Resumen de Proteolytic Mediators in Gestational Diabetes Mellitus and Gingivitis

Pinar Gümüs, Özgün Özçaka, Banu Ceyhan-Öztürk, Taina Tervahartiala, Heidi Husu, Anna Maria Heikkinen, Timo Sorsa, Nurcan Buduneli

• Background: This study evaluates levels of matrix metalloproteinase (MMP)-8, MMP-9, and tissue inhibitor of MP-1 (TIMP-1) in biofluids of women with gestational diabetes mellitus (GDM) and systemically healthy counterparts with different statuses of periodontal health.

  Methods: Seventy-one women with GDM and gingivitis (Gg), 30 women with GDM and healthy periodontium (Gh), 28 systemically and periodontally healthy women (Hh), and 37 systemically healthy women with gingivitis (Hg) were evaluated. MMP-8, MMP-9, and TIMP-1 levels were determined in gingival crevicular fluid (GCF), saliva, and serum by immunofluorometric and enzyme-linked immunosorbent assays. Full-mouth clinical periodontal parameters were recorded.

  Results: GCF and serum MMP-8 concentrations, serum MMP-9 concentrations, and serum MMP-8/MMP-1 and MMP-9/MMP-1 molar ratios were significantly higher in Gg compared with Hg group (P <0.05). Serum MMP-8 levels and salivary TIMP-1 levels were higher in Gh compared with Hg group (P <0.05) whereas salivary MMP-8/TIMP-1 molar ratio was lower in Gh compared with Hg group (P <0.05). Elevated concentrations of GCF MMP-8 and MMP-9 were found in Gg compared with Gh group (P <0.05). Significant correlations were found between local levels of biomarkers and clinical periodontal parameters in only GDM group.

  Conclusion: GDM may modulate both local and circulating levels of MMP-8 especially when associated with gingivitis.

  Gestational diabetes mellitus (GDM) is a type of DM diagnosed in the second or third trimester of pregnancy that exerts maternal and neonatal risks.1 There is a plethora of evidence on the reported association between periodontal disease and increased risk of systemic diseases such as cardiovascular disease (CVD) and DM.2-5 Presence of an inflammatory condition (e.g., gingival inflammation) and infection (e.g., oral bacterial load) may be associated with GDM pathogenesis.6 Possible influence of persistent gingival inflammation on the local and systemic immune response of pregnant women with DM was investigated recently.7 Moreover, immunologic aspects, bacterial infection, and systemic inflammation were evaluated, and positive associations were reported.8 Activation of inflammatory pathways in GDM may pose a risk for development of type 2 DM (DMt2) and CVD, which are important future long-term complications of GDM.9 Periodontopathogenic bacteria and their virulence factors activate host immune-inflammatory response by increasing inflammatory cells and matrix metalloproteinases (MMPs) that can cause gingival inflammation.10 Although exact mechanisms have not been clarified yet, the relationship between DM and MMP activity has been associated with vascular complications.11 The possible mechanism has been explained by pathologic remodeling of extracellular matrix (ECM) results in structural changes of vascular structures in patients with DM.12 Moreover, accumulation of advanced glycation end products (AGEs) has been reported to be associated with reductions in ECM turnover due to hyperglycemia.13 In an AGE-rich environment, abundance of glucose-derived cross-linked structures (collagen or lipid) leads to ECM deposition in capillary and arteriolar basement membranes that contribute to pathogenesis of vascular complications of DM.14 It has been suggested that existing inflammation and infection may be a confounder in pathogenesis of GDM.15 Possible AGE interactions in patients with DM have been reported to exhibit impaired neutrophil function and altered collagen metabolism leading to an elevated inflammatory state.2 Neutrophils are major sources of MMP-8 and MMP-9, and large amounts of these destructive enzymes are produced in inflamed tissues.16 Although innate immunity is stimulated, adaptive immunity is comparably suppressed during pregnancy.9 Investigation of local and circulating levels of MMPs, as part of the innate immunity, may provide further insight to their possible role in the pathogenesis of GDM.

  It has been hypothesized that the systemic immune response of patients with periodontal disease may predispose or exacerbate other systemic inflammatory processes2 and, hence, perpetuate the existing insulin resistance (IR) of women with GDM. Therefore, the aim of the present study is to investigate gingival crevicular fluid (GCF), saliva, and serum levels of MMP-8, MMP-9, and tissue inhibitor of MP-1 (TIMP-1) in women with GDM and systemically healthy counterparts with or without gingivitis.