Real-world evidence for herbal medicine benefit in 9728 type 2 diabetes patients-peridonotitis risk and ambulatory care utilization

Abstract

BACKGROUND

Recent evidence manifests that individuals with type 2 diabetes (T2D) are increasingly affected by oral disorders. Although medicinal herbs have shown promise in managing T2D, their benefit in managing periodontitis risk and subsequent healthcare utilization remains uncertain.

AIM

To compare risk of periodontitis and associated ambulatory care utilization among individuals with T2D who did or did not receive add-on medicinal herbs.

METHODS

We included individuals aged 20-70 years with newly diagnosis of T2D and being free of periodontitis in 2000 and 2010. Periodontitis events were tracked from cohort entry until December 31, 2013. The association between medicinal herb use and periodontitis risk was assessed by multivariate Cox regression, while differences in periodontitis-related ambulatory care were analyzed using Mann-Whitney U test.

RESULTS

After propensity score matching, 9728 individuals were included in both the herbal and non-herbal groups. Those who used herbs for more than two years experienced a potently lower risk of periodontitis by 52%. Compared to herb users, the non-users substantially incurred higher frequency and cost of periodontitis-related ambulatory visits post-diagnosis, and the costs per ambulatory visit increased with time after periodontitis onset.

CONCLUSION

The rollout of this study not only tackled the former research gap but also provided an insight that the combination of medicinal herbs may take into account while planning holistic and individualized oral health care for T2D persons.

Key Words: Type 2 diabetes; Periodontitis; Medicinal herbs; Cohort study; Interdisciplinary collaboration; Risk

Core Tip: As periodontitis is a common and frequently occurring condition following type 2 diabetes (T2D) onset and insidiously triples cardiorenal mortality in individuals with diabetes, we conducted a population-based cohort study to gain deeper insight into the relationship between medicinal herb use and incident periodontitis. In this study, adding medicinal herbs to routine care for more than 2 years benefited T2D individuals by lowering periodontitis risk as much as 52%; moreover, this approach substantially reduced the subsequent use of periodontitis-related ambulatory services, underscoring the increasing importance of interdisciplinary healthcare.

INTRODUCTION

Though progress in treatment strategies has increased life expectancy, human beings are still susceptible to chronic illnesses due to innate inflammatory responses that gradually undermine health[1]. When mediators like antigen load exceed the body’s internal tolerances, excessive inflammation can lead to increased sympathetic outflow, contributing to metabolic dysfunction, as observed in type 2 diabetes (T2D). By a recent report, the global prevalence of T2D is projected to rise from 5.9% in 2021 to 9.5% in 2050, representing a 61.2% increase[2]. In that case, the burgeoning incidence of diabetes could push the healthcare system toward a critical tipping point. According to a national survey in the United States, the average annual medical expenditure per T2D patient was USD 19736, approximately three times the cost for a person without T2D (USD 7714)[3]. By and large, the total national costs imposed by diabetes are expected to increase from USD 322 billion in 2012 to USD 413 billion in 2022, reflecting a 28% rise over the past decade[3,4].

Not only does T2D result in considerable economic strain, but it also poses serious physiological consequences due to persistent hyperglycemia, such as periodontitis, a commonly observed oral disease that significantly reduces quality of life in individuals with T2D[5]. Today, extensive epidemiological data show a clear association between hyperglycemia severity and periodontitis progression. A recent systematic review of 53 epidemiological reports confirmed that diabetes was a major risk factor for periodontitis; susceptibility was nearly 40% higher in people with T2D[6]. Furthermore, an 11-year longitudinal follow-up found that severe periodontitis tripled the annual risk of death from cardiorenal causes (including ischemic heart disease and diabetic nephropathy) among individuals with T2D[7]. It is assumed that the presence of pro-inflammatory profiles accompanying hyperglycemia may affect the salivary glands, bacterial colonization, and worsen the gingival index[8]. Moreover, some processes caused by aberrant inflammatory responses may also intervene, such as the activation of osteoclasts leading to bone resorption[9,10]. Though some mechanisms reportedly to contribute to this crosstalk thus far, there remains a lack of curative approaches to this condition. These challenges may have ushered in an era of complementary therapeutic possibilities in managing T2D patients.

