2011 John Wiley & Sons A/S

Periodontology 2000, Vol. 56, 2011, 258268

Printed in Singapore. All rights reserved

PERIODONTOLOGY 2000

Relationship between
periodontal disease and diabetes
mellitus: an Asian perspective
T A R A B. T A I Y E B -A L I , R E N U K A N T H P. C H E T A R A M A N &
R A T H N A D. V A I T H I L I N G A M

Physicians and dentists have restricted themselves

to their own respective fields in the past, only
treating diseases that are relevant to their own
fields of specialization. However, recent findings
indicate that oral health may influence systemic
health, and that this may be a bi-directional relationship for some conditions. This is particularly
true for the relationship between periodontal disease and diabetes mellitus. The inter-relationship
between periodontal disease and diabetes mellitus
provides an example of a cyclical association,
whereby a systemic disease predisposes the individual to oral infections, and, once the oral infection is established, it exacerbates the systemic
disease. There are also associations between periodontal disease and systemic conditions such as
cardiovascular problems, pulmonary conditions,
osteoporosis, obesity, pancreatic cancer and Alzheimers disease. Hence, emphasis should now be
placed on treating periodontal and other chronic
dental diseases as a means of ameliorating systemic
diseases.

Diabetes mellitus
Diabetes mellitus comprises a clinically and genetically heterogeneous group of metabolic disorders
manifested by abnormally high levels of glucose in
the blood (56). This abnormally high level of glucose
in the blood is brought about by insulin deficiency
caused by pancreatic b-cell dysfunction, insulin
resistance in the liver or muscle tissue, or a combination of both. It is known that chronic hyperglycemia leads to long-term damage of various organs

258

such as the heart, eyes, kidneys, nerves and vascular

system.
The American Diabetes Association released a new
classification and diagnostic criteria for diabetes
mellitus in 1997, and this was modified in 2003 (4).
The new classification divides this metabolic disorder
into four general categories: type 1, type 2, idiopathic
and gestational diabetes mellitus.

Type 1 diabetes mellitus

Type 1 diabetes mellitus results from cellular-mediated immune b-cell destruction, frequently leading to
total loss of insulin secretion. Type 1 diabetes
mellitus is usually reported in children and young
adolescents.

Gestational diabetes mellitus

Gestational diabetes mellitus is defined as glucose
intolerance of various degrees that is first detected
during pregnancy. Gestational diabetes mellitus
is detected by screening of pregnant women for
clinical risk factors, and, among at-risk women,
testing for abnormal glucose tolerance, which is
usually, but not invariably, mild and asymptomatic.
Gestational diabetes mellitus appears to result from
the same broad spectrum of physiological and
genetic abnormalities that characterize diabetes
outside of pregnancy. Indeed, women with gestational diabetes mellitus are at high risk of developing
diabetes when they are not pregnant. Thus gestational diabetes mellitus provides a unique opportunity to study the early pathogenesis of diabetes and to
develop interventions to prevent the disease (11).

Periodontal disease and diabetes

Idiopathic diabetes
Some forms of type 1 diabetes have no known etiology. These patients have no evidence of autoimmunity but present with permanent insulinopenia and
are prone to ketoacidosis. Such patients represent a
minority of patients with type 1 diabetes, and the
majority of these patients are of African or Asian
ancestry (56). This form of diabetes is strongly
inherited, lacks immunological evidence of b-cell
autoimmunity, and is not human leukocyte antigenassociated (56). Affected patients may or may not
require insulin replacement therapy.

