DIABETES AND PERIODONTAL DISEASES

CONTENTS• INTRODUCTION• DEFINITIONS• HISTORY• EPIDEMIOLOGY• CLASSIFICATION• DIAGNOSIS• INSULIN & DIABETES• CLASSICAL SIGNS, SYMPTOMS & COMPLICATIONS OF DM• DIABETES AND PERIODONTAL DISEASE• DENTAL THERAPY CONSIDERATIONS• CONCENSUS REPORT- EFP/AAP JOINT WORKSHOP• CONCLUSION• REFRENCES

DEFINITIONS

International Diabetes Federation (IDF) describes Diabetes as a chronic disease that arises when the pancreas does not

produce enough insulin, or when the body cannot effectively use the insulin it

produces.

According to Carranza, DM is defined as a complex metabolic disorder characterized

by chronic hyperglycaemia, diminished insulin production, impaired insulin action

or a combination of both result in the inability of glucose to be transported from the blood stream into the tissues, which in

turn results in high blood glucose levels and excretion of sugar in the urine.

HISTORY

EPIDEMIOLOGY According to International Diabetes Federation (2012), there are more than 371 million people in world who have diabetes. The number of people with diabetes is increasing in every country in which half of people with diabetes are undiagnosed. The estimate of the actual number of diabetics in India is around 40 million.

India and Diabetes• Diabetic Capital of the world (40.9 million)• Followed by China, USA, Russia, Germany• 12% of urban population suffer from diabetes• Less than 3% Rural population• Obesity and Hypertension are major risk factors in India• Southern Indians have an increased risk of DM through inheritance, the

changes in dietary habits and less physical activity as a result of urbanization and modernization.

• The prevalence of micro and macrovascular complications in Indian people with diabetes is high.

• One out of every 12 Indians above the age of 40 is a diabetic

(International Diabetic Foundation, 2007)

CLASSIFICATIONS

National Diabetes Data Group(1979)- on the basis of age at onset and type of therapy:

• TYPE I- Insulin dependent DM (IDDM) or Juvenile Diabetes

• TYPE II- Non insulin dependent DM (NIDDM) or Adult onset Diabetes

American diabetic association (1997)

DM is classified on the basis of pathophysiology of DM into 4 categories:

1. Type 1 2. Type 2 3. Other Specific types of

DM4. Gestational diabetes

This is a condition called pre-diabetes. These individuals are normoglycemic but demonstrate

elevated blood glucose levels after fasting and after glucose load. This condition is a strong predictor for

future development of type 2 DM (Mealey & Ocampo 2007).

Impaired glucose tolerance and impaired fasting glucose

CARBOHYDRATE METABOLISM, INSULIN AND DIABETES

BLOOD GLUCOSE HOMEOSTASIS

ACTIONS OF INSULIN

Characteristics of Type I and Type II Diabetes

GESTATIONAL DIABETES

• Under normal conditions insulin secretion is increased by 1.5 to 2.5 fold during pregnancy reflecting a state of insulin resistance

• Gestational diabetes develops in 2% to 5% of all pregnancies but disappears after delivery.

• Women who have had gestational diabetes are at increased risk of developing type 2 diabetes later in life.

• It usually has its onset in the third trimester of pregnancy and adequate treatment will reduce perinatal abnormality.

CLASSICAL SIGNS & SYMPTOMS

It includes polydypsia, polyphagia, polyuria, pruritis, weakness & fatigue. (More common on type 1) occur in varying degree in type 2 DM.

Type 1 DM may associated with Weight loss, Ketoacidosis Restlessness, irritability & apathy may become evident.

THE CLASSIC COMPLICATIONS OF DM

1. Diabetic Retinopathy2. Diabetic Neuropathy3. Diabetic Nephropathy4. Atherosclerosis5. Impaired wound healing 6. Periodontal disease (Loe H

1993)

Acute Complications of Diabetes Mellitus

• Diabetic ketoacidosis• Hyperosmolar non-ketotic diabetic coma• Hypoglycemia• Lactic acidosis

Oral Diseases and Diabetes

Oral manifestations and complications

No specific oral lesions associated with diabetes. However, there are a number of issues of concern

• Oral neuropathies – Burning mouth syndrome– Burning tongue– Temporomandibular joint dysfunction (TMJD)– Depapillation and fissuring of the tongue. (Martin Gillis et al 2003)

• Salivary glands– Xerostomia is common,

but reason is unclear.– Tenderness, pain and

burning sensation of tongue.

