Vitamin D, Inflammation, and Relations to Insulin Resistance in Morbidly Obese Pre-Menopausal Women
thesisposted on 28.06.2013 by Van T. Nguyen
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Vitamin D has traditionally been known to involve in calcium homeostasis and prevent rickets; recently it has been recognized to inversely associate with many non-skeletal diseases and conditions including obesity and type 2 diabetes. In vitro studies demonstrated that vitamin D possesses anti-inflammatory properties. It remains unknown if the effect of vitamin D on insulin sensitivity is mediated by suppressing inflammation in human adipose tissues. Obese women (n=76) approved for bariatric surgeries at UIC medical center were recruited. 2-hour oral glucose tolerance test was performed; insulin sensitivity was assessed. mRNA expression of vitamin D receptor (VDR), CD68, collagen VI and various inflammatory genes in visceral (VAT) and subcutaneous adipose tissues (SAT) were assessed. 82% of the subjects were normal glucose tolerance. Nearly 90% of our subjects were vitamin D adequate. There was no association between 25OHD and insulin sensitivity, CRP and IL6. When analysis was restricted to subjects with elevated CRP (>=5.2 µg/ml) a significant negative association between 25OHD and CRP (r=-0.33, p=0.04) was found. There was no association between serum 25OHD and adipose tissue VDR mRNA expression. 25OHD negatively correlated with TNFα mRNA expression in VAT (r= -0.83, p=0.04) only in subjects who were vitamin D inadequate. There were significant positive correlations between logVDR mRNA expression and log of mRNA expression of collagen VI (p<0.0001), log IL1β (p<0.0001), log TNFα (p<0.0001) in both adipose depots. LogVDR mRNA expression significantly and positively predicted logHOMA-IR among non-African American (β=1.67, p=0.05, R2=0.16). In conclusion, we found that there are women displaying remarkably healthy metabolic profiles and sufficient vitamin D levels despite their morbid obesity. Our study supports the concept of threshold optimal 25OHD levels above which negligible effect on metabolic outcome is observed. Whether there are different optimal levels for different health outcomes remains to be explored. We found that VDR does not relate to circulating levels of vitamin D in vitamin D sufficient individuals and does not possess protective effect in adipose tissues as in other tissues. Further investigations in individuals with a broader spectrum of vitamin D levels are warranted.