Type 2 diabetes mellitus

Type 2 diabetes mellitus, previously defined as noninsulin-dependent diabetes, results from insulin
resistance and to a certain extent altered insulin
production. It is associated with microvascular (i.e.
retinal, renal, possibly neuropathic), macrovascular
(i.e. coronary, peripheral vascular) and neuropathic
(i.e. autonomic, peripheral) complications.
Hyperglycemia results from a lack of endogenous
insulin, which is either absolute, as in type 1 diabetes
mellitus, or relative, as in type 2 diabetes mellitus.
Relative insulin deficiency usually occurs because of
resistance to the actions of insulin in muscle, fat and
the liver, and an inadequate response by the pancreatic b-cells.
Insulin resistance, which has been attributed
to elevated levels of free fatty acids in plasma, leads
to decreased glucose transport in muscle, elevated
hepatic glucose production, and increased breakdown of fat (10). The genetics of type 2 diabetes are
complex and not completely understood, but presumably this disease is related to multiple genes
(with the exception of maturity-onset diabetes of the
young).
The evidence supports the existence of inherited
components for pancreatic b-cell failure and insulin
resistance. Considerable debate exists regarding the
primary defect in type 2 diabetes mellitus. Most
patients have insulin resistance and some degree of
insulin deficiency. However, insulin resistance per se
is not the absolute indicator for type 2 diabetes
mellitus, because many people with insulin resistance (particularly those who are obese) do not
develop glucose intolerance. Therefore, insulin deficiency is necessary for the development of hyperglycemia. Insulin concentrations may be high but
inappropriately low for the level of glycemia (45).
Presumably, the defects of type 2 diabetes mellitus

occur when a susceptible individual lives a diabetogenic lifestyle (i.e. excessive caloric intake, inadequate caloric expenditure, obesity). The body mass
index at which excess weight increases the risk for
diabetes varies with different racial groups. For
example, compared with persons of European
ancestry, persons of Asian ancestry are at an increased risk for diabetes at lower levels of overweight
(30, 98) and at a younger age (33).
Type 2 diabetes is quickly becoming a pandemic,
and it has been predicted that it will affect more than
300 million people by 2025 (68). The United Nations
has estimated that the number of people globally
who are affected by diabetes is 246 million, and
approximately half of those are in India, China, Nepal
and other Asian countries (33). The prevalence of
diabetes mellitus has increased worldwide, particularly in the Asia-Pacific region since 1995 (13, 37), and
it is believed that by the year 2025 about 60% of the
worlds diabetic population will come from Asia (37).
In China, the prevalence of diabetes increased from
1% in 1980 to 5.5% in 2001 (27). Nearly 10% of
Chinese adults residing in affluent Hong Kong and
Taiwan have diabetes (35). Approximately two-thirds
of the adult Chinese population in Mainland China
and half of those in Hong Kong and Taiwan remain
undiagnosed diabetics (96).
In India, the diabetes prevalence in adults has
increased from 3% in the 1970s to 12% in 2000 (70).
Epidemiological studies in India have shown that the
prevalence of diabetes is high and is increasing,
especially in the urban population, i.e. it increased
from 5% in 1986 to 8.2% in 1992 to 11.4% in 1997
among adults in urban areas (1, 69, 71, 72).
In Singapore, Indians were found to have the
highest prevalence of diabetes (12.8%), followed by
Malays (11.3%) and Chinese (8.4%) in a 1998 study
(44). The results of a population-based study in
Singapore showed that the age- and sex-standardized prevalence of diabetes mellitus among Malay
adults aged 4080 years was 18.4%. This finding is
similar to the age group-specific prevalence reported
in the 2004 National Health Survey in Singapore
(58). However, in this survey, the prevalence of
diabetes mellitus was highest in Indians (15%), followed by Malays (11%) and Chinese (7%). Malays in
Singapore had the highest prevalence of obesity and
total cholesterol levels. Genetic predisposition and
obesity have been implicated as possible reasons for
the increased prevalence of diabetes among Asian
Indians (76).
The Nepal Diabetes Association (84) reports that
among people aged 20 years and older living in

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Taiyeb-Ali et al.

