Vitamins D, C, and E in Preventing Type 2 Diabetes

This review examines current knowledge linking oxidation, inflammatory signaling pathways, and vitamin supplementation or intake to the risk of T2DM….

The concept that micronutrients, via attenuation of inflammation, could be employed as a novel preventive measure for T2DM is evaluated in the context of its relevance to public health. 

The incidence of Type 2 diabetes is increasing worldwide, and certain population subgroups are especially vulnerable to the disease. To reduce T2DM risk and progression at the population level, preventative strategies are needed that can be implemented on a population-wide scale with minimal cost and effort. Chronic low-grade inflammation resulting from oxidative stress and imbalances in the innate immune system has been associated with obesity, metabolic syndrome, and insulin resistance – critical stages in the development and progression of T2DM. Therefore, inflammation may play a causal role in the pathogenesis of T2DM, and reducing it via modulation of oxidative stress and the innate immune response could lead to a status of improved insulin sensitivity and delayed disease onset. Dietary supplementation with anti-inflammatory and antioxidant nutritional factors, such as micronutrients, might present a novel strategy toward the prevention and control of T2DM at the population level.  

Introducing novel and effective prevention strategies in a public health setting necessitates considering approaches with the least (if any) side effects and the maximal preventive efficacy and outcome. In this context, applying nutritional intervention to attenuate inflammation and oxidative stress would be a feasible public health strategy for prevention of T2DM. 

This approach should be explored in prediabetic subjects and the outcome should be compared to the effect(s) of modifying current practices, such as lifestyle change, dietary intervention, and exercise. The effectiveness of lifestyle-change intervention programs for prediabetes also shows a promising effect on the reduction of overall incidence of T2DM or its complications, and it can be implemented in general clinical practice. 

A lifestyle-change program including increased exercise and change in diet (either by reduction in glycemic load or reduced-fat diet) demonstrated a significant difference between control and intervention groups in markers for risk of progression to T2DM including weight, BMI, and waist circumference. 

In general, current approaches for the prevention of T2DM have been shown to be effective in delaying or preventing the progression from prediabetes to diabetes. In patients with insulin resistance, these practices are known to improve insulin sensitivity and the overall predisposition to T2DM. On the other hand, increasing intake of vitamin D to .800 IU daily along with 1200 mg of calcium was reported to reduce the risk of developing T2DM by 33%. 

In agreement, healthy older adults with impaired fasting glucose showed significant improvement in attenuating the glycemic response and insulin resistance when they increased their intake of vitamin D by 700 IU/day and calcium by 500 mg/day for 3 years. 

It seems reasonable, therefore, to suggest that the two preventive approaches for T2DM, that is micronutrient supplementation and lifestyle change, may be combined into a single successful intervention program. This strategy may be more efficient in reducing the burden of the disease in the general population and in vulnerable subpopulations than when a single approach is proposed. Moreover, such a combined approach may be introduced into the general practice setting and to the general population with low expenditure and minimal side effects. 

Overall, the current state of knowledge warrants further study into the extent to which micronutrients can modify the association between markers of inflammation and oxidative stress and early stages of T2DM. There is evidence supporting the idea that vitamin supplementation can modify the genotype–phenotype association within the innate immune response (i.e., the proinflammatory and inflammatory markers) and that it has an ameliorating effect on oxidative stress and the subsequent proinflammatory signaling. This proposition may provide the mechanism by which nutritional factors prevent or delay disease development and can be introduced into the general population, as well as susceptible subpopulations. 

In relation to the current preventive approaches for T2DM, for example, lifestyle changes, exercise, and dietary intervention, exploring the efficacy of micronutrient supplementation on attenuating oxidative stress, the innate immune response, and the ensuing inflammation and evaluating the outcome of this strategy on T2DM incidence may be assessed through a series of prospective population-based studies, first, to determine the feasibility and effectiveness of this protocol; second, to validate and evaluate this strategy and ensure replication of results; and, third, to monitor the outcome to quantify the overall preventive response in comparison with the current approaches.

As reviewed by Willcox et al, study design is an issue to consider when assessing the efficacy of antioxidants in reducing the risk of developing cardiometabolic diseases. Intervention trials should be designed with sufficient power to measure T2DM as a primary, rather than a secondary, outcome. Furthermore, these studies should investigate the effects of antioxidant vitamins and trace elements in representative populations so that the results are applicable to high-risk groups, and they should take into account genetic variation accounting for interindividual differences in response to supplementation. Consideration should be also given to the antioxidants given in specific studies, as different antioxidants exert their effects through different mechanisms.

Biologics: Targets & Therapy, Jan 18, 2011 Bibiana Garcia-Bailo, Ahmed El-Sohemy