Known for the advantage of fewer side effects, medicinal herbs, a specialized therapy within traditional Chinese medicine, have been widely applied to treat human diseases. Some evidence suggests that the use of medicinal herbs significantly reduces fasting blood glucose levels in diabetic patients. For example, an earlier review has shown that combining existing therapeutic agents with medicinal herbs had a more favorable effect on lowering blood glucose and modulating intrinsic inflammatory reactions than monotherapy with anti-hyperglycemic agents[11]. Another animal study reported that Ji-Sheng-Shen-Ci-Wan was as effective as metformin, and administering both treatments for one month was more efficient than metformin alone in enhancing hypoglycemia and insulin sensitivity in T2D mice induced by a high-fat diet and streptozotocin[12]. In addition to improving glucolipid metabolism, this herbal formula was also shown to alleviate osteoporosis in ovariectomized mice by mitigating osteoblast pyroptosis[13,14]. As a segment of the inflammatory programmed cell death pathway, pyroptosis plays an indispensable role in the pathogenesis of periodontitis[15]. Taken together, we postulate that medicinal herbs may regulate gene expression to prevent or delay the emergence of periodontitis during T2D treatment. Nevertheless, global understanding of this issue remains limited. This population-based study aims to clarify the risk of periodontitis and associated ambulatory care utilization among individuals with T2D who use medicinal herbs compared with those who do not. Beyond addressing a research gap, this investigation provides an empirically derived framework for shaping health policies and designing tailored treatment programs for these individuals.

MATERIALS AND METHODS

Data source

All relevant data for this retrospective follow-up cohort study were retrieved from the National Health Insurance (NHI) Research Database in Taiwan. This database is a continuous, multistage sampling data bank managed by the Health and Welfare Data Science Center. All deposited data include beneficiary information such as gender, birth date, and physician billing records for comprehensive outpatient and inpatient visits covered by the NHI program. As of now, over 99% of Taiwan’s population is registered in this program[16]. To protect privacy, the identification numbers of individuals and healthcare facilities in the datasets have been transformed using end-to-end encryption before data release. All relevant medical diagnoses in this study were recorded with the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Given the anonymization of all personal identifiers in the database, the Institutional Review Board of Buddhist Dalin Tzu Chi Hospital confirmed that this study met the exemption criteria for full review (No. B10802014). This study was also conducted in accordance with the guidelines of the Helsinki Declaration.

Explication of study cohort

To be included in this survey, the study cohort was identified as adults aged 20 to 70 years with new-onset T2D episodes between 2000 and 2010. To reduce misclassification bias, patients were classified as having T2D if they had at least one hospital admission or three or more outpatient visits within 365 calendar days (ICD-9-CM code 250). The first prescription date or hospital admission date was considered the starting point for the time at risk with T2D. In addition, we excluded individuals who were followed for less than 1 year or had incomplete data (n = 446). Additionally, individuals diagnosed with T2D after developing periodontitis were removed to ensure the proper temporal direction between T2D and incident periodontitis (n = 19289). Based on this series of filters, a total of 40706 new-onset T2D individuals were included in this investigation (Figure 1).

Figure 1 Flowchart showing the method of selecting and following study subjects. T2D: Type 2 diabetes.

Clarifications of periodontitis and its ambulatory care utilization

In this investigation, individuals were identified as having periodontitis if they received at least three outpatient clinic visits in 1 year or one hospitalization during the study period, with ICD-9 codes 523.3, 523.4, 523.5, and 523.8. All of the aforementioned indicators were limited to those occurring after T2D onset. Regarding another outcome of interest, periodontitis-related ambulatory care utilization, this referred to the number of ambulatory visits and related costs in which participants sought dental consultation services associated with the specified ICD-9-CM codes. Relevant records occurring from the index date to the end of follow-up were retrieved and summarized. Additionally, ambulatory care costs were converted from New Taiwan Dollars to USD using a fixed 2013 exchange rate of USD 1.0 = New Taiwan Dollar 29.71.

