Sex-specific correlation of IGFBP-2 and IGFBP-3 with vitamin D status in adults with obesity: a cross-sectional serum proteomics study

Nutr Diabetes. 2018 Oct 4;8(1):54. doi: 10.1038/s41387-018-0063-8.


Objective: Subjects with low vitamin D levels are at risk of cardiometabolic disease. The aim of this study was to identify novel serological markers linking vitamin D status with cardiometabolic profile in non-diabetic adults with obesity.

Methods: For the discovery phase, we used quantitative serum proteomics in sex-matched, age-matched and BMI-matched subjects with obesity [BMI: 25-35 kg/m2] and low [25(OH)D < 50 nmol/L] vs. high vitamin D status [25(OH)D > 50 nmol/L] (n = 16). For the validation phase, we performed ELISA in a larger cohort with similar characteristics (n = 179).

Results: We identified 423 and 549 differentially expressed proteins in the high vs. low vitamin D groups of the male and female cohorts, respectively. The small molecule biochemistry protein networks and the glycolysis|gluconeogenesis pathway were significantly enriched in the DEPs of both sexes. As surrogate markers to these processes, the insulin-like growth factor binding protein -2 (IGFBP-2) was upregulated in males, whereas IGFBP-3 was upregulated in females from the high Vitamin D status. This sex-specific trend was confirmed using Luminex ELISA to an independent but clinically analogous cohort of males (n = 84, p = 0.002) and females (n = 95, p = 0.03).

Conclusions: The high Vitamin D status correlated with the serological upregulation of IGFBP-2 in males and IGFBP-3 in females with obesity and may constitute surrogate markers of risk reduction of cardiometabolic disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Cross-Sectional Studies
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Protein 2 / blood*
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Male
  • Middle Aged
  • Obesity / blood*
  • Obesity / complications
  • Proteomics
  • Sex Factors
  • Vitamin D / blood*
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / complications


  • Insulin-Like Growth Factor Binding Protein 2
  • Insulin-Like Growth Factor Binding Protein 3
  • Vitamin D