## 5 Potential Roles for Vitamin D as a Therapeutic Option in Inflammasome Disorders
### Metabolic Disease  
Observational evidence supports an association between low VD levels and metabolic conditions such as type 2 diabetes mellitus (T2 DM) [65], atherosclerotic disease [66; 67], and obesity [44; 68].  
\begin{table}
\begin{tabular}{l|c c c c c c} \hline \hline
**Region** & **VDD** & **AD** & **PD** & **MS** & **Obesity** & **T2 DM** \\ \hline
**South Africa** & 7-20\% & 0.26\% & 0.03\% & 0.01\% & 28.30\% & 4.50\% \\ \hline
**South America** & 20-59\% & 0.47\% & 0.09\% & 0.02\% & 23.79\% & 5.79\% \\ \hline
**Australia** & 31\% & 1.88\% & 0.17\% & 0.09\% & 29.00\% & 5.70\% \\ \hline
**USA** & 36\% & 1.24\% & 0.22\% & 0.16\% & 5.42\% & 10.31\% \\ \hline
**Mexico** & 38\% & 0.52\% & 0.05\% & 0.01\% & 28.90\% & 10.88\% \\ \hline
**Russian Federation** & 43-64\% & 0.71\% & 0.17\% & 0.07\% & 23.10\% & 7.60\% \\ \hline
**New Zealand** & 56\% & 0.86\% & 0.18\% & 0.15\% & 31.88\% & 5.20\% \\ \hline
**Europe** & 56\% & 0.16\% & 0.19\% & 0.19\% & 23.22\% & 16.61\% \\ \hline
**North Africa** & 60\% & 0.44\% & 0.55\% & 0.03\% & 25.77\% & 8.93\% \\ \hline
**Canada** & 60\% & 0.88\% & 0.29\% & 0.22\% & 29.40\% & 9.20\% \\ \hline
**Brazil** & 27\% & 0.82\% & 0.06\% & 0.01\% & 22.10\% & 6.40\% \\ \hline
**Asia** & 78-98\% & 0.99\% & 0.11\% & 0.01\% & 6.02\% & 4.42\% \\ \hline
**Middle East** & 30\% & 0.48\% & 0.05\% & 0.04\% & 26.81\% & 9.35\% \\ \hline
**Northern Europe** & 92\% & 1.27\% & 0.19\% & 0.16\% & 21.83\% & 5.52\% \\ \hline \hline \end{tabular}
\end{table}
Table 1: Global prevalence of vitamin D deficiency and other disorders.  
Several large, well-conducted trials have been conducted examining a role for VD supplementation in T2 DM. A large trial included 2423 patients who met the criteria for pre-diabetes but were not vitamin D-deficient. Patients received either 4000 IU/day of VD\({}_{3}\) or a placebo, and while there was a trend towards reduced risk of developing overt T2 DM, this did not reach statistical significance [69]. Similarly, in another large trial of 1312 diabetic patients not selected for VDD, supplementation of 2000 IU/day of VD\({}_{3}\) versus a placebo did not attenuate the diabetes-associated decline in renal function over 5 years of therapy [70]. However, two meta-analyses have suggested the benefit of VD supplementation on measures of glycaemic control and insulin resistance, albeit with some substantial heterogeneity between studies [71; 72].  
There are just a few small and heterogeneous studies of VD\({}_{3}\) or other VD analogue supplementation in patients with atherosclerosis, with mixed results ranging from no benefit all the way to significant attenuation of progressive atherosclerotic disease [73; 74; 75].  
Similarly, only two small pilot studies examining VD supplementation in obesity have been conducted. A pilot study of 18 overweight patients examined the effect of combined low-calorie diet and 25,000 IU/week VD\({}_{3}\) versus dieting alone. While there were no differences in weight loss, measures of insulin sensitivity did improve in those treated with VD\({}_{3}\)[76]. Meanwhile, a placebo-controlled trial of high-dose 100,000 IU bolus of VD\({}_{3}\) followed by 4000 IU/day over 4 months in 65 overweight patients showed no difference in functional outcomes, except in the subgroup of 20 patients with VDD who had a significant and clinically relevant improvement in back pain [77].