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most did not find a significant positive association between vitamin D and calcium intake and risk for CVD. Taken together, this observational evidence was strong enough to support a relationship between serum 25OHD levels and incident disease, but not a conclusion that higher serum 25OHD levels were associated with a lower risk for CVD. Additionally, the review of randomized trial evidence does not support a causal relationship between vitamin D intake and risk for CVD.

Concluding Statement

Review of the available evidence, from both RCTs and observational studies on associations between vitamin D and calcium intake and risk for CVD shows that although observational evidence supports a relationship between serum 25OHD levels and the presence of CVD, it does not show a relationship with risk for developing CVD, and evidence was not found for a causal relationship between vitamin D intake and development of disease. Given the lack of statistically significant evidence supporting associations between vitamin D intake or serum 25OHD level and risk for CVD and the lack of evidence on CVD as a primary outcome of treatment in RCTs with vitamin D and/or calcium, the committee could not draw an inference about the efficacy of this indicator to support DRI development.

Diabetes and Metabolic Syndrome

Type 2 diabetes is a blood glucose disorder characterized by insulin resistance and relative insulin deficiency. Metabolic changes that accompany chronic elevated blood glucose levels frequently lead to functional impairment in many organ systems, particularly the cardiovascular system, which contributes to substantially increased risk of morbidity and mortality.

Metabolic syndrome is a condition characterized by a constellation of metabolic risk factors, including abdominal obesity, atherogenic dyslipidemias, elevated blood pressure, insulin resistance, prothrombotic state, and proinflammatory state (e.g., elevated C-reactive protein).

Individuals with metabolic syndrome are at increased risk of coronary heart disease, stroke, peripheral vascular disease, and type 2 diabetes. Adiposity is a component of both type 2 diabetes and metabolic syndrome, which may have an impact on vitamin D status. Since the release of the 1997 DRIs (IOM, 1997), a number of studies have been published on relationships between vitamin D with or without calcium and type 2 diabetes and metabolic syndrome. The committee recognized that obesity can be a confounder to vitamin D analysis. However, as it is a component of the health outcome and because of the prevalence of both obesity and meta-

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