urban areas, 15% are affected by this condition, and

this number rose to 19% among people aged
40 years and older in urban areas. In Mauritius,
13% of the population have been found to have
type 2 diabetes mellitus (60). In the United Arab
Emirates, 25% of the population is affected by diabetes, the second highest prevalence of diabetes
worldwide.
Approximately 11% of Malays living in Malaysia
have diabetes (100). In Malaysia, there are nearly 1.2
million people who have diabetes, of whom 98%
have type 2 diabetes (7). In an epidemiological survey performed in a semi-rural community in
Malaysia in 1993 on 1417 subjects, the prevalence of
diabetes was high at 10.7%, with a further 10%
having a measured fasting plasma glucose level
7 mmol l. This is consistent with the National
Health & Morbidity Survey of Malaysia 2006 (101),
in which the diabetes prevalence in adults was reported to be 14.9%. This is in contrast to developed
countries, both the USA and Europe, in which
prevalence of diabetes is much lower at between 6
and 8% (18).
Diabetes has far-reaching socio-economic implications and is a major public health burden due to
the disease per se and the complications that
accompany it. The considerable heterogeneity in
ethnicity, cultures and economic development in
Asia, all of which could affect both diabetic and
periodontal conditions, need to be considered.
This metabolic syndrome is now viewed as an
inflammatory condition, and its development is
preceded by low-grade systemic inflammation (20).
As such, elevated plasma concentrations of proinflammatory mediators markers such as C-reactive
proteins, cytokines (interleukin-1b, interleukin-6,
tumor necrosis factor a) and prostanoids (prostaglandin E2) are seen in patients suffering from type 2
diabetes mellitus (8).
An important source of cytokines in diabetes is
adipose tissue. Adipose tissue was previously considered as a passive store of lipids, but now it is clear
that fat cells are active endocrine organs secreting
hormones and inflammatory mediators. Therefore,
obesity is the strongest risk factor for type 2 diabetes
(31), which, in turn, is a risk factor for periodontal
disease (48).
Although other common risk factors for diabetes
mellitus and periodontal disease, such as smoking,
have been suggested, the question remains whether
periodontal disease could be a possible risk factor for
diabetes mellitus in Asians given the high periodontal
disease prevalence in this region.

260

Periodontal disease
Periodontal disease is a chronic inflammatory disease
characterized by inflamed gingiva, bleeding on
probing, resorption of alveolar bone and attachment
loss between the tooth and its surrounding alveolar
bone. A typical feature of periodontitis is an imbalance in the anabolic and catabolic processes of the
hard tissue, ultimately resulting in bone loss. The
increased secretion of inflammatory mediators leads
to disruption of the anabolic and catabolic processes,
starting with modifications in the morphology of the
periodontal tissues.
An ecological niche for bacteria exists at the junction between the gingiva and the teeth, which
develops from a healthy gingival sulcus to a periodontal pocket. A delicate equilibrium between the
microbial ecology and the host response exists in this
niche (65). An area of ulceration of the pocket epithelium and inflammation alongside healing processes results in local tissue destruction of the gingival and periodontal tissues when this fine balance is
disturbed, with possible systemic dissemination of
microbial products and host inflammatory mediators.
The inflammatory response in the periodontal tissues in response to challenge by dental biofilm is
complex and involves networks of cytokines functioning in synergy. The inflammatory response is
characterized by localized production of various
inflammatory markers and enzymes, such as
C-reactive proteins, cytokines (interleukin-1b, interleukin-6, tumor necrosis factor a), prostanoids
(prostaglandin E2) and matrix metalloproteinases.
These increased secretions of inflammatory cytokines
contribute to bone loss in periodontitis.
The balance between the protective host factors
and microbial challenge is greatly influenced by
environmental and genetic factors that have an
impact on the immuno-inflammatory response of the
host. Alterations in immunologically active molecules
as a result of diabetes may alter the levels of cytokines
in the periodontium, which accelerates progression
of the disease. This is the scientific basis for the
increased susceptibility to periodontal disease seen
in diabetics.
There is a generally held view that Asians are particularly susceptible to periodontitis (15). This opinion appears to have originated from epidemiological
studies that compared immigrant Asians and Caucasians from industrialized nations. A classic longitudinal study comparing Norwegian males and Sri
Lankan Tamil males showed far worse periodontal

Periodontal disease and diabetes

conditions in the Asian males (4951). In 2003, it was

reported that the Thai population may have more
widespread and severe periodontal destruction than
other Asian populations (6).