Measure of medicinal herbs use

Under the NHI program, only certified Chinese medicine physicians are authorized to provide medicinal herb treatments. Following the previously used definition, individuals receiving routine care plus medicinal herb treatment for diabetes for more than 30 days were considered users of medicinal herbs[17], and the remaining subjects were designated as nonusers. Based on this classification, a total of 9728 enrollees were categorized as medicinal herb users in this study. Each herb user was then randomly matched to one nonuser with the closest propensity score, which ranged between -0.1 and +0.1[18]. The propensity score was calculated using logistic regression that included covariates potentially influencing the likelihood of using medicinal herbs, such as age, gender, monthly income, residential area, and comorbidities[19]. In this study, for those receiving medicinal herbs, the time period between the date of T2D diagnosis and the first date of medicinal herbs exposure after T2D represented the immortal time, which could lead to an overestimation of the intervention’s impact. To reduce this bias, the person-years (PY) were calculated starting from the initiation of medicinal herbs use to correct for immortal time for those receiving medicinal herbs treatment[20]. Therefore, the index date of the follow-up period for the nonusers was assigned to the date of the first T2D diagnosis, while the index date of the follow-up period for users of medicinal herbs was assigned to the first date of taking medicinal herbs. The follow-up period was determined by calculating the interval from the index date to the earliest of the following endpoints: Periodontitis onset, withdrawal from insurance, or December 31, 2013.

Identification of covariates

Based on former research[19,21], the covariates analyzed included several individual-level factors, such as gender, age, individual monthly salary, urbanization level in residential areas, and previous medical comorbidities. The premium payment category was employed as a substitute for average monthly salary in New Taiwan dollars in which it was divided into three ranks that contained lower quartile (≤ 35000), median (35001-70000), and upper quartile (≥ 70001). After complying with the criteria established by Liu and colleagues, the urbanization levels of residential districts for study participants were subdivided into three groups in which it covered urban (levels 1-2), suburban (levels 3-4), and rural (levels 5-7) areas[22]. Burden of pre-existing comorbidities was evaluated using the Charlson-Deyo comorbidity index. This is a validated scoring system incorporating 17 weighted comorbid conditions, ranging from 1 to 6, with higher scores indicating a more severe degree of comorbidity burden[23]. A comorbid condition was included if it was recorded 1 year preceding the cohort entry date.

Statistical analysis

All statistical analyses were carried out using SAS Version 9.3 (SAS Institute Inc., Cary, NC, United States). Results for continuous variables with normal distributions were described using mean ± SD while outcomes for discrete variables were presented as n (%). Distributions of sociodemographic characteristics and comorbidities between the two groups were compared using the independent two-sample t-test for continuous variables and χ² tests for categorical variables. For comparing ambulatory medical services, including frequency and cost of care due to periodontitis, the 2-sample nonparametric Mann-Whitney U test was used. Subsequently, the impact of medicinal herb involvement on periodontitis risk was assessed using Cox proportional hazards regression, adjusting for individual characteristics at baseline, and reported as hazard ratios (HRs) with 95% confidence intervals (95%CIs). To explore the association between medicinal herb use and subsequent periodontitis in greater detail, users of medicinal herbs were subdivided into three groups based on total days of use: 31-365 days, 366-730 days, and more than 730 days. The Kaplan-Meier method and log-rank test were applied to estimate event-free survival rates and to examine differences in periodontitis risk across the four groups. A log[-log(survival)] vs log of survival time plot was inspected to verify the proportional hazards assumption. A statistically significant would generate on the condition that P value is less than 0.05.

RESULTS

After the matching procedure, those with and without receiving combined medicinal herbs contributed data on 9728 individuals each. The corresponding sociodemographic and clinical characteristics are shown in Table 1. Among all recruited participants, the mean age was 54.3 ± 10.4 years, and nearly 60% were female. The majority had a median monthly income level (57.9%) and tended to reside in more urbanized areas (70.2%). Pertinent characteristics, including age, sex, monthly income, residential area, and comorbidities, did not reach statistical significance.

Table 1 Demographic data and selected comorbidities of the study subjects.

Variables	All participants	Nonusers of medicinal herbs, n = 9728	Users of medicinal herbs, n = 9728	P value
Age (year)	54.3 ± 10.4	54.3 ± 10.5	54.3 ± 10.4	0.91
≤ 50	6622 (34.0)	3305 (34.0)	3317 (34.1)	0.86
> 50	12834 (66.0)	6423 (66.0)	6411 (65.9)
Gender				0.97
Female	10893 (56.0)	5445 (56.0)	5448 (56.0)
Male	8563 (44.0)	4283 (44.0)	4280 (44.0)
Monthly income				0.40
Low	7473 (38.4)	3765 (38.7)	3708 (38.1)
Median	11260 (57.9)	5617 (57.7)	5643 (58.0)
High	723 (3.7)	346 (3.6)	377 (3.9)
Residential area				0.12
Urban	10461 (53.8)	5302 (54.5)	5159 (53.0)
Suburban	397 (16.4)	1569 (16.1)	1628 (16.7)
Rural	5798 (29.8)	2857 (29.4)	2941 (30.2)
CCI	3.92 (6.1)	3.91 (5.9)	3.94 (6.2)	0.35

Data were showed as n (%) or mean ± SD. CCI: Charlson-Deyo comorbidity index.

