Diabetes and oral diseases affect each other and hinder treatment

Research shows that common chronic diseases and problems associated with oral health have a detrimental and long-term reciprocal effect on each other. To achieve the best possible treatment outcomes, the general and oral health of patients should be considered as a whole.

In a study conducted at the University of Helsinki, the predictive value of oral health for the onset of various chronic diseases was investigated through a 10-year follow-up. A key finding was that periodontitis (a disease of the connective tissue of teeth) has a particular link with diabetes.

“We know from prior studies that periodontitis has a connection to many chronic diseases. Thanks to our exceptionally long-term dataset, we were able to analyse causalities and bidirectional effects between these factors,” says University Lecturer Pia Heikkilä.

“The research dataset was unusually extensive, encompassing some 70,000 study subjects, which increases the reliability and weight of the study,” she adds. 

The results of the study show that periodontitis, a common disease of public health importance in Finland, and apical periodontitis, inflammation of the apex of the tooth root, are associated with common metabolic diseases, such as metabolic syndrome, type 1 and 2 diabetes, and gestational diabetes, which require treatment. 

No similar association with other common chronic diseases, such as connective tissue diseases, rheumatoid arthritis, inflammatory intestinal diseases or serious mental diseases, was observed in the study.

The results have been published in the scholarly Frontiers in Oral Health journal.

A two-way effect – Severalfold costs

Based on the findings, a two-way effect exists between diabetes and other metabolic diseases, and periodontitis. Diabetes accelerates the progression of periodontitis and complicates its diagnosis and treatment, especially if diabetes has not been diagnosed or the disease is poorly controlled. 

Correspondingly, incipient or latent periodontitis makes diabetes chronic as well as hinders its diagnosis, control and maintenance therapy. 

The mutual effect of these diseases also results in increased costs, significant both in terms of public health and the economy.

“Based on our findings, successful treatment of periodontitis has a positive effect on the treatment outcomes for diabetes and reduces the cost of care. Similarly, the successful treatment of diabetes slows down the progression of periodontitis while reducing medical costs,” Professor Timo Sorsa notes. 

Health is the sum of several parts

The researchers estimate that more such bidirectional effects between diseases are likely to be identified in the future.

“The general and oral health of patients should be considered as a whole in healthcare, as our research demonstrates that even latent diseases have a harmful and long-term effect on one another,” Sorsa stresses.

“Hopefully, the training of professionals in the field and the healthcare service system in line with the health and social services reform in Finland will enable the collaboration needed for this. It’s in the interest of patients and taxpayers,” he concludes. 

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JOURNAL

Frontiers in Oral Health

DOI

10.3389/froh.2022.956072 

Gel treats gum disease by fighting inflammation

 

IMAGE: A TOPICAL GEL THAT BLOCKS THE RECEPTOR FOR A METABOLIC BYPRODUCT CALLED SUCCINATE TREATS GUM DISEASE BY SUPPRESSING INFLAMMATION AND CHANGING THE MAKEUP OF BACTERIA IN THE MOUTH. view more 

CREDIT: YUQI GUO

A topical gel that blocks the receptor for a metabolic byproduct called succinate treats gum disease by suppressing inflammation and changing the makeup of bacteria in the mouth, according to a new study led by researchers at NYU College of Dentistry and published in Cell Reports.

 

The research, conducted in mice and using human cells and plaque samples, lays the groundwork for a non-invasive treatment for gum disease that people could apply to the gums at home to prevent or treat gum disease.

 

Gum disease (also known as periodontitis or periodontal disease) is one of the most prevalent inflammatory diseases, affecting nearly half of adults 30 and older. It is marked by three components: inflammation, an imbalance of unhealthy and healthy bacteria in the mouth, and destruction of the bones and structures that support the teeth. Uncontrolled gum disease can lead to painful and bleeding gums, difficulty chewing, and tooth loss. 

 

“No current treatment for gum disease simultaneously reduces inflammation, limits disruption to the oral microbiome, and prevents bone loss. There is an urgent public health need for more targeted and effective treatments for this common disease,” said Yuqi Guo, an associate research scientist in the Department of Molecular Pathobiology at NYU Dentistry and the study’s co-first author.

