oral manifestation of diabetes mellitus and periodontitis ,mechanisms

2. Good morning

3. Diabetes mellitus and periodontal diseases
PART II

4. Contents
 INTRODUCTION
 CLASSIFICATION
 METABOLIC ROLE OF INSULIN
 TYPE 1- DIABETES
 TYPE-2 DIABETES
 CLINICAL PRESENTATION OF DIABETES
 DIAGNOSIS OF DIABETES
 COMPLICATIONS OF DIABETES
 PATHOGENESIS OF COMPLICATIONS OF DIABETES
 ORAL MANIFESTATIONS OF DIABETES
 DIABETES & PERIODONTAL DISEASE
 DENTAL MANAGEMENT OF DIABETES
 CONCLUSION

5. Oral manifestations of diabetes
 Oral conditions that are seen in individuals with diabetes may include:
Alterations in salivary flow and constituents
Increased incidence of infection
Burning mouth
Xerostomia & parotid gland enlargement
Chelosis
Mucosal drying & cracking
Alterations in the flora of oral cavity with greater predominance of candida
albicans , streptococci & staphylococci.
Increase incidence of dental caries which may be associated with
decreased salivation or increased glucose concentration in the saliva &
GCF.

6. Effect of diabetes on dental caries is unclear.
Jones et al 1992…….increased caries in diabetes ……
De Paola et al 1993…….decreased caries rates in patients with diabetes
compared with individuals without diabetes…..
In some studies coronal and root caries rates were the same for diabetic and non
diabetic study groups.

7. POOR ORAL HYGEIN WITH EXCESS CALCULUS FORMATION

8. TENDENCY FOR PROGRESSIVE CARIES

9.  A degree of periodontal destruction that is not commensurate
with the level of local factors is often a clue to the presence of
underlying systemic diseases such as diabetes.

10.  Patients with poorly controlled or previously undiagnosed diabetes may
have multiple periodontal abscesses, exophytic tissue extending from
the periodontal pocket, mobile or displaced teeth and severe bone loss.

11. MULTIPLE RECURRENT ABSCESS

12. CHRONIC PERIODONTITIS WITH SUPPURATION AND MOBILITY

13. DIABETES & PERIODONTAL DISEASE
 Diabetes is a risk factor for periodontal disease
 (sixth complication)
 Studies have clearly proven that diabetes increases the risk of both severity &
incidence of periodontal disease progression.
 increased gingival inflammation may be seen in diabetic subjects even though
plaque levels are similar to non diabetic control.
 Further in addition , it has been shown that periodontal destruction was more
severe in diabetic patients with greater bone loss & attached loss.

14. The prevalence of periodontitis in diabetic adolescents ,young adults and adults
is significantly greater than similar aged non diabetic individuals
In large population studies type II diabetes has been shown to be a significant
risf factor for periodontitis – PAPANOU
By TAYLOR , diabetes may influence not only the prevelance and severity of
periodontitis but also the prognosis of the disease.

15.  Papapanou et al and Taylor et al 2001…….diabetes is a risk factor for
increased prevalence and severity of gingivitis. (Annals of
Periodontology 2001)
 Knuttila et al 1996,…. patients with poorly controlled diabetes have
significantly increased gingival redness, swelling, or bleeding
compared with both individuals without diabetes and patients with
well controlled diabetes.

16.  Taylor et al 2001……21 studies of children, adolescents, or adults with type 1
diabetes since 1968,… 20 studies….greater severity of periodontal disease in
patients with diabetes compared with non-diabetics.
 Genco et al 1990 & Emrich et al 1991…..type 2 diabetes….increased attachment
loss and alveolar bone loss by approximately threefold compared with non-
diabetics.

17. Periodontal disease
 Infections of periodontal origin are chronic, mostly Gram-negative, not only
affecting the tissues surrounding the tooth, but also constituting a systemic
challenge to immunocompetent cells and cells active in the inflammatory
cascade.
 Bacteremias of dental origin, the classic example of systemic spread of oral
infections, are not only frequent but also directly related to the severity of
gingival inflammation.
 Offenbacher provided a comprehensive review on the pathogenesis of
periodontal disease and the role of bacterial products and inflammatory
mediators responsible for tissue destruction.

