SRM University Journal of Dental Sciences Volume 1 - Issue 1 - June 2010

Review
Diabetes mellitus – A periodontal perspective

Dr. Aruna Balasundaram*, Dr. Deepa Ponnaiyan**, Dr. Harinath Parthasarathy*

*Reader, **Senior Lecturer, Department of Periodontics,
SRM Dental College, Ramapuram, Chennai.

Address for correspondence:

ABSTRACT
Dr. Aruna Balasundaram
Reader, Diabetes mellitus is a heterogeneous metabolic disease characterized by impaired
Department of Periodontics, glucose tolerance and altered carbohydrate and lipid metabolism. Diabetes mellitus is
SRM Dental College and Hospital increasing in Indian Population and it's estimated to be 37 million by 2025 as predicted
Chennai - 89, by WHO. This is of greater significance for dental professionals as evidenced from
Tamilnadu, India. clinical research showing strong relationship between diabetes and periodontal
Cell: +91-9840162966 disease. Periodontitis is also referred as the “sixth” complication of diabetes. The
E mail id : bbaallaa2002@yahoo.co.in current review article highlights the clinical picture (i.e) diagnostic criteria and
periodontal implications of diabetes and also the two way inter relationship between
periodontitis and diabetes mellitus.

Periodontal treatment has favourable effects on glycemic control .Thus, importance of

maintaining periodontal health in diabetic patients is essential..

KEYWORDS: Diabetes, Prediabetic, Impaired glucose tolerance, Insulin resistance.

INTRODUCTION Among the various hormonal diseases, Diabetes mellitus is

Periodontal disease is a infectious multifactorial disease
caused by a small group of predominantly anaerobic gram-
ve bacteria present on the tooth surface as biofilm. Lipo
polysaccharides and other microbial substances gain access
to the gingival tissues, initiate and perpetuate inflammation,
resulting in high levels of pro inflammatory cytokines,
which causes destruction of tooth supporting structures.
Progression and severity of periodontitis are modulated by
bacterial and host immune response.
an extremely important disease from periodontal
standpoint.The increased prevalence and severity of
periodontitis, commonly seen in patients with diabetes
especially with poor metabolic control led to the designation
of periodontitis as the 6th complication of Diabetes Mellitus.3
The number of people with type 2 diabetes mellitus is
increasing in India due to increase in population with obesity
which is strongly associated with rapid changes in our
lifestyle such as increased sugar and lipid consumption.

Several risk factors play an important role in development of
periodontitis like age, specific bacteria, tobacco use, genetic
factors, preexisting disease, which influences host response
mechanism.1 Certain systemic disorders and conditions alter
host tissue physiology, which may impair host barrier
integrity and host defense to periodontal infection resulting
in more destructive disease.
In 1900, William Hunter, a British physician gave “Focal
Infection” theory which implied that there was a nidus of
infection, somewhere in the body, such as periodontitis,
which affect distant sites and organs via the blood stream.
The new look at emerging science, suggests that periodontal
infection can adversely affect systemic health with
manifestation such as coronary heart disease, stroke,
diabetes, Pre-term labor, low weight birth delivery,
respiratory disorders.2
Periodontitis is more prevalent in diabetic patients and
worsens diabetes. Also periodontitis results in impaired
glucose tolerance, a prediabetic state who are at higher risk
of developing diabetes. 4
Furthermore successful treatment appears to have a
beneficial role in the metabolic control of Type 2 diabetes
mellitus indicating that Diabetes mellitus not only influence
the pathophysiology of periodontal disease in a one-way
fashion, but periodontal disease in turn influence the disease
status in a reciprocal fashion5. Treating periodontal
infections can be influenced in contributing to glycemic
control as well for reduction of diabetic complications.
EPIDEMIOLOGY
The World Health Organization (WHO) has recently
acknowledged that India has the maximum number of

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Diabetes Mellitus - A Periodontal Perspective Aruna et al