– May secondary enlargement of parotid glands.

• Dental caries– Increase caries

prevalence in adult with diabetes. (xerostomia, increase saliva glucose)

– Hyperglycemia state shown a positive association with dental caries.

• Cheilosis

• Alteration of flora of oral cavity – Predominance of candida albicans

Cracking of Oral MucosaIncreased tooth sensitivity

Enamel HypoplasiaMultiple periodontal abscesses

Increased risk of infection• Reasons unknown, but macrophage metabolism altered

with inhibition of phagocytosis.• Thickening of vascular endothelium – altering tissue

hemostasis• Peripheral neuropathy and poor peripheral circulation • Immunological deficiency• High sugar medium• Decrease production of Ab• Candidial infection are more common and adding effects

with xerostomia

Diabetes and Periodontal Diseases

PERIODONTAL MANIFESTATIONS Hirchfeld I (1934)

• Tendency towards enlarged gingiva.

• Sessile/pedunculated gingival polyps.

• Ploypoid gingival proliferations

• Abscess formation• Periodontitis• Loosened teeth

Gingivitis

Higher risk of developing gingivitis

(Jenkins et al 2001)

Diabetes is a risk factor for gingivitis and

periodontitis, and the level of glycemic

control appears to be an important

determinant in this relationship.

(Papapanou et al, 1996 & Mealey et al,

2000 )

The prevalence of gingivitis in children and adolescents is nearly twice when compared with non

diabetics (DePommereau  et

al 1998)

“Diabetes mellitus- associated

Gingivitis” – Specific entity in the recent

classification of gingival diseases ( Holmstrup et al

1999 Ann Periodontol)

Poor metabolic control can increase the severity of gingival inflammation in diabetic children (Gusberti et al ,

1983 ) whereas improvement in glycemic control may be associated

with decreased gingival inflammation (Karjalainen et al, 1996)

EFFECT OF DIABETES ON PERIODONTITIS

Data of multiple studies reveal strong evidence

•Diabetes is a risk factor for gingivitis & periodontitis.•The level of glycemic control appears to be an important determinant in this relationship.

Cianciola et al

1982 In children with type 1 diabetes, the prevalence of gingivitis was greater than in non-diabetic children with similar plaque levels.

Sastrowijoto S et al

1990 Improvement in glycemic control may be associated with decreased gingival inflammation.

Papapanou PN

1996 Majority of the studies demonstrate a more severe periodontal condition in diabetic adults than in adults without diabetes.

Tsai C et al 2002 In a large epidemiologic study in the United States, adults with poorly controlled diabetes had a 2.9-fold increased risk of having periodontitis compared to non-diabetic adult subjects; conversely,well-controlled diabetic subjects had no significant increase in the risk of periodontitis.

Salvi GE et al

2005 Rapid and pronounced development of gingival inflammation in relatively well-controlled adult type 1 diabetic subjects than in non-diabetic controls, despite similar levels of plaque accumulation and similar bacterial composition of plaque, suggesting a hyperinflammatory gingival response in diabetes.

Lalla et al 2007 Type 1 350 diabetic patients with periodontitis who shown gingivitis and loss of periodontal attachment shown a positive co-relation of pregestational diabetes and an increased risk of periodontal diseases in later life

Demmer at al

2008 In a 2-year longitudinal trial, 625 diabetic subjects with periodontitis patients shown that periodontal diseases is an independent predictor of incident diabetes mellitus type 2

Vieira Ribeiro et al.

2011

20 adults with poorly controlled T2DM and chronic periodontitis, 17 adults with well-controlled T2DM and chronic periodontitis and 20 systemically healthy adults with chronic periodontitis were taken and it was found that OPG, RANKL, IFNγ, IL-17 and IL-23 were elevated in T2DM patients with chronic periodontitis as compared to systemically healthy patients with chronic periodontitis

EFFECT OF PERIODONTAL DISEASE ON DIABETES

• Periodontal diseases can have a significant impact on the metabolic state in diabetes. The presence of periodontitis increases the risk of worsening of glycemic control over time.

Williams RC Jr., Mahan CJ.