Diabetes mellitus as a risk factor

for periodontitis
Numerous risk factors for periodontal disease have
been identified, and diabetes mellitus is a widely
accepted major factor, particularly in the Asian
region (53, 66). Diabetes has been found to be an
important host risk factor in periodontal diseases in
large epidemiological studies (4951). Landmark
studies relating periodontitis to type 2 diabetes
mellitus such as the Pima Indian study showed
increased prevalence and incidence of periodontal
disease in those individuals who also had type 2
diabetes compared to those who did not (61). Data
obtained from several studies also strongly suggest
diabetes as a risk factor for gingivitis and periodontitis (55). Evidence suggests that periodontal changes
are the first clinical manifestation of diabetes (42).
Patients with diabetes exhibited greater periodontal breakdown in response to dental biofilm; however, this depended on the degree of glycemic control
(8, 5, 8). The highest levels of gingivitis were seen in
diabetic patients with poor glycemic control (54).
Clinical and epidemiological studies have reported a
higher prevalence and increased severity of periodontal disease in diabetic patients compared
with non-diabetic controls (12, 14, 77). Studies have
shown that diabetes carries a threefold increased risk
of periodontitis compared to non-diabetic individuals (49, 83). Alveolar bone loss is enhanced in these
individuals, resulting in a more persistent inflammatory response in diabetics. This leads to greater
attachment loss and impaired formation of new bone
(47). In addition, Loe (48) described periodontitis as
the 6th complication of diabetes, together with retinopathy, nephropathy, neuropathy, macrovascular
diseases and altered wound healing.
Arrieta-Blanco et al. (5) reported a higher gingivitis
index and gingival recession in diabetic patients compared to controls. Similarly, Lu & Yang (52) compared
72 type 2 diabetes patients with 92 non-diabetics and
reported a higher gingival index and attachment loss
which was positively associated with glycated haemoglobin or haemoglobin A1c (HbA1c) levels in diabetic patients. Multiple regression analysis revealed
that the main factors affecting the gingival index were
the presence or absence in diabetic patients of HbA1c

values 10%, with those who had higher mean gingival index values having higher HbA1c values.
Researchers in Singapore reviewed epidemiological, clinical and laboratory studies, and showed that
the severity of periodontal breakdown is related to
both direct and indirect effects of glycemic control.
However, it is not clear whether there is a true
bi-directional relationship between glycemic control
and periodontal destruction (89). Recently, Lim et al.
(46) evaluated the relationship between markers of
metabolic control and inflammation and the severity
of periodontal disease in 181 patients with type 1 or 2
diabetes mellitus. They reported positive correlations
between HbA1c and the percentage of sites with
bleeding on probing and probing depths, providing
further evidence for the importance of glycemic
control.
In studies in Taiwan, conflicting results were found.
No difference was noted in the periodontal disease
status of 105 non-insulin dependent diabetes mellitus
patients and 141 non-diabetic controls in a study of
adult Taiwanese patients (99). However, the prevalence of four pathogens (Porphyromonas gingivalis,
Eikenella corrodens, Treponema denticola and Candida albicans) was significantly higher in diseased sites
than healthy sites in both groups (99). There was a
significant difference in probing attachment levels
between the non-insulin dependent diabetic group
and matched controls (96), and type 2 diabetes mellitus was positively associated with greater risk for
periodontal disease, with a 10% higher prevalence in
subjects with type 2 diabetes than those without (95).