diabetic patients than does any given country (around 35 through diet modification, in combination with oral
million). This is projected to increase to 57 million by the hypoglycemic agents, although insulin supply may also be
year 2025. India is thus the 'Diabetic Capital of the World'. used to achieve glycemic control.
Since 1975, there is a steady increase in the prevalence of
diabetes mellitus in rural dwellers of India. The prevalence GESTATIONAL DIABETES
has increased from 0.6% in 1975 to 2.4% in 1995.6 Though It is the glucose intolerance that begins during 3rd trimester of
the racial predilection of diabetes in Asian population is pregnancy. A history of gestational diabetes mellitus
known, scanty epidemiological studies have been done so increases the risk for subsequently developing Type II
far. diabetes.
The etiological spectrum of mortality in people with
diabetes at this Indian centre continues to be dominated by SIGNS AND SYMPTOMS
infections and renal failure, which is different from that in
the developed world, where coronary artery disease and General
cerebrovascular disease are the principal causes of General signs and symptoms are the direct result of
mortality. 7 Hyperglycemia which includes triad of polyuria,
polydypsia, polyphagia together with pruritis, weakness and
High morbidity and mortality in developing countries like fatigue.
India could be attributed to lack of awareness and less access
to medical care in rural areas. Oral
Burning mouth, altered wound healing, increased
?
DIABETES MELLITUS incidence of infection
Diabetes mellitus is a clinically and genetically Xerostomia, dry mucosal surfaces
?
heterogeneous group of metabolic disorders manifested by Increased incidence of oral candidiasis and dental
?
abnormally high levels of glucose in the blood. caries
Increased gingival inflammation
?
C L A S S I F I C AT I O N O F D I A B E T E S ?Tendency towards enlarged gingiva, gingival polyps,
8
MELLITUS periodontal abscess formation
Type I diabetes Increased risk of attachment loss and alveolar bone
?
Type II diabetes loss
Gestational diabetes
Other types of diabetes Diabetes mellitus doesn’t cause gingivitis or periodontitis,
Genetic defects in pancreatic beta cell function, insulin but it alters the response of periodontal tissues to local
action factors through impaired host response, excessive release of
pro inflammatory cytokines and tissue degrading enzymes.
Genetic defect in insulin action
?
Pancreatic diseases or injuries
?
COMPLICATIONS
Infections (Cytomegalo virus, Congenital rubella)
?
Five “classic” complications
? Drug Induced (Glucocorticoids) Retinopathy
?
? Endocrinopathies Nephropathy
?
Neuropathy
?
? Other genetic syndromes Macrovascular
?
? Cerebrovascular
? Cardiovascular
TYPE I DIABETES ? Peripheral vascular
This is Insulin Dependent Diabetes Mellitus, caused by the Altered wound healing
?
destruction of insulin producing beta cells of pancreas due to
autoimmune (or) virally mediated destructive process Proposed sixth complication
resulting in Insulin deficiency. This occurs in young, lean
individuals, before the age of 30 and accounts for 10% of all Periodontal diseases
?
cases of Diabetes mellitus.
ACUTE COMPLICATIONS OF DIABETES
TYPE II DIABETES
Non Insulin Dependent Diabetes mellitus is caused by
MELLITUS
peripheral resistance to insulin action, impaired insulin
secretion and increased glucose production by liver. This is Hypoglycemia
?
most common form of diabetes accounting for 90-95% of all Diabetic Ketoacidosis
?
cases, has an adult onset. These patients are managed
Hyperglycemic hyperosmolar state
?

80
Diabetes Mellitus - A Periodontal Perspective Aruna et al

Hypoglycemia
without proper treatment. It may be difficult to differentiate
The emergency most likely to occur in dental office is
between hypoglycemic and hyperglycemia in an
hypoglycemia (or) insulin shock which may get precipitated
unconscious diabetic patients. In this case treatment should
in the insulin using diabetic patients by excessive exercise,
be initiated for hypoglycemia as it may go for a life
stress, insulin over dosage. Severe hypoglycemia is a life
threatening condition.
threatening event and should be managed immediately.
Signs and symptoms of hypoglycemia occur only when
blood glucose levels falls below 60mg/dl.
DIAGNOSTIC CRITERIA
In 1998, the WHO adopted the diagnostic parameters
Signs and symptoms of hypoglycemia include mental
for diabetes established by the American Diabetes
confusion, shakiness, tremors, agitation, anxiety,
Association 10. There are 3 ways to diagnose diabetes. If any
diaphoresis, dizziness, tachycardia, feeling of “impending
of these criteria is found, it must be confirmed on a different
doom”, seizures, loss of consciousness.
day

Table: 1 American Diabetes Association Criteria for the diagnosis of Diabetes mellitus,
Impaired Glucose Tolerance (IGT) and Impaired Fasting Glucose (IFG)8

Normal Diabetes IGT IFG

Fasting glucose mg/dl <100 >126 100-125
Casual glucose(mg/dl) >200 plus symptoms
of diabetes
2 hour post load <140 >200 >140 but <200
glucose*(mg/dl)
*2 hour post load glucose using the 2 hour oral glucose tolerance test