1960 Type 1 diabetic patients with periodontitis had a reduction in required insulin doses following scaling and root planing, localized gingivectomy, and selected tooth extraction combined with systemic procaine penicillin G and streptomycin

Taylor GW et al 1996 In a 2-year longitudinal trial, diabetic subjects with severe periodontitis at baseline had a six-fold increased risk of worsening of glycemic control over time compared to diabetic subjects without periodontitis

Rodrigues DC et al

2003 Better improvement in glycemic control in a diabetic group treated with scaling and root planing alone compared to diabetic subjects treated with scaling and root planing plus systemic amoxicillin/clavulanic acid.

Promsudthi A et al

2005 In older, poorly controlled type 2 diabetic subjects who received scaling and root planing plus adjunctive doxycycline showed a significant improvement in periodontal health but only a non significant reduction in HbA1c values.

Demmer et al 2008 Performed a longitudnal study of 9296 patients between the age group of 25-74 and found out that subjects with periodontal diseases shown a two fold increase in the chance of having DM; as well patients with advanced periodontal diseases shown higher risk of type 2 DM

Koromantoz et al

2011 In a randomised controlled trial of 30 periodontal patients where primary periodontal therapy and oral prophylaxis was performed for every 7 days till 6 months shown that there was a significant reduction in HbA1c levels in the patients post treatment

Factors of Diabetic influence on Periodontium (Oliver and Tervonen, 1994 )

Sub gingival microbiota

GCF Glucose levels

Periodontal vasculature Host response

Collagen metabolism

Subgingival microbiota

Some studies reported higher proportions of Capnocytophaga species from periodontal lesions with type 1 diabetes ( Mashimo et al, 1983 )

Periodontally diseased sites in diabetic patients harbor similar species as comparable in non diabetic individuals. (Christagu et al JCP 1998, Sastrowijoto et al JCP 1989)

The proportion of P gingivalis was reported to be higher in non-insulin-dependent diabetes mellitus patients with periodontitis. This may be due to the abnormal host defense mechanisms in addition to hyperglycemic state can lead to the growth of particular fastidious organisms. (Zambon et al,1988)

GCF Glucose levelTwice increased amount of glucose in GCF of diabetic patients (Ficara et al JPR 1975)The function of immune cells, including neutrophils, monocytes and macrophages is altered in diabetes. Neutrophil adherence, chemotaxis, and phagocytosis are often impaired, which may inhibit bacterial killing in the periodontal pocket and significantly increase periodontal destruction.(Mc Mullen et al, 1981).Decreased chemotaxis of periodontal fibroblasts to PDGF in a hyperglycemic environment ( Nishimura et al. 1998 Ann Perio)

Thus, affects periodontal wound healing and also host response to microbial challenge.

Periodontal VasculatureBasement membrane of the endothelial cells of gingival capillaries are thickened (Frantzis et al. 1971 JOP, Listgarten et al.1974 JOP, Seppala et al.1997 JOP)

Leads to impaired oxygen and nutrient supply

Two fold increase in AGE in diabetic gingiva ( Schmidt et al 1996)

Leading to wide spread vascular injury

AGEs

Plays central role in diabetic complications . Alter functions of extracelluar matrix . Affects collagen stability and vascular integrity.

AGEs formation on collagen

Increased crosslinking between collagen molecules Reduced solubility . Decreased turn over rate .

ADVANCED GLYCATION END PRODUCTS (AGEs)

Hyperglycemic state

Non enzymatic Glycosylation of

proteins and matrix molecules

AGEs + Macrophages & Monocytes

Increased Secretion of IL-1, IGF, TNF ἀ

AGEs

AGEs + Endothelial cells

•Focal thrombosis•Vasoconstriction

Pre-coagulatory changesHyper-cellular state

AGEs AND PERIODONTIUM

AGE-RAGE interaction (monocytes)

↑ cellular oxidant stress and activates the transcription factor nuclear factor- kappa B (NF-kB)

alters the phenotype of monocyte/macrophage

↑ production of proinflammatory cytokines IL-1b and TNF-a.(Schmidt et al, 1999)

formation of atheromatous lesions in the larger blood vessels.(Ross et al, 1999)

interaction between the RAGE and AGEs in periodontal tissues

marked ↑ in gingival crevicular fluid levels of IL-1b, TNF-a, and prostaglandin E2 (PGE2) seen in diabetic subjects compared to non-diabetic individuals.(Engebretson et al,

2004)

These proinflammatory cytokines contribute to the pathogenesis of periodontal diseases and probably play a major role in patients with diabetes, especially when glycemic

control is poor.