 

Past research has linked increased succinate—a molecule produced during metabolism—to gum disease, with higher succinate levels associated with higher levels of inflammation. Guo and her colleagues at NYU Dentistry also discovered in 2017 that elevated levels of succinate activate the succinate receptor and stimulate bone loss. These findings made the succinate receptor an appealing target for countering inflammation and bone loss—and potentially stopping gum disease in its tracks. 

 

Strengthening the link between succinate and gum disease

The researchers started by examining dental plaque samples from humans and blood samples from mice. Using metabolomic analyses, they found higher succinate levels in people and mice with gum disease compared to those with healthy gums, confirming what previous studies have found. 

 

They also saw that the succinate receptor was expressed in human and mouse gums. To test the connection between the succinate receptor and the components of gum disease, they genetically altered mice to inactivate, or “knock out,” the succinate receptor. 

 

In “knockout” mice with gum disease, the researchers measured lower levels of inflammation in both the gum tissue and blood, as well as less bone loss. They also found different bacteria in their mouths: mice with gum disease had a greater imbalance of bacteria than did “knockout” mice.

 

This held true when the researchers administered extra succinate to both types of mice, which worsened gum disease in normal mice; however, “knockout” mice were protected against inflammation, increases in unhealthy bacteria, and bone loss.

 

“Mice without active succinate receptors were more resilient to disease,” said Fangxi Xu, an assistant research scientist in the Department of Molecular Pathobiology at NYU Dentistry and the study’s co-first author. “While we already knew that there was some connection between succinate and gum disease, we now have stronger evidence that elevated succinate and the succinate receptor are major drivers of the disease.”

 

A novel treatment

To see if blocking the succinate receptor could ameliorate gum disease, the researchers developed a gel formulation of a small compound that targets the succinate receptor and prevents it from being activated. In laboratory studies of human gum cells, the compound reduced inflammation and processes that lead to bone loss. 

 

The compound was then applied as a topical gel to the gums of mice with gum disease, which reduced local and systemic inflammation and bone loss in a matter of days. In one test, the researchers applied the gel to the gums of mice with gum disease every other day for four weeks, which cut their bone loss in half compared to mice who did not receive the gel.

 

Mice treated with the gel also had significant changes to the community of bacteria in their mouths. Notably, bacteria in the Bacteroidetes family—which include pathogens that are known to be dominant in gum disease—were depleted in those treated with the gel.

 

“We conducted additional tests to see if the compound itself acted as an antibiotic, and found that it does not directly affect the growth of bacteria. This suggests that the gel changes the community of bacteria through regulating inflammation,” said Deepak Saxena, professor of molecular pathobiology at NYU Dentistry and the study’s co-senior author. 

 

The researchers are continuing to study the gel in animal models to find the appropriate dosage and timing for application, as well as determine any toxicity. Their long-term goal is to develop a gel and oral strip that can be used at home by people with or at risk for gum disease, as well as a stronger, slow-release formulation that dentists can apply to pockets that form in the gums during gum disease. 

 

“Current treatments for severe gum disease can be invasive and painful. In the case of antibiotics, which may help temporarily, they kill both good and bad bacteria, disrupting the oral microbiome. This new compound that blocks the succinate receptor has clear therapeutic value for treating gum disease using more targeted and convenient processes,” said Xin Li, professor of molecular pathobiology at NYU Dentistry and the study’s lead author.  

 

Improved mineralized material can restore tooth enamel

 

 

IMAGE: SCIENTISTS TESTED THE EFFECTIVENESS OF THE NEW ENAMEL COATING ON REAL HEALTHY TEETH. view more 

CREDIT: ANASTASIA KURSHPEL / URFU

Scientists have perfected hydroxyapatite, a material for mineralizing bones and teeth. By adding a complex of amino acids to hydroxyapatite, they were able to form a dental coating that replicates the composition and microstructure of natural enamel. Improved composition of the material repeats the features of the surface of the tooth at the molecular and structural level, and in terms of strength surpasses the natural tissue. The new method of dental restoration can be used to reduce the sensitivity of teeth in case of abrasion of enamel or to restore it after erosion or improper diet. The study and experimental results are published in Results in Engineering.