Symptoms of diabetes plus casual plasma glucose

?
9
TREATMENT OF HYPOGLYCEMIA concentrations >126 mg/dl (>11.1mmol/l). “Casual” is
If the patient is conscious and able to take food by mouth defined as any time of the day without regard to time
give 15-20g oral carbohydrate since the last meal. The classic symptoms of diabetes
o 4-6 oz(140-200ml) fruit juice (or) include polyuria, polyphagia, polydypsia and
o 3-4 teaspoons table sugar(or) unexplained weight loss
o Hard candy Fasting plasma glucose >126mg/dl (>7.0mmol/l). Fasting
?
is defined as no caloric intake for at least 8 hours
If the patient is unable to take food by mouth and I.V line is ?2 hour post load glucose >200mg/dl (>11.1mmol/l)
in place during a 75g oral glucose tolerance test. The test should
o 30-40ml 50% dextrose in water(or) be performed using a glucose load equivalent of 75 g
o 1mg glucagon anhydrous glucose dissolved in water
If the patient is unable to take food by mouth and I.V line is
I M PA I R E D G L U C O S E TO L E R A N C E A N D
not in place
IMPAIRED FASTING GLUCOSE
o I.M glucagon subcutaneously (or) I.M There exists an intermediate group of individuals, whose
glucose levels are between normal and diabetes. Both IGT
Hyperglycemic crisis and IFG are considered as prediabetic state and they predict
This is less common in dental office. Diabetic ketoacidosis the future development of type II diabetes11.The American
have characteristic similar to that found in uncontrolled Diabetes Association has given the Criteria for the diagnosis
diabetes. In Type II diabetes patients, prolonged of Diabetes mellitus, Impaired Glucose To;erance and
hyperglycemia may cause hyperosmolar non ketotic impaired fasting glucose.
diabetic acidosis, in both there is loss of consciousness

