State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
J Periodontal Res. 2019 Dec;54(6):671-680. doi: 10.1111/jre.12669. Epub 2019 Jun 19.
Serum 25-hydroxyvitamin D (25(OH)D ), 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)D deficiency and severity of T2DCP as well as the potential mechanisms.
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)D , 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.
Serum 25(OH)D 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)D 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)D quartile of 15-20 ng/mL (P = 0.007). The 25(OH)D 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.
Vitamin D 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)D deficiency may be related to the immune function of T2DCP by weakening PTPN2 signaling.
血清 25-羟维生素 D（25（OH）D）作为一种新出现的免疫调节剂，被认为与 2 型糖尿病牙周炎（T2DCP）有关。然而，影响 T2DCP 进展和严重程度的风险因素和改变表达的基因仍不清楚。因此，本研究旨在阐明 25（OH）D 缺乏与 T2DCP 严重程度之间的关系以及潜在的机制。
共纳入 182 名受试者，分为两组：无糖尿病的慢性牙周炎（P 组，n=88）和 2 型糖尿病伴牙周炎（DM+P 组，n=94）。两组患者根据年龄进一步分为青年（Y）和老年（E），共分为四组：P/Y、P/E、DM+P/Y 和 DM+P/E。通过探诊深度（PD）和临床附着丧失（CAL）评估牙周状况。采用酶联免疫吸附试验测定人 25（OH）D、白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α的血清水平。采用免疫组织化学法测定牙龈组织中蛋白酪氨酸磷酸酶非受体型 2（PTPN2）、维生素 D 受体（VDR）和 JAK/STAT 蛋白的表达。
DM+P 组血清 25（OH）D 水平低于 P 组（P<0.001）。当根据年龄对患者进行亚组分析时，DM+P/E 组中 25（OH）D 缺乏的比例高于 DM+P/Y 组（67% vs 51%），在 25（OH）D 四分位数为 15-20ng/ml 时差异有统计学意义（P=0.007）。DM+P 组中，25（OH）D 水平与空腹血糖（FBG）（r=-0.623）、血清 IL-1β（r=-0.392）、血清 TNF-α（r=-0.218）、PD（r=-0.269）和 CAL（r=-0.305）呈显著负相关（均 P<0.05），但与糖化血红蛋白（HbA1c）无相关性（P=0.123）。此外，DM+P 患者中 VDR 和 PTPN2 的表达水平降低，而 JAK1 和 p-STAT5 蛋白水平升高。
维生素 D 缺乏与 T2DCP 密切相关，年龄是其重要的中介因素。异常的 FBG 和 IL-1β 水平可能是 T2DCP 进展和严重程度的重要潜在危险因素。此外，25（OH）D 缺乏可能通过削弱 PTPN2 信号通路影响 T2DCP 的免疫功能。