The formation of AGEs also occurs in the periodontium, and higher

levels of periodontal AGE accumulation are found in those

with diabetes than in non-diabetic subjects.(Schmidt A et al,

1996)

AGEs often form on collagen, increasing collagen cross-linking and resulting in the formation of

highly stable collagen macromolecules.

Furthermore, improved glycemic control has been associated with reduced AGE-collagen formation.

(Odetti et al, 1996)

In diabetic animal models, blocking the receptor RAGE

decreases TNF-a, IL-6, and matrix metalloproteinase (MMP) levels in

the gingiva, diminishes AGE accumulation in periodontal

tissues, and decreases alveolar bone loss in response to P.

gingivalis.(Lalla et al, 2000)

Host Response

Collagen Metabolism

Reduced synthesis of collagen & glycosaminoglycans

Reduced collagen

maturation

Collagen homeostasis-

Affected

GCF collagenase activity increased

Hyperglycemic state

DIABETES INFLUENCE ON PERIODONTAL DISEASES

MECHANISM BY WHICH PERIODONTAL DISEASE MAY INFLUENCE DIABETES

2- WAY RELATIONSHIP BETWEEN PERIODONTAL DISEASE AND DM

PATHOGENESIS OF PERIODONTITIS IN DIABETES

Taylor JJ. JOP 2013

LINKAGE BETWEEN INFECTION,HYPERLIPIDEMIA & INSULIN RESISTANCE

INFECTIONS IN PATIENTS WITH DIABETES

Mainly due to:• Impaired defence mechanism 1. Defects in PMN function2. Induction of insulin resistance3. Vascular changes

Hyperglycemic state

Glycosylation of basement mem, proteins

• Thickning of gingival capillaries,

• Disruption of BM

Swelling of Endothelium

1. Oxygen diffusion2. Metabolic waste elimination

3. PMN Migration4. Diffusion of serum factors

Impeded

WOUND HEALINGWound Healing is Affected as cumulative effect of:

•Altered cellular activity•Decreased collagen synthesis

•Glycosylation of existing collagen

•Increase collagenase production

Readily degrade newly synthesized, less completely cross linked collagen

•Reduced Collagen solubility•Delayed remodelling of wound site

Defective Healing

Assessment of Glycemic Control

LABORATORY DIAGNOSISBLOOD TESTING

1. GLUCOSE

LABORATORY DIAGNOSIS2. Glycated Hemoglobin

URINE TESTING

1. GLUCOSE

Testing the urine for glucose with dipsticks is a common screening procedure for detecting diabetes.

2. KETONES

Ketone bodies can be identified by the nitroprusside reaction, which measures acetoacetate, using either tab lets or dipsticks.

3. PROTEIN

Standard dipstick testing for albumin detects urinary albumin at concentrations > 300mg/L

Home Blood Glucose Monitoring

Treatment

EFFECTS OF DIABETES ON THE RESPONSE OF PERIODONTAL THERAPY

• Many diabetic patients show improvement in clinical parameters of disease immediately after therapy, patients with poorer glycemic control may have a more rapid recurrence of deep pockets and a less favorable long-term response.

• Further longitudinal studies of various periodontal treatment modalities are needed to determine the healing response in individuals with diabetes compared to individuals without diabetes.

Pharmacological therapy :

Insulin Dewitt et al 2003

Syringe Pen

Pump Insulin Inhaler

Mode of administration of

Insulin

Anti-AGE Therapies • It include Aminoguanidine, ALT-946, ALT 711, Statins

(Cervistatin)• Pyridoxamine, the natural form of vitamin B6, is

effective at inhibiting AGEs at 3 different levels.– prevents the degradation of protein-Amadori

intermediates to protein-AGE products.– In diabetic rats, pyridoxamine reduces hyperlipidemia and

prevents AGE formation.– scavenges the carbonyl byproducts of glucose and lipid

degradation– Benfotiamine, a lipid-soluble thiamine derivative, inhibits

the AGE formation pathway.

Dental management considerationsTo minimize the risk of an intraoperative emergency, clinician

need to consider the following before initiating dental treatment.

• Medical history :– Patient’s family history of diabetes mellitus– Type of diabetes– Age of onset and duration of the disease– Current medications and their method of administration. – Patient’s degree of compliance should be discussed. – Previous history of diabetic complications– Determine the most recent laboratory results of Glucose levels– Record the name and address of the patient’s physician(s).– Frequency of hypoglycemic episodes

Dental management considerations

• Scheduling of visits– Morning appt. after breakfast– Short treatment procedures ( 2 hrs or less)– As atraumatic treatment as possible – Do not coincide with peak insulin activity.

