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.

The investigators hypothesize that type-2 diabetes exacerbates the disruption of DC (dendritic cells)-mediated immune homeostasis associated with 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:

1. Subjects aged between 35 and 65 years
2. 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.
3. 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)
4. Non-smokers or former smokers ≥5 years after quitting

Exclusion Criteria:

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