Relationship between serum 25-hydroxyvitamin D3 levels and severity of chronic periodontitis in type 2 diabetic patients: A cross-sectional study

J Periodontal Res. 2019 Dec;54(6):671-680. doi: 10.1111/jre.12669. Epub 2019 Jun 19.


Background and objectives: Serum 25-hydroxyvitamin D3 (25(OH)D3 ), a newly emerged immune regulator, is considered to be involved in type 2 diabetic periodontitis (T2DCP). However, the risk factors and genes with altered expression that influence the progression and severity of T2DCP remain unknown. Accordingly, the aim of the present study was to elucidate the relationship between 25(OH)D3 deficiency and severity of T2DCP as well as the potential mechanisms.

Material and methods: A total of 182 subjects were divided into two groups: chronic periodontitis without diabetes (P group, n = 88) and type 2 diabetes mellitus with periodontitis (DM+P group, n = 94). Patients in both groups were further classified according to age as young (Y) and elderly (E) for a total of four groups: P/Y, P/E, DM+P/Y, and DM+P/E. Periodontal status was evaluated based on the probing depth (PD) and clinical attachment loss (CAL). The serum levels of human 25(OH)D3 , interleukin (IL)-1β, and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assays. Immunohistochemistry was used to measure the expression of protein tyrosine phosphatase non-receptor type 2 (PTPN2), vitamin D receptor (VDR), and JAK/STAT proteins in the gingival tissue.

Results: Serum 25(OH)D3 levels were lower in the DM+P group than those in the P group (P < 0.001). When the patients were subgrouped according to age, 25(OH)D3 deficiency was more commonly found in DM+P/E than in DM+P/Y (67% vs 51%), with a significant difference detected in the 25(OH)D3 quartile of 15-20 ng/mL (P = 0.007). The 25(OH)D3 level showed a significant negative correlation with fasting blood glucose (FBG) (r = -0.623), serum IL-1β (r = -0.392), serum TNF-α (r = -0.218), PD (r = -0.269), and CAL (r = -0.305) in the DM+P group (all P < 0.05), but not with hemoglobin A1c (P = 0.123). Additionally, reduced VDR and PTPN2 expression levels were observed in DM+P patients, whereas JAK1 and p-STAT5 protein levels were increased in this group.

Conclusions: Vitamin D3 deficiency is strongly associated with T2DCP, and age mediates this relationship. Abnormal FBG and IL-1β levels should be considered as important potential risk factors for the progression and severity of T2DCP. Moreover, 25(OH)D3 deficiency may be related to the immune function of T2DCP by weakening PTPN2 signaling.

Keywords: IL-1β; PTPN2; age; diabetic periodontitis; fasting blood glucose; vitamin D3.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Calcifediol
  • Chronic Periodontitis / blood*
  • Chronic Periodontitis / complications
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Female
  • Gingiva / metabolism
  • Humans
  • Interleukin-1beta / blood
  • Male
  • Middle Aged
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 / metabolism
  • Receptors, Calcitriol / metabolism
  • Risk Factors
  • Tumor Necrosis Factor-alpha / blood
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Young Adult


  • IL1B protein, human
  • Interleukin-1beta
  • Receptors, Calcitriol
  • Tumor Necrosis Factor-alpha
  • VDR protein, human
  • Vitamin D
  • 25-hydroxyvitamin D
  • PTPN2 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2
  • Calcifediol