White Blood Cell Signaling and Defense Mechanisms in Patients With Diabetes Mellitus Type 2 and Periodontitis

Human Polymorphonuclear Neutrophil (PMN) Cytosolic Signaling and Effector Functions in Patients With Diabetes Mellitus Type 2 and Periodontitis

White blood cell membrane and surface structures are affected by the metabolic disorders and complications found in diabetes mellitus. Therefore, cellular activation, signal propagation, intracellular signaling as well as bactericidal effector functions are altered.

When diabetic symptoms are corrected by the systemic intervention and treatment of the patients (Anti-diabetic Therapy/ADT, i.e. anti-diabetic medication, diet and dietetic supervision, physiotherapy and physical exercises), white blood cell functions will then normalize and reach the functionality comparable to those cells derived from healthy subjects.

Gum diseases like periodontitis have long been associated with and termed complications of uncontrolled diabetes mellitus. Vice versa, after diabetic conditions are corrected, periodontitis treatment will be proven effective, when oral hygiene regimen, full mouth decontamination (FD, i.e. the oral use of topical antiseptics prior and after professional mechanical tooth cleaning, tooth as well as root surface planing, polishing as well as gum and soft tissue decontamination in combination with systemic antibiotics) are performed. To reinforce gum healing, reinfection prevention (RP) as well as supportive periodontal therapy (SPT) will be administered by dental professionals on an individual basis and a detailed schedule.

If periodontal pockets critical for participant's self care are not eliminated by FD including RP and SPT, and niches >5mm after 6 month persist, patients are informed and offered surgical intervention as indicated for gum disease elimination.

Dental follow up exams will be offered to all participants.

Specific Aims

1. To investigate if cytosolic Ca2+- ( delta[Ca2+]i) and pH (delta_pHi) signaling responses and bactericidal effector functions of PMN dependent upon the status of diabetic control and are reduced or increased when compared to age and gender matched controls
2. To determine the biochemical basis for diabetic PMN alteration of motility as well as bactericidal functions: production of superoxide and release of elastase, respectively
3. To characterize the molecular basis of the observed alterations in the regulation of cytosolic calcium (delta[Ca2+]i) and pH (delta_pHi) exhibited by diabetic PMN
4. To investigate if the pre-activated state and altered bactericidal functionality of diabetic PMN are reversed when the patients' glycemic control is normalized, blood glucose levels as well as periodontal disease are corrected
5. To evaluate, if systemic and periodontal intervention can lead to clinical attachment gain in patients with diabetes mellitus type 2

Inclusion Criteria:

• Diabetes Mellitus, Type II
• Glycated Hemoglobin ≥8.5%
• Chronic Periodontitis
• Patients and controls should have at least 12 natural teeth (without subgingival fillings, crowns or caries)

Exclusion Criteria:

• Pregnancy
• Smoking
• Low Body Mass Index (BMI <18.5kg/m*m)
• Severe cardiovascular disease including coronary artery disease, cerebral vascular disease, peripheral vascular disease, valvular heart disease, and congestive heart failure
• Other major illnesses including cancer, liver disease, pulmonary disease, chronic infectious disease other than periodontitis (HIV, hepatitis, etc.), rheumatological disease, hematological disease, or any condition requiring hospitalization or chronic medical therapy other than diabetes.
• Major psychiatric illness requiring treatment, or that might interfere with the ability to understand or cooperate with the protocol
• Ongoing alcohol or drug abuse; all forms of medication or illegal substance abuse
• Systemic enteral or parenteral medication, in part daily vitamin or anti-oxidative supplementation and certain calcium channel blockers (i.e. Nifedipine); but anti diabetic drugs or insulin substitution
• Allergies to antibiotics or adjuvant medication / antiseptics as well as dental materials in use (including gloves) in particular those against topical antiseptic solutions i.e. chlorhexidine / N',N'''''-hexane-1,6-diylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)] or povidone iodine / 2-Pyrrolidinone, 1-ethenyl-, homopolymer, compound with iodine
• Severe dental disease defined as severe dental caries, and/or severe pulpal disease requiring surgical correction, or any other mucosal or dental condition not readily treated, or requiring extensive dental, oral surgical or prosthetic treatment, or any other oral treatment which could affect the outcome of periodontal therapy or diseases or syndromes that require systemic medication.
• Systemic, topical or inhaled steroid treatment for more than 30 consecutive days within 6 weeks of baseline.
• Any periodontal treatment within 6 months prior to baseline
• For controls: a periodontal screening index (PSI) > 1