"Tooth enamel has a protective function, but unfortunately, its integrity can be destroyed by, for example, abrasion, erosion or microfractures. If the surface of the tissue is not repaired in time, the enamel lesion will affect the dentin and then the pulp of the tooth. Therefore, it is necessary to restore the enamel surface to a healthy level or build up additional layers on the surface if it has become very thin. We have created a biomimetic (i.e., mimicking natural) mineralized layer whose nanocrystals replicate the ordering of apatite nanocrystals of tooth enamel. We also found out that the designed layer of hydroxyapatite has increased nanohardness that exceeds that of native enamel," says Pavel Seredin, Leading Specialist at UrFU Center "Nanomaterials and Nanotechnologies", Head of the Department of Solid State Physics and Nanostructures at Voronezh State University.

Hydroxyapatite is a compound that is a major component of human bones and teeth. Scientists selected a complex of polyfunctional organic and polar amino acids, including, for example, lysine, arginine, and histidine, which are important for the formation and repair of bone and muscle structures. The chosen amino acids made it possible to obtain hydroxyapatite, which is morphologically completely similar to apatite (the main component of tissues) of dental enamel. The researchers also described the conditions of the environment in which the processes of binding of hydroxyapatite to the dental tissue should occur. Only if these conditions are met it is possible to fully reproduce the structure of natural enamel.

"Traditionally in dentistry, composite restorative materials are used in enamel restoration. To increase the bonding efficiency of enamel and composite, the restoration technique involves acid etching of the enamel beforehand. The etching products left behind may not always have a positive effect on the bonding of enamel and synthetic materials. To reproduce the enamel layers with biomimetic techniques, we neutralized the media and removed the etching products using calcium alkali. In this way we improved the binding of the new hydroxyapatite layers," explains Pavel Seredin.

The formation of a mineralized layer with properties resembling those of natural hard tissue was confirmed by field emission electron and atomic force microscopy as well as by chemical imaging of surface areas using Raman microspectroscopy. The study was conducted on healthy teeth to eliminate the influence of extraneous factors on the resulting layer and to be able to compare the results with healthy teeth. Next, the researchers will tackle the challenge of repairing larger defects, which can be of varying nature from the initial stages of caries to cracks and volumetric fractures.

The joint research was conducted by scientists from the Research and Education Center "Nanomaterials and Nanotechnologies" of Ural Federal University, Voronezh State University, Voronezh State Medical University, Al-Azhar University, and the National Research Center (Egypt).

Reference

Tooth enamel consists mainly of an inorganic substance (biological apatite, about 95% by weight), an organic component (collagen fibers, 1-1.5%) and water (4%). Dental composite materials do not have the ability to bind physically and chemically to the dental tissues on their own. Therefore, additional materials must be used to create a strong bond between the composite and the tooth tissue. To increase the bonding effectiveness of enamel and composite, dental restoration technique involves acidic enamel pretreatment with a liquid or gel based on phosphoric acid (10-37%) or maleic acid (10%).

Hydroxyapatite is the main inorganic component of bone tissue, mineralized tissues of humans and animals, due to which it is widely used in various fields of medicine such as cosmetology, orthopedics, dentistry. Hydroxyapatite produced chemically, with the participation of a secondary source of calcium that is the egg shells of birds on the microelement composition, structure and size factor is similar to the apatite of dental enamel. This method of synthesizing hydroxyapatite is easy to use and economically feasible.

People who receive periodontal care have better outcomes after heart attack

The conventional wisdom is that medical and dental care are related, but less is known about how dental care relates to health outcomes after acute incidents like heart attacks.

 

To that end, University of Michigan researchers studied patients receiving periodontal care, dental cleanings or no dental care during 2016-2018 and who had acute myocardial infarction (heart attack) in 2017. 

 

They found that patients who had heart attacks and received periodontal maintenance care had the shortest length of stay in the hospital, and more follow-up visits. The longest length of stay was experienced by the no-dental-care group. 

 

"After controlling for several factors, the periodontal care group had higher odds of having post-hospital visits," said study co-author Romesh Nalliah, associate dean for patient services at the U-M School of Dentistry.  

 

There was no statistically significant difference between the other groups (active periodontal care and regular care) compared to the no-care group. 

 

The study, published in the Journal of the American Dental Association, did not establish a causal relationship between periodontal disease and heart disease, but research like this adds weight to the understanding that there is an association between oral health and overall health, Nalliah said.