Obesity as a risk factor for periodontitis

The link between periodontal disease and obesity has
been suggested to be attributed to (i) the hyperinflammatory state, (ii) the aberrant lipid metabolism
prevalent in obesity, and (iii) the pathway of insulin
resistance (63, 80). Collectively, these may result in
enhanced breakdown of the periodontal tissue support. A number of recent studies indicate a positive
association between obesity, defined as body mass
index (BMI) 30, and periodontitis (2, 59, 79, 97).
Subjects with a body mass index > 30 had a higher
community periodontal index, and the situation was
made worse by the presence of more components of
the metabolic syndrome (39).
Overweight subjects in the upper quartile of the
insulin resistance index were 1.5 times more likely to
have periodontitis as compared to those with a high
BMI but a low insulin resistance index. Al-Zahrani
et al. (2) reported a significant association between

261

Taiyeb-Ali et al.

both BMI and waisthip ratio and periodontitis in

younger adults, but no association in middle-aged or
older adults. In Caucasian subjects aged 18 years and
above, it was reported that BMI, waisthip ratio,
visceral fat and fat-free mass are associated with
periodontitis, after adjusting for age, gender, history
of diabetes, current smoking status and socio-economic status (2). In a subject sample of 643 apparently healthy Japanese adults, Saito et al. (79)
reported that waisthip ratio, BMI and body fat were
significant indicators for periodontitis after adjustment for other known risk factors.

Role of diabetes mellitus in periodontal

disease
Periodontal inflammation is initiated by gram-negative bacterial infection of the periodontal pocket (85),
whereas diabetic inflammatory complications are
mainly a result of hyperglycemia. Both share common pathogenic processes and both can be thought
of as up-regulated or mal-adapted responses of the
immune system to environmental stressors acting on
the host (68).
The effects of hyperglycemia on oral health can be
ascribed to three pathological mechanisms (75).
First, hyperglycemia leads to increased blood glucose
levels, and oral fluids such as saliva and gingival
crevicular fluid reflect the elevated blood glucose
levels. This correlation may influence the microbial
flora in the oral cavity, both in attached biofilm and
planktonic biomass. In particular, the growth of
anaerobic bacterial strains at the base of periodontal
pockets may be favored at the expense of other
bacterial species. In this context, hyperglycemia may
induce and accelerate the inflammatory processes in
the mouth. Second, hyperglycemia also increases the
concentration of advanced glycation end-products.
The elevated levels of blood glucose lead to pathological biochemical processes such as glycation of
protein-like collagens or lipids and non-enzymatic
oxidative destruction. Advanced glycation end-products can directly affect normal protein function, or
indirectly act by reacting with receptors on the cell
membrane of a variety of cells. These glycated
products have the potential to create molecular
complexes, reducing the solubility of the target
protein-like collagens. They alter the functional
properties of several important matrix molecules
such as type 1 collagen and laminin. Interactions
between advanced glycation end-products and their
receptors interactions mediate long-term effects such
as expression of cytokines and growth factors by

262

macrophages and mesangial cells. Thus, inflammatory responses induced by advanced glycation endproducts contribute to systemic degradation of connective tissue in diabetic patients and consequently
periodontal tissues (86). Consistent with this concept,
blockade of receptors for the advanced glycation endproducts through systemic administration of soluble
receptors for advanced glycation end-products
(sRAGE) in a murine model of diabetic periodontal
disease diminished alveolar bone loss, probably by
blocking the activation of innate immunity and reducing the effects of oxidative stress (41). This suggests the possibility that blocking receptors for the
advanced glycation end-products may be an effective
approach in treating periodontal disease as a complication of diabetes. Third, matrix metalloproteinases are involved in a number of physiological events,
and are the major players in collagen breakdown
during periodontal tissue destruction. Diabetes
mellitus has been associated with altered collagen
metabolism and increases the response of the periodontal tissue to pathogenic microorganisms, thereby increasing the severity of periodontal disease. An
increased concentration of matrix metalloproteinases
8 and 9 in the gingival tissue of diabetic chronic
periodontitis patients suggests that expression of
these matrix metalloproteinases contributes to failure
of the healing process in the diabetic condition.
Treatment directed towards the inhibition of matrix
metalloproteinases could lead to improved healing
rates in chronic periodontitis patients (86).