• Diet– Ensure that the patient has eaten normally and taken medications as usual.

• Blood glucose monitoring– Measured before beginning. (<70 mg/dL)

• Prophylactic antibiotics – Established infection – Pre-operation contamination wound – Major surgery

Dental management considerations

• During treatment– The most common complication of DM is hypoglycemic episode.– Hyperglycemia

• After treatment– Infection control– Dietary intake

Periodontal Treatment and Diabetes

– Clinician should make sure that prescribed insulin has been taken, followed by a meal

– Morning appointments are appropriate because of optimal insulin levels– Monitor vitals, including blood glucose prior to treatment– Procedures performed may alter the patient’s ability to maintain caloric intake,

therefore post-op insulin doses should be altered accordingly– Tissues should be handled as atraumatically and minimally as possible (less

than 2 hrs)– Epinephrine should not be used in concentration greater than 1:100,000 due to

epinephrine effects on insulin—increases insulin use and deplete insulin levels more quickly

– Diet recommendations should be made to maintain proper glucose balance– Frequent recall and fastidious home oral care should be stressed

(Grossi, et al. JOP, Vol. 68, No. 8)

DENTAL IMPLANT CONSIDERATIONS IN THE DIABETIC PATIENT

• Diabetes-induced changes in bone formation:

• Inhibition of collagen matrix formation

• Alterations in protein synthesis• Increased time for

mineralization of osteoid• Reduced bone turnover• Decreased number of

osteoblasts and osteoclasts• Altered bone metabolism• Reduction in osteocalcin

production

Possible Diabetic Disturbances in Implant Wound Healing Process In Implants

DIABETIC EMERGENCIES

• Hypoglycemic crisis• Hyperglycemic crisis

MANAGEMENT OF HYPOGLYCEMIA

FACTORS THAT INCREASE THE RISK OF HYPOGLYCEMIA

Skipping or delaying food intake

Injection of too much insulin

Injection of insulin into tissue with high blood flow (eg, injection into thigh after exercise such as running)

Increasing exercise level without adjusting insulin or sulfonylurea dose.

Inability to recognize symptoms of hypoglycemia

Denial of warning signs or symptoms

Past history of hypoglycemia

Hypoglycemia unawareness

Low

Bloo

d Gl

ucos

e• Sign & symptoms occurs as fall in blood glucose

level below 60 mg/dl. • Severe hypoglycemia refers to fall in blood glucose

concentration below 40 mg% (2.2-mmol/1) requiring help from outside for recovery.

SIGN & SYMPTOMSLo

w Bl

ood

Gluc

ose

Severe hypoglycaemia may result in seizures or loss of consciousness.

The most common emergency related to DM in the dental office and a potentially life-threatening situation that must be recognized and treated expeditiously.

MENTAL CONFUSION, SUDDEN MOOD CHANGELETHARGY,….TACHYCARDIA , NAUSEA,

COLD CLAMMY SKIN, HUNGER, INCREASED GASTRIC MOTILITY, HYPOTENTION ,

HYPOTHERMIA.

Low

Bloo

d Gl

ucos

eIf patient is

UNCONSCIOUS

Give 50 ml of 50% intravenous glucose- through a large vein to avoid thrombophlebitis.

As soon as patient recovers consciousness, start oral carbohydrate intake, otherwise 5-10% glucose infusion has

to be continued till patient recovers consciousness.

Intramuscular injection of 1.0 ml of glucagon may be given if hypoglycaemia is insulin induced. It promotes

glycogenolysis, gluconeogenesis.

If patient does not regain consciousness inspite of normal blood glucose levels, then cerebral oedema is likely possibility which should be treated with intravenous

dexamethasone or mannitol.

Repeated hypoglycaemic episodes are hazardous for CNS; hence, one should find out the cause and treat it

or correct it by adjusting the patient's therapy.

Low

Bloo

d Gl

ucos

eIf patient becomes

CONSCIOUS

PREVENTION

ADMINISTRATION OF 15g OF ORAL CARBOHYDRATE (JUICE,CANDY)

MANAGEMENT OF HYPERGLYCEMIAHi

gh B

lood

Glu

cose

• A medical emergency from hyperglycemia is less likely to occur in the dental office since it develops more slowly than hypoglycaemia.