 

There are 800,000 myocardial infarctions in the United States annually, and those with periodontal disease are at increased risk for hospitalization after a heart attack, he said. 

 

Nalliah and colleagues wanted to examine the association between periodontal care and heart attack hospitalization, and follow-up visits in the 30 days after acute care. Using the MarketScan database, they found 2,370 patients who fit the study criteria. Of those, 47% percent received regular or other oral health care, 7% received active periodontal care (root planing and periodontal scaling) and 10% received controlled periodontal care (maintenance). More than 36% did not have oral health care before they were hospitalized after a heart attack. 

 

"Dentistry is often practiced in isolation from overall health care," Nalliah said. "Our results add weight to the evidence that medical and dental health are closely interrelated. More and more studies like ours are showing that it is a mistake to practice medicine without the thoughtful consideration of the patient’s oral health."

 

Nalliah said improved communication between medical and dental teams could help with early intervention to ensure stable periodontal health in patients who have risk factors for heart disease. 

 

"It is important to include dental care in routine medical care and this means insurances must facilitate this connection rather than offer dental insurance as a separate add-on coverage," he said. 

 

Can good dental health help protect against cognitive decline and dementia?

 

An analysis of all relevant studies published in the medical literature indicates that poor periodontal health and tooth loss may increase the risk of both cognitive decline and dementia.

The analysis, which is published in the Journal of the American Geriatrics Society, included 47 studies. Poor periodontal health (reflected by having periodontitis, tooth loss, deep periodontal pockets, or alveolar bone loss) was associated with a 23% higher odds of cognitive decline and a 21% higher risk of dementia. Tooth loss alone was linked to a 23% higher odds of cognitive decline and a 13% higher risk of dementia. The overall quality of evidence was low, however.

“From a clinical perspective, our findings emphasize the importance of monitoring and management of periodontal health in the context of dementia prevention, although available evidence is not yet sufficient to point out clear ways for early identification of at-risk individuals, and the most efficient measures to prevent cognitive deterioration,” the authors wrote.

URL Upon Publication: https://onlinelibrary.wiley.com/doi/10.1111/jgs.17978

Dentistry study presents “positive stress” to boost tooth tissue regeneration

 

IMAGE: DR WARUNA L. DISSANAYAKA AND HIS RESEARCH TEAM BELIEVE THESE NEW FINDINGS WILL PROMOTE THE DEVELOPMENT OF NEW STRATEGIES TO ENHANCE THE THERAPEUTIC POTENTIAL OF TOOTH STEM CELLS. view more 

CREDIT: THE UNIVERSITY OF HONG KONG

Stress is typically thought of as a negative phenomenon, but researchers at HKU Dentistry found “positive stress” that can induce good changes in tooth stem cells to make them more resistant to injury and disease.

The study, published online in the Journal of Dental Research, is the first to show that adaptive mechanisms in tooth stem cells induced by preconditioning to stress can boost the tooth pulp tissue regeneration. The researchers found that oxidative stress caused by low-oxygen environment can elicit a protective response to make tooth stem cells less vulnerable to harm.

When a tooth is damaged, either by serious decay or injury, the living tissue inside becomes exposed to harmful bacteria and vulnerable to infection. Once the tooth pulp tissue is fully infected, current treatment options are limited to either removing the diseased pulp and filling the emptied canal with artificial materials such as rubber and cement or extracting the tooth. When a tooth core is filled with artificial inert materials, the pulp-less tooth dries out over time, becomes brittle and more prone to cracking and re-infection. This could eventually lead to extraction of the tooth and replacement with a prosthesis.

The research team led by Dr Waruna Dissanayaka, Assistant Professor in Oral Biosciences, aims to develop an approach to regenerate the lost tooth pulp which could revitalize the tooth and enable it to function like normal tooth.

Stem cell-based therapeutics has been considered a promising strategy in dental pulp regeneration. However, as the tooth root canal is surrounded by hard dental tissue with a limited blood supply, which creates a harsh environment for the cells with low-oxygen and nutrients, low cell viability after transplantation in vivo remains a critical challenge to researchers.

The research team developed a preconditioning protocol that modified the cells genetically to mimic a responsive state for low oxygen conditions in order to activate a protein that induce adaptive changes in the cells.

