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bolic syndrome in the general population, this indicator was considered as a candidate for DRI development.

Biological Plausibility

Vitamin D was first implicated as a modulator of pancreatic endocrine function and insulin synthesis and secretion in studies using rodent models more than three decades ago (Norman et al., 1980; Clark et al., 1981; Chertow et al., 1983). Since then, the role of calcitriol in the synthesis and secretion of insulin and regulation of calcium trafficking in β-islet cells as well as its effects on insulin action have been established in both rodent models and in vitro cell culture models (Frankel et al., 1985; Cade and Norman, 1986; Faure et al., 1991; Sergeev and Rhoten, 1995; Billaudel et al., 1998; Bourlon et al., 1999). These findings stimulated observational and intervention studies examining the role of vitamin D and calcium in type 2 diabetes and metabolic syndrome in humans.

Systematic Reviews and Meta-Analyses

Neither AHRQ-Ottawa nor AHRQ-Tufts included type 2 diabetes or metabolic syndrome in its systematic review, although AHRQ-Tufts did include body weight as a health outcome and found no effect of vitamin D or calcium on changes in body weight. A systematic review and meta-analysis by Pittas et al. (2007b) included a large body of observational evidence and six intervention studies (four small short-term and two long-term studies) of vitamin D supplementation, one study using combined vitamin D and calcium supplementation and five studies using calcium alone or dairy supplementation. The results from these trials were largely negative; among the short-duration vitamin D trials, three studies reported no effect, and one reported enhanced insulin secretion but no improvement in glucose tolerance following vitamin D supplementation. In one study included in the review, however, the relationship was statistically significant only when non-Hispanic blacks were excluded from the meta-analysis.

Overall, the evidence reviewed from the intervention studies did not support a role for vitamin D alone, although vitamin D in combination with calcium supplementation may have a role in preventing type 2 diabetes in populations already at risk. The observational evidence in the review included cross–sectional and case–control studies in which serum vitamin D and calcium levels were determined from individuals in a population with established glucose intolerance. Similar confounding and a lack of adjustment for confounders limited the cohort studies. Thus, the one meta-analysis that included both observational and intervention studies could

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