Vitamin D and Adipose Tissue Inflammation
Condition: Vitamin D Deficiency; Obesity; Type 2 Diabetes Mellitus; Intestinal Permeability
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Vitamin D Deficiency; Inflammation
Study type: Interventional

Summary: 
      Chronic, low-grade adipose tissue inflammation is a major risk factor for type 2 diabetes
      mellitus. The cause of adipose tissue inflammation has remained largely unclear. We
      hypothesize that vitamin D deficiency predisposes individuals to the development of adipose
      tissue inflammation, and that treatment of vitamin D deficient subjects with high dose
      vitamin D will reduce adipose tissue inflammation.
    

Detailed description: 
      The objective of this project is to investigate whether vitamin D modulates chronic low-grade
      adipose tissue inflammation in overweight and obese, vitamin D deficient men and women.

      Obesity is associated with insulin resistance and an increased risk for type 2 diabetes
      mellitus. Numerous studies, mostly conducted in mouse models of obesity, strongly suggest
      that chronic low-grade inflammation of adipose and other tissues is the major mechanism by
      which increased adiposity is linked to insulin resistance. Adipose tissue inflammation may
      therefore be a promising therapeutic target to reduce insulin resistance and the risk of type
      2 diabetes mellitus in obese individuals.

      Based on several lines of evidence, we hypothesize that vitamin D is an environmental factor
      that affects the course of the inflammatory response in most tissues of the body, including
      adipose tissue. In our previous studies, we found that circulating plasma concentrations of
      25-hydroxy vitamin D (25-OH-D) and the primary degradation product 24,25-dihydroxy vitamin D
      (24,25-OH2-D) were significantly associated with adipose tissue expression of adiponectin and
      negatively with TNF-alpha, even when adjusted for body mass index. Because these previous
      studies were cross-sectional, it is critical to complete an intervention study in humans to
      determine whether the observed association of vitamin D levels and adipose tissue
      inflammation is causal. The objectives of this pilot study are therefore to collect relevant
      preliminary data, and to begin an exploration of the mechanisms underlying this association
      such as intestinal permeability.

      Increased intestinal permeability may contribute to chronic low-grade inflammation and
      signaling through the vitamin D receptor plays an important role in the maintenance of
      intestinal integrity. We will assess whether normalization of vitamin D status is associated
      with changes in intestinal permeability.
    

Intervention name(s): Vitamin D3
Intervention type(s): Dietary Supplement
Intervention description(s): 2,000 or 4,000 IU/day vitamin D3 for 3 or 6 months.
Other intervention name(s): Carlson Labs Vitamin D3 capsules (2,000/4,000 IU/capsule)
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Vitamin D deficiency; Obesity; Inflammation; Low-grade, chronic inflammation; Adipose tissue inflammation; Diabetes; Type 2 diabetes mellitus; Insulin resistance; Intestinal permeability