Vitamin D Gene With High-Protein Diet Improves Glycemic Control

Veronica Hackethal, MD

October 07, 2015

People who carry a certain genetic variant called the T allele (vitamin-D–increasing allele) may show improved insulin resistance when they follow high-protein weight-loss diets, according to a new study published online September 29 in Diabetologia.

This is the first large, long-term randomized trial to show links between vitamin D genetic variants, dietary protein, and control of blood glucose, say the researchers. The work was carried out in obese and overweight individuals who did not have type 2 diabetes.

"Our data suggest that individuals carrying the [T] allele of vitamin D gene DHCR7 might have more benefit in improvement of insulin resistance than noncarriers by consuming high-protein weight-loss diets," commented author Yan Zheng, PhD, a research fellow at the Harvard TH Chan School of Public Health, Boston, Massachusetts.

"Our findings provide additional evidence for the role of vitamin D in insulin resistance [and] reinforce the view that dietary and genetic factors may act together to shape the effectiveness of weight-loss diets," he added.

Study Examined Three Vitamin D Metabolism Genes

Past studies have linked low levels of vitamin D to obesity, insulin resistance, and increased risk for type 2 diabetes. Studies have also identified several genetic variants involved in vitamin D metabolism. Although research is conflicting, some evidence has linked variants that result in low levels of vitamin D to increased risk of type 2 diabetes.

Foods high in protein and fat provide the main nutritional sources of vitamin D. Past studies have pointed to a role for vitamin D or other nutrients in regulating the expression of the vitamin D metabolism gene DHCR7, according to background information in the article.

In the study, researchers looked at three vitamin D metabolism genes:

  • DHCR7 — Helps make cholesterol, one of the building blocks of vitamin D.

  • CYP2R1 — Encodes the enzyme that converts vitamin D to its major circulatory form 25-hydroxyvitamin D, or 25(OH)D.

  • GC — Codes for vitamin D binding protein, a major player in vitamin D transport and storage.

For the research, overweight or obese individuals from the 2-year weight-loss study Preventing Overweight Using Novel Dietary Strategies trial (POUNDS Lost) were randomly allocated to low-fat, high-fat, low-protein, or high-protein diets. Genotyping was performed on 732 of them.

The association between genotype and change in body weight, fasting glucose, fasting insulin levels, and homeostasis model assessment of estimated insulin resistance (HOMA-IR) at 6 months (n = 656) and 2 years (n = 596) in response to the different diet types was examined. Eighty percent of participants completed the 2-year trial, and all diet groups experienced similar weight loss.

Results showed significant associations only between the DHCR7 gene, the high-protein diet, and changes in insulin and HOMA-IR at 6 months (P for interaction < .001) and 2 years (P for interaction ≤ .03).

There was no association between the vitamin D genotypes and the low-protein or fat-varied–diet groups.

Two-year results were similar but showed a weaker association. The authors note that adherence to the diet decreased between 6 months and 2 years, which could explain these later findings.

People who followed high-protein diets and carried the T allele of DHCR7 had significant decreases in fasting insulin (P = .0009) and HOMA-IR (P < .002). This interaction was not significant in participants who followed low-protein diets.

The CYP2R1 and GC genes showed no significant effects on body weight, fasting glucose, fasting insulin, or HOMA-IR in response to dietary protein or fats.

The researchers note that 80% of participants were white, so further studies are needed to explore ethnic differences in circulating vitamin D levels and associated genetic variants.

Observations Are Biologically Plausible

Although the mechanism underlying the association between high-protein diets, DHCR7, and improved blood glucose control remains unknown, it appears to be biologically plausible, according to the authors.

Protein-rich foods like fish, dairy, and meat (to a lesser extent) provide the main sources of naturally occurring vitamin D. In addition, dietary protein and amino acids play important roles in regulating glucose metabolism and insulin resistance.

So nutrients from protein-rich foods could affect the function of DHCR7, which in turn would affect vitamin D levels and insulin resistance.

"The implication of our study is that one effective way to benefit from weight-loss diets might be to choose the diets based on the participants' genetic background," Dr Zheng said.

And "although currently most patients cannot be tested for their vitamin D genotype, our findings may increase the awareness of interactions between genomic variation and environmental factors regarding human health among doctors and motivate further research in this area," he concluded.

The study was funded by grants from the National Heart, Lung, and Blood Institute; the Boston Obesity Nutrition Research Center; and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors report no relevant financial relationships.

Diabetologia. Published online September 29, 2015. Abstract


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.