Disruption of Immune Homeostasis in Type 2 Diabetics With Generalized Chronic Periodontitis

Objectives: The primary objective of this study is to assess the short-term immune response of type-2 diabetics with generalized chronic periodontitis (GCP) to nonsurgical periodontal treatment.

Hypothesis: we hypothesize that type-2 diabetes exacerbates the disruption of DC-mediated immune homeostasis associated with periodontitis.

Subject population: Four groups comprising 80 subjects will be selected to participate: type 2 diabetics with GCP (n=20), prediabetics with GCP (n=20), normoglycemics with GCP (n=20) and healthy controls (n=20).

Study design: discovery study nested within a single-arm, single blinded clinical trial.

Experimental periods: Screening/Baseline Visit, Treatment Visit, 24 hours, 30 days and 3 months after treatment.

Intervention: Nonsurgical periodontal treatment will be conducted following a full-mouth approach; no antibiotics or chemical plaque control will be provided.

Primary outcomes:

• Cellular measures: Blood PBMCs- counts of myeloid DC (BDCA-1+CD19-), Plasmacytoid DC (cd123+cd303+) NK (CD56+CD16+), Th17, Treg (CD25+, CD39,CD73,CD127, cd152)
• Molecular measures: (Serum/crevicular fluid/ saliva): Anti-mfa-1 IgG (ELISA), Levels of IDO-1, TGFβ, TNFα, IL-1β, IL-6, IL-2, IL-10, IL-17, IL-23, IFNγ, CXCL12 (SDF1) by Multiplexing Luminex immunoassay [MAGPIX®]), performed in triplicate
• Expression on mDCs by custom qrt-PCR array (One step-fast cycle Taqman®, life technologiesTM of: angiopoietin-2, follistatin, GM-CSF, G-CSF, HGF, IL8, IL-6, leptin, PDGF-BB, PECAM-1, VEGF, TGFβ, IDO-1, IL-10, IL-1β, caspase-1, IL-17, IL-23, IL-23R IL-33, IL-12 p70, TRAIL, FOX01, Bcl-2, CXCL12 (SDF-1), CCL19, CCL21 analyzed in triplicate.
• Secondary outcomes: periodontal probing depth, periodontal attachment level, bleeding on probing, visible plaque and gingival bleeding.

Inclusion criteria

• Subjects aged between 35 and 65 years
• Subject diagnosed with T2DM (HbA1C ≥6.5), prediabetic (HbA1C ≥5.7 and ≤6.4) and non-diabetic (HbA1C ≤5.6) according to American Diabetes Association, 2013.
• Subjects with GCP (PPD ≥5 mm in ≥10 teeth and BOP in ≥30% of sites) and without GCP (PPD ≤4mm and BOP in <30% sites)
• Non-smokers or former smokers ≥5 years after quitting

Exclusion criteria

• Pregnant or lactating women
• Subjects taking medications known to affect the periodontium including phenytoin, cyclosporine
• Subjects with immunosuppressive conditions or diseases including HIV infection or Hepatitis (B, C).
• Subjects who require antibiotic prophylaxis for dental procedures.
• Subjects who have taken antibiotics in the last 6 months
• Subjects taking daily NSAIDS or on steroidal anti- inflammatory medications