18. PERIODONTAL PATHOGEN
ENDOTOXIN, TOXINS, CELL
MEMBRANE PRODUCTS
PROINFLAMMATORY
CASCASDE
SECRETION TNF –  + IL- 1
CONNECTIVE TISSUE
DESTRUCTION BONE
RESORPTION
SCHEMATIC MODEL OF THE
PATHOGENESIS OF
PERIODONTAL DISEASE : “INFECTION –
MEDIATED”

19. AGE – Protein
Macrophage
AGE-receptor
Syntehsis + Secretion
TNF –  + IL 1 
Degenerative
cascade
Hydrolase, MMP, Collagenase secretion
Connective tissue degradation
MODEL FOR TISSUE DESTRUCTION IN
DIABETES MELLITUS “AGE MEDIATED”

20. MECHANISM OF DIABETIC INFLUENCE ON PERIODONTITIS
 Changes in subgingival microbiota?
 GCF glucose level = decreased chemotaxis of PDL fibers to PDGF
so decreased wound healing
 Peripheral vasculature = increased thickness of gingival
capillaries which impairs oxygen diffusion.
 Formation of ADVANCED GLYCATION END PRODUCTS
 Altered host immune response is important in pathogenesis
(defects in PMN adherence ,chemotaxis,phagocytosis)

21. Effect on periodontal flora:
 In the diabetic patient, the abnormal host defence mechanism in addition to
hyperglycemia state can lead to the growth of particular fastidious organism.
 The most frequently isolated microrganism are Prevotella intermedia followed
Camphylobacter rectus.
 The association of AAC & capnocytophaga is similar to periodontitis in healthy
patient & periodontitis in diabetic patient.

22. Effect on periodontal flora:
Mushimo et al 1987……differences in the subgingival bacterial flora in
people with diabetes, known to consists of Capnocytophaga,Vibrios
&Actinomyces,/ P ging,P intermedia,AAcomitans
.

23. Gingival crevicular fluid glucose level
 Increased blood glucose levels in diabetes are reflected in increased levels of
GCF glucose.
 In vitro studies it shows decreased chemotaxis of periodontal ligament
fibroblast to PDGF when placed in hyperglycemic environment compared to
normoglycemic condition.
 Thus, elevated glucose levels in diabetes adversely affect periodontal wound
healing & local host respose to microbial challenge.
 Levin et al 1989….increased GCF glucose…..alter periodontal wound
healing….altering interaction between cells and their extracellular matrix
within the periodontium.


24. PERIODONTAL VASCULATURE
 Increased thickening of gingival capillary endothelial basement
membrane & the walls of small blood vessels seen in diabetes.
 This thickening may impair oxygen diffusion& nutrient
provision across the basement membrane.
 Increased thickness of small vessel wall results in narrowing of
the lumen, altering normal periodontal tissue homeostasis.

25. Altered host response
 Alter host response has long been considered in the pathogenesis of
periodontitis.
 Defects in polymorphonuclear leucocyte adherence, chemotaxis,
phagocytosis have been observed in some individuals with diabetes.
 Altered neutrophil chemotaxis may contribute to severity of
periodontitis.these defects in diabetes may relate to insulin
dysregulation.

26.  Cells…..hyperresponsive to bacterial antigens…. increased
production of pro-inflammatory cytokines.
 Lin 2000…In response to endotoxin from P. gingivalis, monocytes
from patients with diabetes produce up to 32 times greater levels
of TNF- compared with monocytes from individuals without
diabetes.

