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Niigata University clarify the mechanisms behind delayed dental nerve healing in patients with type 1 diabetes


A research group at Niigata University characterized the mechanism by which patients with type 1 diabetes experience delayed healing in dental nerve treatment, as compared to patients without the disease. Compared to unaffected people, patients with diabetes had fewer cells necessary for tooth repair. Moreover, the balance of macrophages in patients with diabetes was biased toward those that promote inflammation. The research team is examining if a similar phenomenon occurs in type 2 diabetes and hopes to establish a new treatment approach.

Type 1 diabetes is common in children. In this condition, autoimmunity destroys the cells that secrete insulin (a hormone that controls blood sugar levels). This lack of insulin damages blood vessels in the entire body and body organs. Compared to unaffected people, patients with type 1 diabetes are more prone to tooth decay and periodontal disease. This is particularly problematic in patients presenting with dental cavities having reached nerves because the standard cure is less effective and nerve preservation is difficult.

The research was conducted by Assistant Professor Naoto Ohkura of the Division of Cariology, Operative Dentistry and Endodontics, Department of Dentistry at Niigata University and his research group. They aimed to clarify the cause of delayed healing in patients with type 1 diabetes compared with unaffected people. They performed the research assuming that clarifying the cause of the delay will contribute to the development of appropriate treatments.

Ohkura first used a rat with a decayed back tooth on the upper left side, partially penetrating into the nerve. The experiment used a method called direct pulp capping. After making a small hole in the tooth under a microscope and removing part of the nerve, he inserted dental cement called mineral trioxide aggregate (MTA), which is known to be highly alkaline and has sterilizing properties. He then covered the hole with composite resin, a photocoagulation plastic, to prevent saliva and bacteria contamination, and directly observed the nerve under the MTA cement.

Schematic diagram of the animal experiment. The method used in human dental treatment was applied to rats.
Provided by Assistant Professor Naoto Ohkura

Ohkura examined approximately 20 rats and observed that odontoblasts (dentin bud cells) appeared and were active in the nerves of healthy rats; however, the rats with type 1 diabetes showed almost no odontoblasts. While teeth with viable nerves have repair ability that is originally provided by cells, this capacity appeared to be impaired in the rats with type 1 diabetes.

The researchers subsequently investigated the distribution of macrophages with immune function. In healthy rats, they observed a lower number of M1 macrophages that cause inflammation within the nerves and a higher number of M2 macrophages which had repair functions. However, the rats with type 1 diabetes showed a disrupted macrophage balance, in which M1 macrophages were predominant. Consequently, healthy tooth structure was not formed, and the treatment was not successful.

Different distributions of macrophages in the dental nerves of type 1 diabetic (left) and healthy (right) rats, as revealed by experimental findings.
Provided by Assistant Professor Naoto Ohkura

The development of regenerative medicine has allowed the practice of "regenerative endodontic therapy" in some cases, in which cells taken from one's own wisdom tooth are grown and used to repair cavities. Ohkura stated, "It is rare that a patient with diabetes has wisdom teeth with no inflammation; thus, this is not a realistic treatment." He also pointed out that, "If a method to properly induce the differentiation of M1 and M2 macrophages or a method to generate odontoblasts can be established, it might increase the chances of a successful treatment." As a medical doctor with a pharmacist's license, he says, "I hope that a drug suitable for dental cures will be developed. I hope that we will someday be able to treat cavities with medicine.''

Patients with type 2 diabetes are similarly susceptible to tooth decay, and their nerve treatments often do not improve the condition. Many of Ohkura's patients in the outpatient department continue to have a chief complaint that the feeling of discomfort never goes away. He will continue to examine if a similar mechanism is responsible for delayed dental healing in patients with type 2 diabetes.

The research was supported by Grants-in-Aid for Scientific Research. The results were published in the electronic version of the American dental journal Journal of Endodontics on November 7, 2023, and announced by Niigata University on November 22, 2023.

Original article was provided by the Science Portal and has been translated by Science Japan.

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