81
Diabetes Mellitus - A Periodontal Perspective
DIAGNOSTIC AIDS
The primary method used to diagnose diabetes mellitus and
monitor blood glucose levels have been fasting blood
glucose, a combination of fasting blood glucose plus a 2
hour test after glucose loading, and oral glucose tolerance
test.
Casual (non- fasting) plasma glucose can also be used for
diagnosis
Glycated Hemoglobin test measures the amount of glucose
irreversibly bound to the hemoglobin molecule.This value is
proportional to blood glucose levels and gives a measure of
blood glucose status over the half life of RBC (30-90days).
Two different glycated hemoglobin tests are available:
HbA1 and HbA1c.
Nowadays chair side kits available to assess Hb A1c.12
HbA1c is used to monitor over all glycemic control in
diagnosed diabetic patients. Normal HbA1c is <6% and ≡
8% is poorly controlled.
Glycated Albumin and glycated fructosamine have been
developed as monitoring tools. Fructosamine levels provide
assessment of glycemic control over the past 4-6 months. It
is possible to screen for the presence of suspected diabetes
with a stick glucose self monitoring device using fingertip
capillary blood. This can be accomplished with gingival
blood produced by periodontal probing and the levels
produced from both these sources correlate.13
Urine testing – Presence of glucose in urine is detected by
generation of color changes on urine reagent strips.
Glycosuria occurs when plasma glucose exceeds renal
threshold 180mg/dl
IMPACT OF HYPERGLYCEMIA ON
PERIODONTIUM
Factors contributing to development of periodontal disease
in diabetic patients
? Polymorphonuclear Leukocyte function Impairment in
PMN chemotaxis, adherence and phagocytosis suggest
that this dysfunction can lead to impaired host response
to infection
? Altered collagen metabolism and Advanced Glycation
End Products (AGE)
Synthesis maturation and homeostasis of collagen appears
to be affected by glucose levels. There is reduced fibroblast
cell proliferation and growth, and reduced synthesis of
collagen and glycosaminoglycans and there is increase in
collagenase activity.
The formation of advanced glycation end products plays a
central role in diabetic complications. AGE accumulates
Aruna et al
with chronic hyperglycemia. AGE formation alters the
function of numerous extra cellular matrix components,
modifying matrix to matrix and cell to matrix interactions.
These alterations have an adverse affect on target tissues
especially collagen stability and vascular integrity. AGE
formation on collagen results in increased cross linking
between collagen molecules contributing to decreased
solubility and decreased turnover rate.
Monocytes, macrophages and endothelial cells possess high
affinity receptors for AGE products. AGE binding to
macrophage receptors, results in increased secretion of
interleukin 1, insulin like growth factor and tumor necrosis
factor alpha. While endothelial cell binding results in pro
coagulative changes leading to focal thrombosis and
vasoconstriction. AGE formation in gingival tissues have
been shown to increase oxidative stress which may be
responsible for vascular injury.
Infections and diabetes:
?
Defects in PMN function, induction in insulin resistance
and vascular changes can contribute to increased
susceptibility to infections
? Impaired wound healing
Poor wound healing is characterized by decrease in the
amount of collagen associated with lower tensile strength.
Decreased collagen synthesis by fibroblasts and increased
collagenase production play a role in decreased wound
healing. Glycosylation of existing collagen at the wound
margin results in reduced solubility and delayed
remodeling. Increased collagenase levels degrade newly
synthesized less completely cross linked collagen.
Defective wound healing maybe due to non enzymatic
glycosylation of collagen and other proteins during periods
of hyperglycemia. Also certain growth factors such as
platelet derived growth factor, epidermal growth factor,
transforming growth factor beta are thought to be limited at
the diabetic wound site which contributes to wound healing
impairment. Monocyte is the principal cell involved in
wound debridement and growth factor secretion.
Thus shifting monocyte phenotype from reparative
regenerative cell to inflammatory phenotype, maybe
responsible for impaired wound healing & exaggerated
inflammatory response. 14
Effect of diabetes on periodontal flora:
The composition of periodontal microflora found in
periodontally diseased sites of type 2 diabetes mellitus
patients appear to be similar to that found in chronic adult
periodontitis. Prevotella Intermedia, Campylobacter rectus,
Prophyromonas Gingivalis and Aggregatibacter
actinomycetemcomitans are most predominant pathogens
in subgingival dental plaque of type 2 diabetic patients15 .
There is an increased percentage of spirochetes, motile rods
and decreased levels of cocci seen in periodontal lesions in
poorly controlled diabetics.16
HLA – DR4 Predisposition:
Type 1 diabetes has been associated with specific human
82
Diabetes Mellitus - A Periodontal Perspective
lymphocyte antigens HLA–B 8 B 15. Approximately 90%
IDDM patients have DR3 & DR4 or both, DR3, DR4
molecules on peripheral blood cell antigens may increase
susceptibility to periodontitis14.
INFLUENCE OF PERIODONTITIS ON
DIABETIC STATE
Inflammation is hypothesized to play a significant role in
development of Type II DM and periodontal disease is a
known hyper inflammatory condition.
Diabetic patients with periodontal infections have a greater
risk of worsening glycemic control over time compared to
diabetic subjects without periodontitis17.
Fig 1: Schematic presentation of bi-directional relationship of TNF α in promoting insulin resistance 21
Periodontal disease is also considered as a risk factor for
cardiovascular diseases such as myocardial infarction and
stroke. In subjects with severe periodontitis, the mortality
rate from ischemic heart disease was 2.3 times higher than
the rate in subjects with no periodontitis or only slight
periodontitis9.
This observation may indicate that patients with
periodontits have impaired glycemic control and are in a pre
diabetic state and are prone to get diabetes
This impaired glucose tolerance may be due to insulin
resistance. Bacterial, viral infections increase insulin
resistance even in non diabetics making difficult for the
glucose to enter target cells which alters glycemic status.
83
Aruna et al
Biological mechanism linking periodontitis to impaired
glucose metabolism are inflammatory mediators such as IL-
6, IL -1 β, TNF-α , PGE2 generated within inflamed tissue
interfering with action of insulin receptors thereby
