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Overall assessment
This is a narrative review of the proposed two-way relationship between diabetes mellitus and periodontitis, with HbA1c treated as both a marker of glycaemic exposure and a possible connecting variable. It also reviews periodontal interventions that may improve periodontal disease and, to a lesser extent, glycaemic control.
Summary
Central argument
The paper argues that diabetes and periodontitis can reinforce one another:
- Diabetes, particularly poor glycaemic control, promotes periodontal inflammation, microbial dysbiosis, impaired tissue repair and tooth loss.
- Periodontitis may increase systemic inflammation and insulin resistance, thereby modestly increasing HbA1c.
- HbA1c therefore functions principally as an indicator of the severity of metabolic dysregulation, rather than as a molecular mediator in its own right.
The review reports that higher HbA1c is associated with more severe periodontitis, faster periodontal progression, alveolar bone loss and increased risk of tooth loss. It also notes evidence that people with periodontitis but without diagnosed diabetes may have slightly higher HbA1c than periodontally healthy controls.
Proposed mechanisms
The authors discuss several possible mechanisms.
1. Chronic inflammation and oral dysbiosis
Hyperglycaemia may alter salivary function, reduce buffering and cleansing, impair healing and favour pathogenic oral microbial communities. Periodontal inflammation may in turn contribute to systemic inflammatory signalling and insulin resistance.
2. Periodontal pathogens and insulin signalling
The paper highlights Fusobacterium nucleatum and Tannerella forsythia, reporting correlations between their abundance and fasting glucose or HbA1c. It cites experimental evidence that F. nucleatum products can activate TLR2–ERK pathways and interfere with IRS1/AKT signalling, potentially reducing hepatic glycogen synthesis and promoting insulin resistance.
3. DNA methylation and TET2
The review proposes that hyperglycaemia destabilises TET2, lowers 5-hydroxymethylcytosine and reduces DNA demethylation. This could alter the expression of inflammatory genes in periodontal tissue. It also discusses polymorphisms in TET2 and DNMT1 associated with periodontitis or HbA1c.
4. Reduced immunoregulatory signalling
Higher HbA1c is reported to correlate inversely with IL-10, FGF19 and LAP–TGF-β. The authors suggest that impaired anti-inflammatory regulation may link periodontal inflammation with poorer glycaemic control.
5. Platelet-rich fibrin
Higher HbA1c is associated with lower quantities and altered structure or cytokine content of platelet-rich fibrin, potentially compromising periodontal wound healing. This is presented as an interesting but preliminary mechanism.
Interventions
The strongest clinical section concerns non-surgical periodontal therapy, particularly scaling and root planing.
The review reports average HbA1c reductions of approximately:
- 0.4–0.5 percentage points at 3–4 months
- around 0.3 percentage points at 6 months
- possibly about 0.5 percentage points at 12 months in some analyses
The effect tends to be larger in people with higher baseline HbA1c and may diminish over time.
Adjuncts considered include:
- systemic antibiotics, particularly doxycycline;
- propolis;
- alpha-lipoic acid and melatonin;
- antimicrobial photodynamic therapy.
Photodynamic therapy may improve periodontal measures, but the review concludes that it has not clearly produced additional HbA1c lowering beyond scaling and root planing alone. The page 6 diagram explains the conventional Type I and Type II photochemical pathways through which photosensitisers generate radicals and singlet oxygen that damage bacterial DNA, lipids and proteins.
Novelty
The paper’s novelty is mainly integrative rather than evidential. It does not present new experiments, new patient data or a formal quantitative synthesis.
Its more distinctive contributions are:
1. Placing HbA1c at the centre of the review
Most reviews discuss the diabetes–periodontitis relationship broadly. This paper specifically organises the literature around HbA1c as:
- a marker of diabetes severity;
- a predictor of periodontal progression;
- a potential screening variable in people with periodontitis;
- an outcome that may improve following periodontal treatment.
However, the paper occasionally treats HbA1c as though it were mechanistically active. HbA1c is more accurately understood as an integrated biomarker of glycaemic exposure; hyperglycaemia, advanced glycation products, oxidative stress and inflammation are the likely active biological drivers.
2. Bringing together relatively disparate mechanisms
The review combines established mechanisms such as inflammation and oral dysbiosis with less commonly discussed topics:
- TET2-dependent DNA demethylation;
- DNMT1 polymorphisms;
- IL-10, FGF19 and LAP–TGF-β;
- changes in platelet-rich fibrin.
This combination is useful for hypothesis generation, although the strength of evidence varies substantially.
3. Including newer adjunctive therapies
Its discussion of indocyanine-green photodynamic or photothermal therapy gives the paper a contemporary clinical angle. It correctly distinguishes improvement in local periodontal outcomes from evidence for systemic HbA1c reduction.
Critique
1. It is not a systematic review despite using systematic-sounding language
The authors describe a database search and independent screening, but omit essential information:
- dates on which searches were performed;
- full reproducible search strings;
- number of records identified and excluded;
- reasons for exclusion;
- study-quality or risk-of-bias assessment;
- protocol registration;
- evidence-grading framework.
There is no PRISMA flow diagram and no structured appraisal of study quality. The review is therefore vulnerable to selective citation and publication bias.