Periodontitis as a risk factor for

diabetes mellitus
A recent hypothesis has suggested that subclinical
inflammation is linked to insulin resistance (3). The
triggers of inflammation are many, and potentially
include oral infection. These oral infections result
in a cascade of events that include increased cytokine production, activation of acute-phase protein
synthesis and consequent insulin resistance, producing pathogenic changes resulting in type 2 diabetes (3).
Due to the dynamic nature of the inflamed periodontium, the tissue may serve as an endocrine-like
source of inflammatory mediators (24, 64). Chronic
periodontal infection leads to an increase in serum
tumor necrosis factor a, interleukin-1, interleukin-6
and C-reactive proteins (24). The increase in these
cytokines may increase insulin resistance by interfering with glucose and lipid metabolism (24) and

Periodontal disease and diabetes

antagonizing insulin action (67). The increased insulin

resistance will ultimately cause an increase in the risk
for type 2 diabetes. In studies of links between periodontal disease and cardiovascular disease, C-reactive
proteins and interleukin-6 have been shown to be the
implicated inflammatory markers and mediators due
to their possible biological mechanisms (36). Some
studies have suggested that possible links between
cardiovascular disease and periodontal disease include direct bacterial effects on platelets and host
cells, systemically or locally induced inflammatory
mediators, and an autoimmune response (19, 22).
These links seem biologically plausible because the
DNA of P. gingivalis has been detected in atherosclerotic plaques (28). Both C-reactive proteins and
interleukin-6, together with interleukin-1, fibrinogen
and tumor necrosis factor a, are involved in
atherothrombogenesis (82), as well as periodontal
tissue destruction. Periodontitis and diabetes mellitus
could also potentially share similar features of
inflammation, with C-reactive proteins, interleukin-6
and other inflammatory mediators being common
denominators. Furthermore, a doseresponse relationship was seen between the severity of periodontal
disease and the circulating tumor necrosis factor
a level, which is closely linked with insulin resistance
(57). This implies that periodontal disease may play
a significant role in the occurrence of insulin
resistance.
In periodontal disease, reactive oxygen species,
products of normal cellular metabolism, are produced to excess. When stimulated by bacterial
pathogens, host cells release pro-inflammatory
cytokines (e.g. interleukin-1a, interleukin-1b and tumor necrosis factor a) as part of the immune
response (82). These cytokines recruit and stimulate
polymorphonuclear leukocytes, which in turn produce proteolytic enzymes (such as elastase) and
reactive oxygen species. The imbalance between
production of reactive oxygen species and antioxidant defense induces oxidative stress. The formation
of superoxides in turn mediates activation of the
polyol pathway, the hexosamine pathway, protein
kinase C and the formation of advanced glycation
end-products (73). Inflammatory responses induced
by advanced glycation end-products may subsequently contribute to systemic degradation of connective tissue in diabetic patients (86), thus increasing the risk of diabetic complications.
Bluher et al. (9) found a significant increase in
plasma concentrations of interleukin-6 and C-reactive proteins and a significant decrease in adiponectin and interleukin-10 in parallel with the impairment