decreasing insulin sensitivity or cause insulin resistance.20
In periodontits it is well known that the lipopolysaccharides
continuously provided by gram negative bacteria, such as P
gingivalis trigger the production of poor inflammatory
cytokines and pro glycemic control.
Elevated levels of IL-1 β are thought to play a role in the
development of Type 1 diabetes .IL – 1 β facilitates protein
kinase C activation leading to pancreatic β cell destruction
through apoptotic mechanism.IL-6 is important in
stimulating TNF α production.TNF α – mechanisms by
which suppresses insulin action.21
TNFα phopshorylates a serine residue of the insulin
x
receptor substrate -1(IRS 1) and inhibits the tyrosine
phopshorylation essential for insulin signal
transduction.
xInduces intracellular hydrogen peroxide, which inhibits
tyrosine phophorylation of IRS-1.
xTNF α stimulates lipolysis in adipocytes to release free
fatty acids which are also thought to induce insulin
resistance. Successful periodontal treatment is reported
to decrease circulating TNF α in patients with
periodontal disease. Schematic presentation of bi-
directional relationship of TNF α in promoting insulin
resistance and periodontal inflammation (Grossi &
Genco 1998) (Fig1)21
Diabetes Mellitus - A Periodontal Perspective
Periodontal therapy may result in improved metabolic
control in many individuals with poorly controlled diabetes.
Diabetic patients are susceptible to infection and these can
Onocytes, macrophages and endothelial cells possess high
affinity receptors for AGE products. AGE binding to
macrophage receptors, results in increased secretion of
interleukin 1, insulin like growth factor and tumor necrosis
factor alpha. While endothelial cell binding results in pro
Fig 2: Reciprocal link between diabetes and periodontitis
coagulative changes leading to focal thrombosis and
vasoconstriction .AGE formation in gingival tissues have
been shown to increase oxidative stress which may be
responsible for vascular injury In the present day scenario
of evidence based dentistry, it will be apt to treat the
individuals who are at potential risk with some strong
evidence rather than empirical treatment. A simple chair side
diagnostic assay like BANA test could be useful to identify
individuals who are at higher risk for periodontal diseases.
Based on the results of the study, BANA test could be used as
a reliable indicator of periodontal disease activity in
smokers.
ANTIBIOTIC USAGE IN DIABETES
Antibiotics are not necessary for routine dental procedures
in diabetic individuals but are considered in the presence of
overt oral infection, due to the potential for lowering host
resistance and delayed wound healing in diabetic patients.24
Tetracyclines, doxycyclines are used along with mechanical
debridement. Tetracyclines along with their antimicrobial
effect, has a modulatory effect on host response by
suppressing or inhibiting collagenolytic process and
increasing protein synthesis.
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Aruna et al
Tetracyclines cause the retention of membrane associated
TNF α thereby preventing the release of TNF α form the
monocyte membrane. Tetracycline has also been found to
block protein kinase C activity an important step in secretion
of interleukin 1 β and TNF α in LPS stimulated human
monocytes14.
Root surface debridement is necessary to disrupt sub
gingival biofilm. This fundamental requirement of
periodontal therapy is even more relevant in patients whom
periodontal infection constitutes a health risk such as
suffering from diabetes mellitus.
There was a good reduction in blood glucose levels in
diabetic patients when mechanical treatment done with
systemic adjunctive antibiotics compared to mechanical
treatment alone or mechanical treatment and locally
administered adjunctive antimicrobials23.
Doxycycline along with anti infective periodontal treatment
in diabetic patients has a dual benefit, first as broad
spectrum antibiotic and its concentrations in gingival fluid is
7 to 10 fold over serum levels which reduces periodontal
pathogens. Second, as a potent modulator of diabetic
patients host response to periodontal infection. Doxycycline
inhibits non enzymatic glycation of extra cellular protein.
TIMING OF TREATMENT
Procedures should be short atraumatic and as stress free as
possible. Stress free situations increase production of
endogenous catecholamines and cortisol which increase
blood glucose levels.Providing profound anesthesia,
reducing post operative discomfort through use of
analgesics will help to reduce fluctuations in blood glucose
levels.
Diabetes Mellitus - A Periodontal Perspective
Periodontal treatment can be timed appropriately during the
day to avoid peak insulin activity; Periodontists must be
aware of risk of hypoglycemia during dental appointment
and be ready to manage emergencies.
IMPLANTS IN DIABETIC PATIENTS
Although there is a slight tendency for more failures of
implants in a diabetic compared to a non diabetic
population, the increased risk is not substantial in patients
who are under good metabolic control. In the general
population the five year overall success rate for implants is
approximately 95% whereas in a diabetic population the rate
is approximately 86%.diabetes with Hb A1 c values of ≡8%
are under poor control and have an elevated risk of
encountering defective wound healing,complicating osseo
integration 25.
CONCLUSION
Periodontal diseases and diabetes mellitus are closely
associated and are highly prevalent chronic diseases with
many similarities in pathobiology. Periodontitis is a risk
factor for poor glycemic control and treating periodontitis,
has a beneficial effect on blood glucose levels thereby
preventing diabetic complications.
Also as periodontitis is significantly associated with
impaired glucose tolerance, all subjects with poor
periodontal health can be screened for impaired glucose
tolerance, who are at a risk for diabetes mellitus at a future
date.
Diabetes clearly increases the risk of periodontal diseases,
and biologically plausible mechanisms have been
demonstrated in abundance. Less clear is the impact of
periodontal diseases on glycemic control of diabetes and the
mechanisms through which this occurs .It is possible that
periodontal diseases may serve as initiator or propagators of
insulin resistance in a way similar to obesity, there by
aggravating glycemic control. Further research is needed to
clarify this aspect of the relationship between periodontal
diseases and diabetes.
To conclude prevention and control of periodontal disease
must be considered an integral part of diabetic control.
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