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