2. The word “bidirectional” is stronger than the evidence presented
The evidence that diabetes worsens periodontal disease is considerably stronger than the evidence that periodontitis causes diabetes or materially worsens long-term glycaemic control.
A reduction in HbA1c after periodontal treatment is consistent with a causal effect, but it does not by itself prove a strong reciprocal disease mechanism. Possible explanations include:
- reduced systemic inflammation;
- temporary changes in diet after dental treatment;
- increased medical attention;
- improved medication adherence;
- regression to the mean;
- behavioural changes associated with trial participation.
The paper acknowledges conflicting studies, but its title and conclusions still convey more certainty than the underlying evidence warrants.
3. HbA1c is sometimes confused with a causal mediator
The paper repeatedly states that HbA1c “plays an important role” in the relationship. This is conceptually imprecise.
HbA1c is primarily:
- a biomarker of average glycaemic exposure;
- a predictor of diabetes complications;
- an outcome used to measure response.
It is not clear that glycated haemoglobin itself causes periodontal pathology. A more biologically accurate causal framework would emphasise:
- glucose exposure;
- advanced glycation end-products and RAGE signalling;
- oxidative stress;
- neutrophil dysfunction;
- microvascular impairment;
- altered collagen turnover;
- inflammatory cytokines.
The review would have been stronger had it separated HbA1c as measurement from hyperglycaemia as mechanism.
4. The epigenetic section contains speculative causal leaps
The TET2 argument moves through several separate observations:
- TET2 participates in demethylation.
- Hyperglycaemia can destabilise TET2 in some experimental contexts.
- Periodontitis is associated with altered methylation.
- Certain TET2 genotypes correlate with periodontitis or HbA1c.
These observations do not yet establish a continuous causal pathway from elevated glucose to TET2 impairment to inflammatory gene silencing to periodontitis.
There is also an apparent biochemical imprecision. The paper states that TET2 converts 5hmC “back to cytosine.” TET enzymes oxidise 5mC successively to 5hmC, 5fC and 5caC; restoration of unmodified cytosine usually requires additional base-excision repair or replication-dependent processes. TET2 does not simply perform a direct one-step conversion of 5hmC into cytosine.
5. Mechanisms with very different levels of evidence are presented together
Inflammation, impaired healing and microbial dysbiosis are supported by broad bodies of evidence. In contrast, the PRF hypothesis rests largely on ex vivo observations and small studies.
The review does not clearly classify mechanisms as:
- well established;
- plausible but incompletely validated;
- preliminary or speculative.
As a result, readers may overestimate the evidential status of the newer mechanisms.
6. The comparison with metformin is potentially misleading
The review states that a reported 0.72-percentage-point HbA1c reduction after scaling and root planing is comparable to metformin treatment. This is not a reliable head-to-head comparison because it draws estimates from different studies, populations, baselines and designs.
A cross-study comparison cannot establish therapeutic equivalence. Periodontal therapy should not be framed as a substitute for glucose-lowering medication, although it may provide a clinically useful adjunct in people who have periodontitis.
7. Antibiotic recommendations are too permissive
The conclusion suggests that systemic antibiotics provide additional therapeutic benefit. Yet the paper itself notes that the glycaemic benefit may not persist at six months.
The discussion gives insufficient attention to:
- antimicrobial resistance;
- adverse effects;
- microbiome disruption;
- patient selection;
- the need to reserve antibiotics for specific periodontal indications rather than routine HbA1c reduction.
8. Claims about propolis, melatonin and antioxidants exceed the certainty of the evidence
The review reports large effects from some adjunctive supplements while also noting low or moderate certainty. Large estimated effects in small, heterogeneous trials are particularly susceptible to publication bias and small-study effects.
These treatments should be described as investigational adjuncts, not established approaches for glycaemic control.
9. Confounding is insufficiently developed
Both diabetes and periodontitis are associated with numerous shared determinants:
- age;
- smoking;
- obesity;
- socioeconomic disadvantage;
- diet;
- healthcare access;
- medication use;
- oral hygiene;
- systemic inflammation.
The paper mentions observational limitations but does not adequately explain how residual confounding could generate or exaggerate apparent bidirectionality.
10. The clinical screening proposal is underdeveloped
The authors suggest that HbA1c could help predict diabetes in people with periodontitis and periodontal severity in people with diabetes. But they do not evaluate:
- sensitivity;
- specificity;
- positive predictive value;
- incremental value beyond age, BMI and family history;
- thresholds for referral;
- cost-effectiveness.
The proposal is reasonable, but not yet established by the review.
Bottom line
The paper is a useful, accessible overview of the diabetes–periodontitis literature and correctly highlights periodontal treatment as part of comprehensive diabetes care. Its most useful clinical conclusion is that non-surgical periodontal therapy can produce a modest, probably temporary improvement in HbA1c, particularly in people with poor baseline glycaemic control.
Its principal weakness is that it conflates three different things:
- HbA1c as a biomarker;
- hyperglycaemia as a biological exposure;
- periodontitis as a possible contributor to systemic insulin resistance.
The evidence supports a strong effect of diabetes on periodontal disease and a plausible but smaller reverse effect of periodontitis on glycaemic control. The proposed epigenetic, immune-regulatory and platelet-rich-fibrin mechanisms are interesting, but remain insufficiently integrated into a demonstrated causal chain.