of glucose tolerance. In a similar study, type 2

diabetes mellitus was found to be highest among
subjects with raised plasma levels of both interleukin-8 and C-reactive proteins or interleukin-8 and
interleukin-6 (94). These studies suggest that insulin
resistance is associated with an exaggerated acutephase response, and may precede the development of
type 2 diabetes.
In a 10-year cohort study, Saito et al. (78) found
that the increase in mean pocket depth was more
closely associated with the development of glucose
intolerance rather than past glucose tolerance status.
Other studies have suggested that the presence of
periodontal infection may be linked to poor metabolic control of diabetes (87). In their Pima Indian
study, Nelson et al. (61) showed that the extent of
periodontal infection was associated with glycemic
control (P < 0.001). It has been reported that diabetics with severe periodontal disease are six times more
likely to have poor glycemic control (91). Longitudinal observation studies have shown that infections of
periodontal origin have an adverse effect on glycemic
control (90), although not all patients showed an
improvement in glycemic control after periodontal
treatment. The evidence indicates that periodontitis
is a risk factor for poor glycemic control and the
development of other clinical complications of diabetes (42, 90).
In a recent study, Nibali et al. (62) investigated
whether periodontitis, as a chronic infection with
low-grade systemic inflammatory properties, might
be an etiological factor for and subsequently increase
the risk for diabetes and coronary heart disease.
Within the limitations of a casecontrol design, their
findings indicate that patients with untreated severe
periodontitis may be at increased risk of metabolic
syndrome and therefore diabetes and cardiovascular
disease. Metabolic syndrome is an obesity-related
condition characterized by obesity, dyslipidemia,
insulin resistance, high blood pressure and a proinflammatory and pro-thrombotic state (26). These
results provided further evidence for the inter-relationship between a cumulative burden of inflammation and diseases with multiple risk factors. Untreated
periodontal disease is a chronic inflammatory state
that leads to increased insulin resistance and reduced
glucose tolerance, and thereby increased risk of
diabetic complications, such as nephropathy and
cardiovascular disease. On the other hand, poorly
controlled diabetes increases the risk of periodontitis
and periodontal infection. Treatment of periodontal
disease can alter glycemic control, and early intervention and treatment of periodontitis may help to

263

Taiyeb-Ali et al.

prevent the long-term complications of diabetes,

thereby having an impact on mortality.
The Diabetes Control and Complications Trial (92)
provided evidence that improved control of blood
glucose reduces the risk of a number of long-term
complications of diabetes, especially retinopathy,
nephropathy and neuropathy. The major objective of
recent therapeutic approaches is to reduce the levels
of HbA1c, and maintain them at a low level. HbA1c
levels of 46% are normal, 6.17% indicates good
control, 7.18% indicates moderate control, and
levels > 8% indicate less favorable control (93).
In a small pilot study, Lalla et al. (40) investigated
the effects of periodontal treatment in patients with
diabetes. They discovered significant suppression of
serum C-reactive protein and soluble E-selectin, but
no change in plasma fibrinogen. The percentage of
mononuclear cells with pro-inflammatory properties
also significantly decreased. The authors concluded
that periodontal therapy may effect a reduction in the
production of tumor necrosis factor a and the number of circulating monocytes, which have implications in the inflammatory complications of diabetes,
especially atherosclerosis. This link between periodontitis and diabetes mellitus requires substantiation
also in Asian populations by well-designed controlled
trials.

Effects of periodontal therapy in patients

with diabetes
Intervention trials have assessed the potential effects
of periodontal therapy on glycemic control in subjects with diabetes. Rodriguez et al. (74) and Stewart
et al. (88) found a marked improvement in glycemic
control in type 2 diabetic patients following periodontal therapy.
Researchers have hypothesized that tumor necrosis
factor a levels in the circulation of diabetic subjects
are influenced by periodontal infection and inflammation (32). Tumor necrosis factor a has the potential to increase insulin resistance and make glycemic
control more difficult (34). Therefore, it has been
hypothesized that periodontal therapy may improve
the metabolic control of diabetes via improved
insulin sensitivity by reducing the peripheral concentration of tumor necrosis factor a. A significant
reduction in tumor necrosis factor a was correlated
with a significant diminution of total HbA1c levels
following periodontal treatment (34). Grossi et al.
(25) found that effective control of periodontal
infection in diabetic patients could reduce the levels
of advanced glycation end-products in the serum.

