Lara C. Pullen, PhD

June 27, 2014

CHICAGO — African American men at risk for diabetes and with low levels of vitamin D benefit from 50,000 units per week of supplementation with this vitamin, according to the results of a new study.

The D Vitamin Intervention in Veterans Administration (DIVA) trial was designed to determine whether vitamin-D supplementation improves early markers of diabetes in African American men at high risk for the disease or those newly diagnosed with type 2 diabetes mellitus. Investigators also collected data on gut microbiota and markers of leaky gut.

Vitamin-D supplementation not only improved insulin sensitivity but also shifted the microbiome from a prediabetes spectrum to a healthy signature. Serum markers of gut permeability were also improved in men treated with vitamin D. Taken together, the results suggest that vitamin D may modulate gut permeability and prevent low-grade inflammation associated with obesity and insulin resistance.

"You need a certain level of vitamin D to see anti-inflammatory effects. You need to go much higher [than many trials have done]," Irina Ciubotaru, MD, PhD, from the section of endocrinology, the University of Illinois, Chicago, told Medscape Medical News. She explained that in her study population, the participants were taken from an average baseline of 11.7 ng/mL of vitamin D to an average posttreatment level of 56 ng/mL.

Dr. Ciubotaru presented her research here at ICE/ENDO 2014.

"Studies like this are always fascinating....They do suggest future experiments where one might manipulate the microbiota," commented session chair, S. Mitch Harmon, MD, PhD, from the Phoenix VA Healthcare System in Arizona.

Can High Levels of Vitamin D Delay Development of Type 2 Diabetes?

Dr. Ciubotaru described the DIVA study, which examined the effect of 1 year of 50,000 vitamin-D treatment weekly in 116 veterans; although all subjects were prescribed vitamin D, not all were compliant. She therefore reported results only for those who had vitamin-D levels greater than 40 ng/mL after 1 year of supplementation.

When evaluating the microbiota, the researchers focused primarily on the most abundant taxa but also documented some of the less abundant that had no obvious metabolic role. Dr. Ciubotaru noted that the most significant differences in microbiota composition were measurable at the extreme quartiles of vitamin-D levels.

There was a negative association between vitamin-D level and gut Prevotella, suggesting an interaction between vitamin D and this genus of Gram-negative bacteria that is associated with a carbohydrate-based diet. Dr. Ciubotaru hypothesized that vitamin D may influence the microbiome via vitamin-D–receptor signaling or that the microbiome may influence the clearance of vitamin D.

They also found a positive association of caloric and macronutrient intake with Prevotella abundance. There was an inverse association of caloric intake with Akkermansia. Both of these results are consistent with previous studies.

Notably, "microbial diversity was a significant predictor of HbA1c," she observed. In addition, vitamin D appeared to play a role in delaying the development of type 2 diabetes, possibly due to improved insulin sensitivity.

Changes in Inflammatory Markers

In addition, Dr. Ciubotaru reported on a subgroup of 20 men in the trial in which supplementation resulting in plasma vitamin-D levels greater than 50 ng/mL was significantly associated with changes in inflammatory markers linked to gut-derived endotoxemia.

These included lipopolysaccharide (LPS), a marker of chronic low-grade inflammation, which binds to soluble CD14 (sCD14) and LPS-binding protein (LBP), both of which facilitate the intracellular transfer of LPS. Supplementation with vitamin D was associated with significantly increased levels of antibodies to LPS, indicating a decrease in the LPS-triggered inflammatory cascade.

Vitamin-D supplementation also resulted in a reduction in zonulin — when this protein is shed from the digestive-tract epithelium, it acts as an indirect measure of permeability, again suggesting a protective effect of vitamin D on the intestinal barrier.

Effect of Vitamin-D Supplementation on Gut Inflammatory Markers

Outcome P
Increase in sCD14 <0.003
Increase in LPS antibodies <0.037
Decrease in zonulin <0.01

Dr. Ciubotaru's dietary analysis also pointed to a role for caloric, fat, and fiber intake as important players in gut permeability and endotoxemia.

Dr. Ciubotaru and coauthors and Dr. Harmon reported no relevant financial relationships.

Joint Meeting of the International Society of Endocrinology and the Endocrine Society: ICE/ENDO 2014; June 23, 2014. Abstract OR34-2, Abstract MON-1056


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