Meta-Analysis: Antioxidants Lower HbA1c In Type 2 Diabetes

Role of Oxidative Stress in Type 2 Diabetes

For almost 25 years, oxidative stress has been considered to play a central part in the type 2 disease process, with over 6,000 related articles published over that time.

Some articles reflect growing evidence that cellular oxidative stress triggers cascades (p38 MAPK) that, in turn, interfere with signaling from the insulin receptor. Other findings suggest that diabetic complications arise from oxidative stress, which is defined as an imbalance of oxidants and antioxidants in the favor of oxidants. Hyperglycemia underlies the development of diabetic complications, most likely due to a greater production of free radicals, more specifically reactive oxygen and nitrogen species.

Combating Oxidative Stress

To combat oxidative stress, a number of trials have investigated administering vitamins C and/or E, since plasma levels of these nutrients are often reduced in those with type 2. In addition, epidemiological studies have found that type 2 individuals with reduced plasma status of vitamins C and E are at increased risk for cardiovascular events.

Antioxidant intervention trials in diabetic patients have not been uniform, however, and this has hindered their interpretation. Recently, researchers conducted a meta-analysis to clarify whether a defective antioxidant network contributes to insulin resistance in diabetes, or to its complications (1).

Study Design

Databases were searched for randomized, placebo-controlled trials examining the effect of supplemental vitamins E and/or C on glycemic control markers in non-pregnant adults with type 2 diabetes.

The analysis focused upon the effects of these nutrients on 1) plasma glucose and insulin concentrations as an indicator of the ability of the antioxidant to interfere with disease process, and 2) on glycated hemoglobin A1c (HbA1c) as a measure of antioxidant effects on protein modification implicated in disease complications.

Results

Fourteen vitamin E or C intervention studies were identified that met the study inclusion criteria. Collectively, these studies included 572 participants and ranged from 4 weeks to 12 months in duration.

Vitamin C supplementation was from 100 mg to 2 grams daily, while vitamin E supplementation ranged from 200 IU to 1800 IU per day.

Combined analysis revealed that antioxidant supplementation did not affect plasma glucose or insulin levels. However, HbA1c levels (reported in 13 of the 14 studies) were significantly reduced by the supplemental nutrients, suggesting that antioxidants have benefit in protecting against complications of the disease.

Key: Random effects model of meta- analysis of weighted mean difference of HbA1C compared to control group, showing the mean difference for each study and 95% confidence intervals, with the pooled meta-statistic shown as a diamond.

DL pooled effect size = -0.571078  (95% CI = -0.934883 to -0.207273)

Comments

HbA1c is the gold standard marker of long term glucose control, and a surrogate for risk of diabetic complications. This analysis found an overall improvement in HbA1c in patients receiving antioxidants (see figure), with the most pronounced effects seen in those getting higher dose vitamin E for at least 2 months.

While some concerns about high dose vitamin E safety have been previously reported, the most recent analysis (Cochrane review) does not support any negative or positive effects on mortality (2).

References

1. Akbar S et al. Dietary antioxidant interventions in type 2 diabetes patients: a meta-analysis. Br J of Diabetes Vasc Dis 11:62-68, 2011.
2. Bjelakovic G et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev (2):CD007176, 2008.