Within the study period, a total of 9297 first episodes of periodontitis occurred during an observation period of 130707.6 PY among whole enrollees. From the multivariate analysis, we observed that T2D individuals receiving polytherapy had a significantly lower incidence rate of periodontitis at 64.41 per 1000 PY, compared with 78.16 per 1000 PY for those receiving only conventional care, with an adjusted HR of 0.79 (95%CI: 0.76-0.83; Table 2). Notably, the protective effect of medicinal herbs became especially clear when participants received them for more than two years (adjusted HR = 0.48; 95%CI: 0.41-0.57). Kaplan-Meier analysis of survival by days of medicinal herb use revealed a significant difference in the survival rate free from periodontitis across the four groups (P < 0.001; Figure 2). Regarding ambulatory care consumption between treated and untreated groups, the nonusers incurred substantially higher numbers of periodontitis-related ambulatory visits across all follow-up intervals. Importantly, among nonusers of medicinal herbs, the cost per ambulatory care episode due to periodontitis after T2D onset continuously rose up (Table 3). The differences between the two groups widened progressively over the duration of periodontitis.

Figure 2 Kaplan-Meier curves plotting cumulative incidence of periodontitis across four groups (Log-rank test, P < 0.001). PY: Person-years.

Table 2 Risk of periodontitis for type 2 diabetes subjects with and without adding medicinal herbs.

Participants	Event	PY	Incidence	Crude HR (95%CI)	Adjusted HR1 (95%CI)
Nonusers of medicinal herbs	4991	63852.56	78.16	1	1
Users of medicinal herbs	4306	66855.04	64.41	0.80 (0.75-0.84)	0.79 (0.76-0.83)
Group 1 (use for 31-365 days)	3823	56306.79	67.89	0.86 (0.81-0.90)	0.84 (0.80-0.87)
Group 2 (use for 366-730 days)	340	6800.35	50.01	0.64 (0.56-0.70)	0.60 (0.54-0.67)
Group 3 (use more than 730 days)	143	3747.90	38.15	0.49 (0.41-0.57)	0.48 (0.41-0.57)

¹Model adjusted for age, gender, monthly income, residential area and Charlson-Deyo comorbidity index.

PY: Person-years; HR: Hazard ratio; 95%CI: 95% confidence interval.

Table 3 Comparisons of frequency and costs of periodontitis-related ambulatory care between two groups from the index date to the end of follow-up.

	Users of medicinal herbs	Nonusers of medicinal herbs	P value
Within 1 year after periodontitis
Total visits of ambulatory care	10829	12602	< 0.001
Mean costs for per ambulatory care	55.36	60.66	< 0.001
1-3 years after periodontitis
Total visits of ambulatory care	15137	16810	< 0.001
Mean costs for per ambulatory care	51.92	70.33	< 0.001
3 years or more after periodontitis
Total visits of ambulatory care	19288	30846	< 0.001
Mean costs for per ambulatory care	50.56	107.30	< 0.001

Costs were transformed into USDs according to the exchange rate of 2013.

Multivariable stratified analysis showed that younger individuals with T2D benefited the most in preventing periodontitis. Similarly, the effect of medicinal herb therapy in reducing periodontitis incidence was more pronounced among females, with an adjusted HR of 0.70 (95%CI: 0.67-0.75; Table 4). The top ten prescribed herbal formulas for T2D treatment are shown in Table 4. Among them, Hai-Piao-Xiao, Dan-Shen, Chuan-Qi, Huang-Qi, Da-Huang, Shu-Jing-Huo-Xue-Tang, Shao-Yao-Gan-Cao-Tang, Ji-Sheng-Shen-Qi-Wan, and Xue-Fu-Zhu-Yu-Tang were associated with a reduced risk of periodontitis (Figure 3).

Figure 3  Risk of periodontitis in relation to the 10 most-used single-herb and multi-herb products among type 2 diabetes subjects.

Table 4 Incidence and periodontitis risk for type 2 diabetes patients with and without medicinal herbs use stratified by sex and age.