264

Significant improvements were also found in terms

of total volume of gingival crevicular fluid and the
levels of interleukin-1b and tumor necrosis factor a in
both diabetics and non-diabetics. Diabetic subjects
showed improvement in metabolic control demonstrated by the reductions in HbA1c levels (81).
Correa et al. (16) showed a tendency towards a decrease in circulating biomarkers, particularly tumor
necrosis factor a and fibrinogen, at 3 months after
treatment. The periodontal treatment regime also reduced the levels of high-sensitivity C-reactive proteins
and HbA1c (16). These circulating cytokines are the
common mediators of several adverse processes in the
human body. Reducing the levels of these mediators
retards the diabetic or cardiovascular disease process.
The use of adjunctive systemic medication has been
shown to improve the healing response following
mechanical periodontal therapy. Several studies have
used adjunctive medication, such as systemic doxycycline, with non-surgical therapy, and reported a
significant reduction in periodontal infection and
inflammation and a short-term reduction in HbA1c
levels (25, 34).
In periodontal therapy, reducing the bacterial
burden by root surface debridement targets only one
aspect of the periodontal pathogenic process. Complete elimination of all subgingival bacteria is not
achievable, and re-colonization occurs over a period
of time. Modulation of the host response offers the
potential to down-regulate destructive aspects of the
host response in combination with non-surgical
therapy, tipping the balance between resolution and
disease progression in the direction of a healing response.
Sub-antimicrobial doses of doxycycline have
been shown to reduce tissue destruction and stabilize
the periodontium by down-regulating modifying
destructive aspects and or up-regulating protective
components of the host response. Such doses have
the ability to modulate a variety of pro-inflammatory
pathways. They have been found to directly inhibit
active matrix metalloproteinases and oxidative activation of latent matrix metalloproteinases, to downregulate expression of key inflammatory cytokines
and to stimulate fibroblast function (17, 43). This
modulation of pathways will also lead to a reduction
in osteoclastic activity and bone resorption (23).

Conclusion
Periodontal diseases, which are prevalent in most
populations, may have wide-ranging systemic effects

Periodontal disease and diabetes

in susceptible individuals, and may act as a potential

independent risk factor for complications of diabetes
mellitus, exacerbating the existing disorder of the
patient. Biological plausible pathways support the
role of periodontal infections in the pathogenic mechanisms of diabetes mellitus. Fortunately, periodontitis is a readily modifiable risk factor. Patient
education is therefore a priority in both the medical
and dental fraternities, and prevention of periodontal
and oral infections should be emphasized, especially
in diabetic patients.
However, periodontal diseases are not the cause of
diabetes mellitus or other systemic diseases. Future
research is required to further delineate the role of
periodontal diseases in systemic health, and to substantiate the possible association between periodontal diseases and conditions such as diabetes
mellitus, cardiovascular disease and cerebrovascular
and respiratory diseases. Longitudinal studies and
intervention trials are required towards this end.
Multi-center studies utilizing identical protocols are
required to provide a clearer picture of this relationship in terms of prevalence, incidence and the effect
of treatment in the varied and vast Asia-Pacific
region.
In the observational and randomized trials already
performed, control of multiple risk factors decreased
diabetic complications by approximately 50% in
patients with type 2 diabetes (21, 38). There is a very
strong genetic predisposition with type 2 diabetes,
and obtaining a family medical history for each
patient is therefore important. It has also been
suggested that dentists could help to identify people
with diabetes by performing preliminary non-fasting
and even fasting plasma glucose testing. Periodontal
therapy may be of benefit in controlling the type 2
diabetes pandemic in Asia, together with concerted
integrated population-wide preventive approaches
such as diet counseling, early detection of the disease and smoking cessation. In addition, clinical
practice guidelines should be developed to facilitate
interaction between the medical and dental specialties to address the consequences of the interrelationship between diabetes mellitus and periodontal diseases. This has been attempted by the
Scottsdale Project (29), which brought together a
wide range of medical and dental experts to discuss
the association between diabetes, periodontal disease and cardiovascular disease, and propose a
trans-disciplinary model of care. These propositions
could be adapted and implemented in a similar
approach in the Asia region for the well-being of
affected patients.

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