It occurs when blood glucose levels over 200mg/dl for extended period of time.

In Type 1 DM- ketoacidosis may occur- Characterized by- Disorientation, rapid & deep breathing, hot drying skin &

acetone breath.

Type 2 DM- hyperosmolar non-ketotic diabetic acidosis.Severe hypotention & Loss of consciousness occurs if left

untreated.

High

Blo

od G

luco

se

• Under some instances, severe hyperglycemia may present with symptoms mimicking hvpoglycemia.

• If a glucometer is not available, these symptoms must be treated as hypoglycemia.

Care is initiated by activating the emergency medical system, opening the airway, and administering oxygen. Circulation and vital signs should be maintained and monitored, and the patient should be transported to a hospital .

DIABETES & PERIODONTAL DISEASE: CENSUS REPORT OF THE JOINT EFP/AAP WORKSHOP ON PERIODONTITIS & SYSTEMIC DISEASES (CHAPPLE LC,GENCO R. J PERIODONTOL 2013)

GUIDELINE- A[Suggested Guidelines for physicians and other medical health professions for Use in Diabetes

Practice]

• Patients with diabetes should be told that periodontal disease risk is increased by diabetes.

• If they suffer from periodontal disease, their glycaemic control may be more difficult, and they are at higher risk for diabetic complications such as cardiovascular and kidney disease.

• Patients with type 1, type 2 and gestational diabetes should receive a thorough oral examination, which includes

comprehensive periodontal examination.• For all newly diagnosed type 1 and type 2 diabetes patients,

subsequent periodontal examinations should occur & annual periodontal review is recommended.

• For children and adolescents diagnosed with diabetes, annual oral screening is recommended from the age of 6–7 years by referral to a dental professional.

GUIDELINE- B[Suggested guidelines for use in dental practice]

• If periodontitis is diagnosed, manage it properly. If not, patients with diabetes should be placed on a preventive care regime and monitored regularly for periodontal changes.

• Patients with diabetes presenting with any acute oral/periodontal infections require prompt oral/ periodontal care.

• Patients with diabetes who have extensive tooth loss should be encouraged to pursue dental rehabilitation to restore adequate mastication for proper nutrition.

• Provide oral health education.• Patients who present without a diabetes diagnosis, but at risk for

type 2 diabetes and signs of periodontitis should be informed about their risk for having diabetes, assessed using a chair-side HbA1C test, and/or referred to a physician for appropriate diagnostic testing and follow-up care.

GUIDELINE- C [Recommendations for patients with diabetes at the physician’s practice/ office]

• If your physician has told you that you have diabetes, you should make an appointment with a dentist to have your mouth and gums checked. This is because people with diabetes have a higher chance of getting gum disease. Gum disease can lead to tooth loss and may make your diabetes harder to control.

GUIDELINE- D [Recommendations for patients at the dental surgery/office who have diabetes or are found to be at risk for diabetes]

• People with diabetes have a higher chance of getting gum disease. If you have been told by your dentist that you have gum disease, you should follow up with necessary treatment as advised.

• If you do not have diabetes, but your dentist identified some risk factors for diabetes including signs of gum disease, it is important to get a medical check-up as advised.

CONCLUSION• Diabetes mellitus has significant impact on tissues throughout the

body, including the oral cavity. As research indicates that poorly controlled diabetes increases the risk periodontitis.

• Alteration in host defence and tissue homeostasis appear to play

a major role.

• Advances in medical management of DM require a heightened awareness by the periodontist in the various treatment regimens used by diabetic patients.

• Familiarity with various medications, monitoring equipments, and devices used by diabetic patient allows provision of appropriate periodontal therapy while minimizing the risk of complications.

REFERENCES• Taylor JJ, Preshaw PM, Lalla E. A review of the evidence for

pathogenic mechanisms that may link periodontitis and diabetes. J Periodontol 2013;84:S113-S34.

• The position paper on diabetes & periodontal disease. J Periodontol 2000;71:664-78.

• Grossi SG, Genco RJ. Periodontal Disease and Diabetes Mellitus: A Two-Way Relationship. Ann Periodontol 1998;3:51-61.

• Periodontal Medicine Rose, Cohen• Carranza’s Clinical Periodontology 11th edition• Davidson’s Principles and Practice of Medicine 21st edition

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