Variables	Nonusers of medicinal herbs			Users of medicinal herbs			Crude HR (95%CI)	Adjusted HR (95%CI)
	Case	PY	Incidence	Case	PY	Incidence
Sex
Female	2977	34644.4	85.93019	2431	38156.72	63.71	0.73 (0.69-0.77)	0.701 (0.67-0.75)
Male	2014	29208.16	68.95333	1875	28698.32	65.33	0.93 (0.87-0.98)	0.911 (0.86-0.96)
Age (year)
≤ 50	1946	19042.44	102.1928	1652	21676.83	76.21041	0.75 (0.69-0.79)	0.742 (0.69-0.78)
> 50	3045	44810.12	67.9534	2654	45178.21	58.74513	0.86 (0.79-0.88)	0.832 (0.79-0.87)

¹Model adjusted for age, urbanization level, monthly income, medication use and CCI.

²Model adjusted for sex, urbanization level, monthly income, medication use and CCI.

PY: Person-years; HR: Hazard ratio; 95%CI: 95% confidence interval.

DISCUSSION

Not only does periodontitis impair social interaction in individuals with T2D, but it also compromises their prognosis, as reflected by the increased risk of cardiorenal mortality. Faced with these serious consequences, oral health should be managed proactively alongside T2D treatment. Results of this study revealed that integrating medicinal herbs into routine diabetic care can significantly reduce risk of incident periodontitis. Specifically, we observed a 52% reduction in periodontitis risk among those receiving medicinal herbs for more than two years. Furthermore, if individuals with T2D develop periodontitis, the early addition of medicinal herbs to their diabetes care would markedly reduce periodontitis-related ambulatory service utilization. Although few head-to-head comparisons are available, the positive association between medicinal herb use and reduced periodontitis risk supports previous findings and strengthens the growing body of evidence on this issue[24]. We postulate that the potential of medicinal herbs may relate to phytochemicals that comprised the regulation of inflammation and promotion of bone mineral density, both critical in periodontitis development[15]. Additionally, the pronounced benefit in females may be linked to reduced hormone release, particularly estrogen, which may dampen inflammatory mediators such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) RNA expression[25], thereby enhancing the therapeutic efficacy of herbal agents.

Additionally, from the commonly prescribed multi-herb formulas, we found that taking Shu-Jing-Huo-Xue-Tang or Shao-Yao-Gan-Cao-Tang was associated with a significantly lower subsequent risk of periodontitis. Consistent with prior findings, Shu-Jing-Huo-Xue-Tang is frequently used to address diabetic complications, including neuropathy and cardiovascular manifestations[26,27]. While Shao-Yao-Gan-Cao-Tang is not a primary antidiabetic agent, earlier reports suggest it may support muscle relaxation and contribute to blood sugar regulation[28]. Notably, both herbs have been shown to downregulate plasma cytokine levels associated with aberrant inflammatory responses by suppressing the TLR4/NF-κB pathway[29,30]. Dysregulated activation of this inflammasome pathway may accelerate pyroptosis in periodontal tissues and promote overproduction of inflammatory mediators, both of which are recognized contributors to periodontitis development[15].

Likewise, we identified that some commonly prescribed herbs may abate the likelihood of periodontitis, such as Ji-Sheng-Shen-Qi-Wan and Xue-Fu-Zhu-Yu-Tang. Compared with untreated controls, an earlier report showed that ovariectomized mice fed Ji-Sheng-Shen-Qi-Wan for 8 weeks experienced less bone mass loss and microarchitectural deterioration via inhibition of the NLRP3/caspase-1 pathway[14]. This signaling axis is known to play a critical role in maintaining bone homeostasis[31]. Regarding Xue-Fu-Zhu-Yu-Tang, its anti-inflammatory action has been confirmed in modern pharmacological experiment. For example, a murine model treated with purified Xue-Fu-Zhu-Yu-Tang exhibited significantly reduced plasma levels of arachidonic acid, TNF-α, and IL-1β via inhibition of the PI3K-AKT-mTOR pathway[32], which in turn suppressed NLRP3 inflammasome activation and enhanced osteoblast proliferation and differentiation[33]. The osteogenic promotion via regulation of inflammatory damage is a key mechanism by which these polyherbal formulas combat periodontitis in the studied population.

