This enhanced oxidative stress can, in turn, induce vascular damage via several pathways, including the formation of advanced glycated end products that are proatherogenic and prothrombotic. [5]  The impact of these changes in the context of atherosclerosis progression is still unclear.  Evidence supporting a role for oxidative stress in contributing to the deterioration of vascular disease includes a demonstration that endothelium dependent vasodilation is reduced in patients with diabetes and that vitamin C is able to prevent it. [6]

Antioxidant Micronutrient Status

Studies measuring the circulating concentration of vitamins E and C in patients with risk factors for atherosclerosis have reported extreme variability in the data, particularly among smokers and diabetics.5  The range of plasma vitamin C values reported in NIDDM patients is 30.4 - 87.5 μmol/L, and 8.45 - 63.6 μmol/L in IDDM patients.  Plasma vitamin E values in both NIDDM and IDDM patients were reported in the range of 3.81 - 5.78 μmol/mmol cholesterol.

In one study of diabetic patients, blood levels of antioxidants were unrelated to dietary intakes; vitamins A and E were, however, found to be correlated with serum lipids. [7]  In another study dietary vitamin C intake was found to be the same in Type II diabetic patients and non-diabetic control subjects, yet serum levels of this vitamin were significantly lower in the diabetic patients, suggesting increased ascorbate utilization in diabetics. [8]

Antioxidant Supplementation

High dose vitamin E supplementation (1800 IU/d) for 4 months normalizes retinal hemodynamic abnormalities and improves renal function in Type I diabetics. [9]  In Type II diabetics, supplementation with a lower dose (200 IU/d) for the same duration had no effect on insulin, glycated hemoglobin, or fasting blood sugar. [10]  However, at 600 IU/d vitamin E a 7.3% reduction in insulin sensitivity was observed in obese Type 2 diabetic subjects. [11 ]These results suggest that some people may experience untoward results from an antioxidant intervention.

A combination of the antioxidant micronutrients including vitamin E, vitamin C, Mg, and Zn was able to lower blood pressure in Type II diabetics after 3 months. [12] Furthermore, high–dose supplementation with vitamins C and E for 1 month lowered the urinary albumin excretion rate in Type II diabetics with micro/macroalbuminuria. [13]

Interestingly, high-dose oral vitamin C supplementation (800 mg/d) for 1 month increased plasma vitamin C levels in Type II diabetics, but the change from baseline was significantly less than expected for healthy subjects. [14] Consequently this therapy was ineffective at improving endothelial dysfunction and insulin resistance in these patients.  These findings are in contrast with other studies that have found improved endothelial dysfunction in diabetics following intra-arterial administration of vitamin C.  

Critical Thinking Questions:

1. Are elevated levels of oxidative stress always associated with low antioxidant status?

1. Why is there such a large variability in antioxidant nutrient status data among diabetics?

1. Should supplementation be considered in subgroups of patients at high risk of complications?

1. What indicators of oxidative stress should be used in determining whether a diabetic patient is a good candidate for supplementation?

1. How might renal failure affect oxidative stress?

1. Might any of the drugs used in diabetics interfere with the body’s antioxidant defense network?

1. How might improving antioxidant status affect inflammation?

1. Why might some diabetics respond to antioxidant supplementation better than others?

1. Should dietary antioxidants be considered as a potential adjunct in the treatment of diabetes?

Links:

Professional Societies, Agencies, and Government Organizations:

American Diabetes Association:

Evidence-Based Nutrition Principles and Recommendations for the Treatment and Prevention of Diabetes and Related Complications
http://care.diabetesjournals.org/cgi/content/full/25/suppl_1/s50

Diabetes Research Summaries – Nutrition:
http://www.diabetes.org/diabetes-research/summaries/nutrition.jsp

Centers for Disease Control (CDC):

Diabetes Prevention Program:
http://www.cdc.gov/diabetes/news/docs/dpp.htm

Joslin Diabetes Center:

What are the best vitamins and minerals to take?:
http://www.joslin.org/managing_your_diabetes_701.asp