Diabetes Mellitus, Type 1 Clinical Trial
Official title:
Wound Healing After Tooth Extraction in Individuals With Type 1 Diabetes Mellitus
Dental treatment to individuals with diabetes mellitus, particularly type 1 diabetes (T1DM),
has always represented a challenge to the dentist. The literature provides some scientific
evidence showing that diabetes is a risk factor for the occurrence of oral opportunistic
infections, abnormal bone metabolism and delay in tissue repair, but with varying degrees of
evidence.
Hyperglycemia, as well as diabetes, are known as risk factor for post-surgical infections,
so maintaining the glycemic control in the postoperative period has been standard to health
care. However, there are few studies on the impact of the glycemic control in the repair
process after tooth extractions. And, to our knowledge, there aren't evidences that
infections resulting from oral surgery are more frequent in individuals with diabetes or
that the antibiotics prophylaxis is needed for these individuals before invasive dental
procedures.
Some prospective studies show that people with diabetes, especially type 2 (T2DM), do not
exhibit higher frequency of complications in repair process after tooth extractions compared
to healthy individuals without diabetes. Recently, the study conduct by Fernandes et al.,
2015, found higher frequency of delay on epithelial covering of the alveolus after 21 days
of tooth extraction in individuals with T2DM, comparing to a control group. Delay was not
related to infection and on the day 60th after surgery, all alveolus were totally
epithelized. One of the author's hypothesis for the delay in the alveolar epithelialization
on the participants with T2DM was the possible reduction of Epithelial Grow Factor (EGF) in
saliva of these individuals. Some studies already demonstrated the reduction in salivary
detection of EGF in individuals with diabetes.
There aren't prospective studies in the literature at our disposal, that evaluated
intraoperative complications of tooth extractions of teeth already erupted in individuals
with T1DM, or even post tooth extraction healing and the chronology of epithelialization of
the alveolus and its relation with the degree of salivary EGF.
The aim of this study is to evaluated the intraoperative events and the post- tooth
extraction healing, regarding the chronology of the repairing events and the occurrence of
postoperative complications in individuals with T1DM compared to a control group. Besides,
this study intend to relate the time of complete epithelial covering of the alveolus with
the EGF collected by whole stimulated saliva.
This prospective, longitudinal, case-control study will include 30 subjects with type 1
diabetes mellitus who require extraction of 1 or more erupted teeth, which will make part of
study group (SG). Other 30 healthy subjects, without diabetes mellitus, in need of tooth
extraction will make part of control group (CG). The groups will be matched by gender and
age.
This project will be submitted to the Research and Ethics Committee of Dentistry College in
University of Sao Paulo and all participants will sign a Consent Term.
All subjects who agreed to participate of this research will sign the Consent Term. A
questionnaire will be filled by the researcher, through information obtained by direct
questioning of the participant, contaning demographic data (gender, age), medical history,
dental history, medications and other health problems.
After anamnesis, the researcher will make a clinical evaluation of oral health to see the
necessity of tooth extractions. If there is any indication of tooth extraction, a periapical
radiograph will be performed. Also, will be required complimentary blood exams with blood
count, fasting glycemia and coagulation factors. Subjects that will be in use or that made
use antibiotics at least a month before the tooth extraction will be excluded from this
study.
On the day of the surgical procedure, will be measured, in the individuals of SG, quick
exams of glicated hemoglobin (A1C) through the equipment A1C Now+ Multi-Test HbA1c System
Bayer®. The glycaemia will be measured with the equipment Accu-Check®, before and after the
tooth extraction and in each appointment of post-surgery (Day 3, Day 7, Day 21, Day 60). The
blood pressure will also be measured before and after the tooth extraction.
The saliva collection will be performed before the surgical procedure, at least one hour
after the patient has fed. It will be collected stimulated saliva through the chewing of
parafilm. In the first minute the patient only will normally chew and swallow saliva, in the
next five minutes all saliva produced will be deposited in a graduated Falcon tube. Salivary
flow is going to be measured and expressed in mililiters per minute. The collected saliva
will centrifuged at 14000 rpm for 15 minutes. The supernatant will be collected and freeze
at -80oC and the sediment content will be discarded.
The saliva analysis for measuring the concentration of EGF will be carried out by
immunoassay using an EGF ELISA kit (Novex®). The EGF concentration is expressed by the
optical density reading of the samples compared to a standard curve, with the aid of a
microplate reader with an absorption of 450nm, followed by 570nm wavelength.
The Invitrogen human EGF kit is a solid phase sandwich Enzyme Linked-Immuno-Sorbent Assay
(ELISA). A polyclonal antibody specific for human EGF has been coated onto the wells of the
microtiter strips provided. Samples, including standards of known human EGF content, control
specimens, and unknowns, are pipetted into these wells.
During the first incubation, the Hu EGF antigen binds to the immobilized (capture) antibody
on one site. After washing, a biotinylated monoclonal antibody specific for Hu EGF is added.
During the second incubation, this antibody binds to the immobilized Hu EGF captured during
the first incubation.