Additionally, this study suggests that certain single herbs containing Huang-Qi and Hai- Piao-Xiao may offer potential for the prevention of periodontitis. In a previous study, Huang-Qi was shown to dose-dependently modulate serum levels of inflammatory cytokines by regulating inflammation-associated pathways such as Ras-PI3K-Akt-HIF-1α and NF-κB[34]. Furthermore, baicalin, a flavonoid compound derived from Huang-Qin, may significantly activate alkaline phosphatase via the mammalian target of rapamycin complex 1 pathway, thereby promoting osteoblast differentiation markers and possibly reducing subsequent risk of periodontitis[35]. Similarly, a recent randomized controlled trial by Neubrech et al[36] reported that chitosan, a principal constituent of Hai-Piao-Xiao, can effectively enhance peripheral sensory nerve regeneration through its antioxidant properties, which in turn supports matrix protein synthesis during osteoblast differentiation[8,15].

Of the commonly prescribed single-herb products to treat T2D, we observed that Da-Huang, Dan-Shen, and Chuan-Qi were also significantly associated with a reduced risk of periodontitis. After recruiting 53 patients undergoing free gingival graft treatment, the scholars found that emodin, a major constituent of Da-Huang, not only markedly ameliorated postoperative pain perception but also exerted anti-inflammatory activity by inhibiting the expression of iNOS and Cox-2 mRNA[37], both of which are known to play indispensable roles in gingival inflammation and tissue destruction related to periodontitis[8,38]. Regarding the therapeutic benefits of Dan-Shen and Chuan-Qi, the benefits may be relevant to their respective extracts, such as salvianolic acid from Dan-Shen and saponins from Chuan-Qi. These compounds reportedly exhibit antibacterial properties due to their intrinsic alkaline nature[39,40]. Maintenance of the oral acid-alkaline balance can significantly prevent the formation of plaque and calculus in saliva, thereby reducing the subsequent risk of periodontitis to some extent. The findings presented here may further support those of other studies in the literature, which emphasize that incorporating medicinal herbs into existing therapeutic agents may be a viable strategy for effectively managing periodontal health in addition to glycemic control.

Despite its important public health implications, this study has some questions that remain unresolved. First, we may have encountered errors in the coding process while using secondary healthcare databases. To mitigate this limitation, we included only individuals with new-onset T2D or periodontitis and required at least three outpatient visits with consistent diagnoses or at least one inpatient admission. Nevertheless, because the coding strategy and data completeness were comparable between two groups, we assume the nondifferential misclassification is likely to produce bias towards the null. Second, laboratory and environmental factors influencing periodontitis risk, especially dietary habits and lifestyle, were not captured in this dataset. Yet, this underscores the rationale for using propensity score matching herein. In this work, the applications of propensity score matching approach together with the multivariate analyses should enable two groups to be balanced in terms of potential confounders to ensure comparability during data analyses. Future explorations incorporating these variables via well-designed randomized controlled trials are needed to validate the associations demonstrated in our study. Lastly, despite the evident benefit of medicinal herbs in lowering the risk of periodontitis, it must be acknowledged that participants were not randomly assigned to exposure groups at baseline. Therefore, a larger randomized cohort study of individuals with diabetes is necessary to confirm these findings and to elucidate the mechanisms by which medicinal plants may modulate the progression of periodontal disorders.

CONCLUSION

Considering that periodontitis is a common and frequently occurring condition following T2D onset and may triple cardiorenal mortality in individuals with diabetes, proactive measures should be taken to address these complications. Findings from this study are clinically relevant, as they support the notion that the addition of herbal products may reduce the likelihood of complications associated with T2D, particularly periodontitis. A pronounced effect of medicinal herbs against periodontitis development was observed when participants received medicinal herbs for over two years. Moreover, the early integration of medicinal herbs into conventional care significantly decreased subsequent use of periodontitis-related ambulatory services. In the long term, based on the principle that an ounce of prevention is worth a pound of care, healthcare professionals should periodically monitor the oral health of individuals with T2D. Meanwhile, patients with diabetes should be promptly informed and encouraged to remain vigilant for early signs and symptoms of periodontitis, enabling them to optimize health prevention and adhere to diabetes self-management. Most importantly, throughout the diabetic care process, integrating targeted preventive strategy that combine alternative and complementary approaches into routine care should be considered a top priority for managing both oral health and glycemic control.

ACKNOWLEDGEMENT

We thank the practical consultation from Dr. Yen Chia-Chou.