• Neuregulin-4 in the GCF [ Time Frame: 6 month ]
  Measured by Enzyme-Linked Immunosorbent Assay in μL
• The receptor ErbB4 in the GCF [ Time Frame: 6 month ]
  Measured by Enzyme-Linked Immunosorbent Assay in μL
• Neuregulin-4 in the saliva [ Time Frame: 6 month ]
  Measured by Enzyme-Linked Immunosorbent Assay in μL
• The receptor ErbB4 in saliva [ Time Frame: 6 month ]
  Measured by Enzyme-Linked Immunosorbent Assay in μL

• Pocket depth [ Time Frame: 6 month ]
  Measured by Manual UNC periodontal probe in mm
• Clinical attachment level [ Time Frame: 6 month ]
  Measured by Manual UNC periodontal probe in mm
• Bleeding on probing [ Time Frame: 6 month ]
  Measured by Manual UNC periodontal probe by gently probing the orifice of the gingival crevice, the periodontal probe will be inserted 1 to2 mm into the gingival sulcus starting at one interproximal area and moving to the other. If bleeding occurs within 10 seconds a positive finding is recorded.
• plaque index [ Time Frame: 6 month ]
  Measured by Manual UNC periodontal probe Scores: 0: No plaque

  1. A film of plaque adhering to the free gingival margin and adjacent area of the tooth. The plaque may be seen in situ only after application of a disclosing solution or by using the probe on the tooth surface.
  2. Moderate accumulation of soft deposits within the gingival pocket, or the tooth and gingival margin, which can be seen with the naked eye.
  3. Abundance of soft matter within the gingival pocket and/or on the tooth and gingival margin.
• Glycosylated Haemoglobin (HbA1c %) [ Time Frame: 6 month ]
  Measured by High performance liquid chromatography in mmol/mol
• Fasting plasma Glucose Level (FPG) [ Time Frame: 6 month ]
  Measured by blood sampling in (mg/dl)
• Body Mass Index (BMI) [ Time Frame: 6 month ]
  Measured in (Kg/m2)

The aim of this study is to measure the levels of Nrg4 and ErbB4 in the GCF and saliva of periodontitis stage III and IV patients with and without type 2 diabetes mellitus and to correlate their levels with the periodontal clinical parameters and the blood glucose levels including the fasting plasma glucose level (FPG) and glycated hemoglobin (HbA1c).

This study will be conducted in the Oral Medicine and Periodontology department, Faculty of Dentistry- Cairo University, Egypt.

Patients will be selected from the outpatient clinic of the department of Oral Medicine and Periodontology, Faculty of Dentistry-Cairo University.

Dental patients will be recruited in a consecutive manner from the clinic of the department of Oral Medicine and Periodontology, Faculty of Dentistry -Cairo University.

Medical history and dental history will be taken; thorough oral examination will be done.

The aim of the study will be explained to the patient and the patient's acceptance to participate in the survey will be received.

Non-respondent patients or patients refusing to participate will be reported with the cause of their refusal.

Conventional oral and periodontal examination will be held on a dental unit using the light of the unit, mirror and probe

• Periodontitis
• Diabetes Mellitus

Inclusion Criteria:

• For periodontitis stage III and IV patients according to (Papapanou et al., 2018 and Tonetti et al., 2018)

  1. Bleeding on probing (BOP) ≥ 30%.
  2. At least four non-adjacent teeth sites in each jaw having CAL ≥ 5 mm and PD ≥ 6 mm in one or more sites.
  3. Tooth loss due to periodontitis ≥ 5 teeth.
  4. Presence of a minimum of 15 natural teeth. For diabetes and non-diabetic patients according to ("Diagnosis and Classification of Diabetes Mellitus," 2014)
  5. Patients with type 2 diabetes mellitus will be diagnosed as having type 2 diabetes mellitus ≥ 5 years before the study and treated with stable doses of oral hypoglycaemic agents and/or insulin under the supervision of an endocrinologist with their glycated haemoglobin level (HBA1c) > 6%.
  6. Non diabetic Patients in the control and stage III and IV periodontitis groups will be selected as having Fasting plasma glucose (FPG) <126 mg/dL.

Exclusion Criteria:

1. Individuals with any known systemic disease other than type 2 diabetes.
2. Pregnant and lactating women.
3. Individuals that received periodontal treatment within the last 6 months.
4. Individuals with a history of systemic antibiotics and anti-inflammatory drugs within the last 3 months.
5. Former or current smokers.