After removal of excess second antibody, Streptavidin-Peroxidase (enzyme) is added. This
binds to the biotinylated antibody to complete the four-member sandwich. After a third
incubation and washing to remove all the unbound enzyme, a substrate solution is added,
which is acted upon by the bound enzyme to produce color. The intensity of this colored
product is directly proportional to the concentration of Hu EGF present in the original
specimen.
On the same day, after measuring blood pressure, glycaemia and A1C, and saliva collection,
the tooth extraction will be performed. No antibiotics will be prescribed before or after
surgery, as prophylactic function. Individuals of SG will be oriented to feed and administer
insulin normally. Subjects with abnormal laboratorial exams or abnormal glycaemia (under 70
or above 400) will re-evaluated and the tooth extraction post-pone.
The tooth extractions will be performed by the same dentist with experience in minor oral
surgery, in the Special Care dentistry center of the Dental School of University of Sao
Paulo. The subjects of both groups who agreeded to participate will be submitted by
conventional extraction technique, which is the same technique for any other patient of the
Center. The participants will receive the same intervention of tooth extraction of patients
who are not enrolled in the study, as following: after the anesthetic block will be held
sindesmotomy, taking off the periodontal, tooth dislocation with the aid of lifts and
removal of the tooth with forceps. The surgical technique will be modified depending on the
condition of the tooth in the alveolus, performing dental section or osteotomy when
necessary. Finally, curettage of the socket will be held and a simple suture with silk
thread 3-0.
At the end of surgery, the blood pressure and glycaemia will be measured again. Information
of the surgery procedure will be recorded, such as the tooth that was extracted, the reason
of tooth was extracted (caries, periodontal disease, orthodontic needed), time spent on the
surgery, number of anesthetic tubes and complications.
It will be asked for the participants to press with a gauze the alveolar region for 30
minutes to control bleeding. It will be prescript only analgesic, every 8 hours, for 3 days,
in case of pain. The participant will receive postoperative written instructions.
Evaluation of repair and possible complications of the surgical wound will be held in 4
different moments, on day 3, 7, 21 and 60 after surgery. These evaluation it will always be
perform by the researcher, trained and calibrated. Will be observed signs and symptoms such
as edema, erythema, bone exposure, fever, pain and analgesic need. Glycaemia will be
measured in all appointments from individuals from SG. Digitalized periapical radiograph
will be performed at the days 7 and 60.
The repair process will be considered late when the following events do not match the period
considered normal: day 3- alveolus filled by blood clot and fibrin; day 7- alveolus filled
with granulation tissue; day 21- complete epithelialization of the wound; day 60- alveolus
exhibiting bone deposition, radiographically observed. In case of delay in complete
epithelialization after day 21, the subject will be accompanied by further consultations
every 7 days for evaluation. If there is a delay in the alveolar bone deposition in the day
60, the subject will undergo another monitoring at day 90 for new radiography and
evaluation.
In case of post-extraction infection (alveolitis), will set up the recommended treatment
described by Kaya et al., 2011, with removal of infected debris, with abundant irrigation
with saline 0.9% NaCl and curettage. It will also be prescribed antibiotics, Amoxicilin
500mg or Clindamicin 300mg, every 8 hours for 7 days, and anti-inflammatory, Nimesulide
100mg, every 12 hours for 5 days (Barasch et al., 2008).
The pain will be evaluated and assessed at the time of each appointment, through the Visual
Analogue Scale (VAS), that consists of direct questioning to the patient and a visual
demonstration of the scale (Annex A), being zero the total absence of pain and ten the
maximum bearable level of pain by the patient.
After 60 days of surgery, the post-operative will be classified as: without complications or
with complications, according to the presence or absence of signs and clinical symptoms
observed. It will also be classified in: without delay and delay, according to the
chronology of repair observed. According to Cheung et al., 2001, the following situations
will be considered as post-operative complications:
- Acute alveolar infection: characterized by pain, erythema, edema, purulent secretion
and fever;
- Acute inflammation of the alveolus: characterized by pain, inflammation, perialveolar
tissue, but without purulent secretion and no fever;
- Alveolitis: characterized by persistent throbbing pain and bone exposure. All data will
be transferred to an Excel spreadsheet and analyzed descriptively and associated with
each other. Complications will be compared between the two groups. Additionally, in the
study group, we will investigate if the occurrence of complications was related to A1C,
glycaemia at surgery day, as well as EGF of saliva.
Will be held in all subjects (SG and CG) at least 3 periapical radiographs through
paralleling technique, for each tooth requiring extraction. The first radiograph will be
performed at the time of anamnesis, with conventional radiographic film in order to diagnose
the need for extraction and assess the condition of the tooth. The second and third
radiographs will be carried out using a digital sensor, at day 7 and day 60, using the
digital device Soredex DIGORA Optime®, to evaluate the alveolar bone repair by grayscale
concentration captured.
For standardization of these 3 X-rays of the same tooth in the same subject, a bite record
of each subject will be carried out with silicone and will always be used to take the
radiograph. The alveolus will be considered repaired and without delay when, at the day 60,
show complete bone deposition.
;
Observational Model: Case Control, Time Perspective: Prospective
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