Dr Yuanyuan Han, a co-investigator of the team pointed out："As this protein was reported to activate several key adaptive mechanisms, we wondered whether this phenomenon can be applied to improve cell survival following transplantation until a sufficient blood supply is achieved."

"In our study, we found that these cells activate a metabolic mechanism to produce energy under low oxygen conditions and scavenge harmful metabolites produced in stress conditions.” Dr Han.  explained.

"Interestingly, we also found that preconditioned cells significantly enhanced the dental hard tissue formation within the regenerated pulp tissue." Dr Dissanayaka stated further.

"Former research has revealed that our cells possess number of adaptive mechanisms for stress, which are regulated by several key genes encoded in our DNA that are normally inactive," Dr Dissanayaka said. "If we can activate these genes, downstream expression of specific proteins can prime the cells less vulnerable to injury."

With the help of Dr Mohamad Koohi-Moghadam, Research Assistant Professor in Clinical Artificial Intelligence, the team investigated which genes are activated or repressed during preconditioning and is further working on to characterize the upregulated downstream proteins that make cells resistant to damage.

"Tooth stem cells have an inherent capacity to survive under stress" Dr Dissanayaka emphasized. "Our aim is to find ways to take advantage of this capacity and use positive stress to help regenerate the dental tissues."

Dr Dissanayaka plans to utilize the knowledge of specific genes and proteins responsible for inducing cell survival to identify drugs that can be used in clinical tissue regeneration. He believes these new findings will promote the development of new strategies to enhance the therapeutic potential of tooth stem cells.

The study won the IADR Colgate Research in Prevention Award at the 2022 IADR General Session. This project was funded by the General Research Fund of the Research Grants Council, Hong Kong.

Journal Article: “HIF-1α Stabilization Boosts Pulp Regeneration by Modulating Cell Metabolism” is published on Journal of Dental Research: HIF-1α Stabilization Boosts Pulp Regeneration by Modulating Cell Metabolism - PubMed (nih.gov)

Dental biorhythm is associated with adolescent weight gain

 

Research led by the University of Kent has discovered evidence of a biorhythm in human primary teeth that is associated with weight gain during adolescence.

 

An international research team led by Dr Patrick Mahoney at Kent’s School of Anthropology and Conservation discovered the biorhythm in primary ‘milk’ molars (Retzius periodicity [RP]) is related to aspects of physical development during early adolescence. A faster dental biorhythm produced smaller gains in weight and mass.

 

RP forms through a circadian-like process, occurring with a repeat interval that can be measured with a resolution of days. The rhythm relates to the period in which tooth enamel forms and is consistent within the permanent molars of individuals that do not retain evidence of developmental stress. The human modal RP has a near seven-day cycle but can vary from five to 12 days.

 

The first-of-its-kind research published by Nature Communications Medicine found that adolescents with a faster biorhythm (five or six-day cycle) weighed less, gained the least weight, and had the smallest change in their body mass index over a 14-month period compared to those with a slower biorhythm. Those with a slow biorhythm (seven or eight-day cycle) produced the greatest weight gain.

 

Dental histologists have known about the biological rhythm for over 100 years, but its significance for body mass and growth emerged recently in studies that compare mammalian species. Research has now focused on the meaning of the rhythm for humans.

 

One surprising finding was that participants with slower biorhythms were six times more likely to have a very high body mass index. Rapid change in body size is a natural consequence of adolescence, but excessive weight gain during puberty can have vast consequences for health such as obesity in adulthood.

 

Dr Mahoney said: ‘This research is an exciting first step. The next step is to determine if the link we have discovered extends to related adverse health outcomes for adults. Potentially, milk teeth may hold a record of this information many years before those outcomes can manifest in adults.’

 

Dr Gina McFarlane, a histologist on the project (also based at Kent), said: ‘Our findings provide a new avenue from which to explore links between overweight children and adult health risks. Milk teeth are naturally exfoliated (drop out) during the childhood years. These discarded teeth contain precise information about a fundamental growth rhythm that we now know tracks adolescent weight gain.’

 

The research paper titled ‘Dental biorhythm associates with adolescent weight gain’ is published by Nature Communications Medicine. doi: 10.1038/s43856-022-00164-x. This research project was funded by the Leverhulme Trust.

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JOURNAL

Communications Medicine

DOI

10.1038/s43856-022-00164-x