27.  Impaired Neutrophil Function
 Diabetes…… impaired polymorphonuclear leukocyte adherence,
chemotaxis and phagocytosis….decrease bacterial killing,….
proliferation of pathogenic bacteria and increased periodontal
destruction.(Gillman et al 1978)

28.  Studies have shown hyper responsive monocyte
/macrophage phenotype in which stimulation by bacterial
antigens such as lipopolysaccherides (LPS) results in increased
proinflammatory cytokine production like TNFά , PGE2 , IL 1β .
 Accumulation of AGE in the periodontium causes influx of
monocytes . Once in the tissue AGEs interact with the receptor
RAGE induces proinflammatory cytokine production

29. COLLAGEN DEFECTS
 Collagen is the primary constituent of gingival ct and organic matrix of
alveolar bone .
 Changes in collagen metabolism contribute to alterations in wound healing
& to periodontal disease initiation and progression.
 MMPs are enzymes which are responsible for the break down of bone and
connective tissue during periodontal disease.
 These are produced by various cytokines , growth factors , PMNs, fibroblasts,
macrophages, endothelial cells, osteoblasts, osteoclasts .

30.  Activation of this collagenases activity has been observed in diabetic pts,which
degrade newly formed collagen macro molecules.
 In sustained hyperglycemic condition AGEs are also modifies the existing
collagen by cross linking .
 The net effect is alterations in collagen metabolism is a rapid degradation of
recently synthesized collagen by host collagenases and by AGEs .
 These changes in collagen metabolism result in altered wound healing .

31.  Langer 1999….Production of matrix metalloproteinases, such as collagenase,
increases in diabetics…..degrades the newly formed collagen that is critical to
healing of the periodontium.
 At the same time, AGE links to existing collagen decreases its solubility.
 Net result…..rapid dissolution of recently synthesized collagen and accumulation
of older collagen is susceptible to breakdown .

32.  Recent investigations reveal that AGEs can also form in response to any inflammatory
conditions (Anderson 1999)
 AGEs…….alteration of normal cellular composition and structure.
 Alters……function of ECM components, matrix-matrix interactions and cell-matrix
interactions.
 Affect the collagen stability and vascular integrity.
Effect of AGEs

33. RAGE
 Binding sites for AGEs
 Consists of a 332 amino acid region containing a “V” type domain and two “C”
domains followed by hydrophobic transmembrane and finally a highly charged
cytosolic tail of 42 amino acids, essential for signal transduction.

34. EFFECTS OF AGE-RAGE INTERACTION
 Endothelial cells:
 Causes cellular disturbances
 More the AGEs the higher is the RAGE.
 Binding of the AGE-RAGE lead to the development of vascular lesions.
 Increased permeability of the endothelial lining

35.  Mononuclear Phagocytes:
 Binding of AGEs to the RAGEs on macrophage….increased
chemotaxis.
 It also causes its activation resulting in increased release of TNF-α
EFFECTS OF AGE-RAGE INTERACTION

36.  Smooth Muscle Cells
Fibroblasts:
AGE-RAGE binding …… leads to reduced production of Type I
collagen
EFFECTS OF AGE-RAGE INTERACTION

38.  One plausible biologic mechanism why diabetics have more severe periodontal
disease is that glucose-mediated AGE accumulation would affect migration and
phagocytic activity of mononuclear and polymorphonuclear phagocytic cells,
resulting in the establishment of a more pathogenic subgingival flora.
 The maturation and gradual transformation of the subgingival microflora into
an essentially Gram-negative flora will in turn constitute, via the ulcerated pocket
epithelium, a chronic source of systemic challenge. This, in turn, triggers both an
"infection-mediated" pathway of cytokine upregulation, especially with secretion
of TNF-α and IL-1, and a state of insulin resistance, affecting glucose-utilizing
pathways.

39.  Hence, periodontal infection-mediated cytokine synthesis and secretion
may amplify the magnitude of the AGE-mediated cytokine response and
vice versa. In doing so, and in a manner similar to other bacterial
infections, the relationship between diabetes mellitus and periodontal
disease/infection becomes two way.

40. Periodontal Pathogen
Endotoxin, toxins cell
membrane products
Insulin
resistance
Hyperglycemia
Macrophage
AGE-Receptor
AGE-Protein
Proinflammatory cascade Synthesis + Secretion
TNF- + IL-1
Secretion TNF –  + IL-1  Degradative cascade
Connective tissue
destruction Bone
resorption
Hydrolase, MMP,
collagenase
secretion
Connective tissue
degradation
PERIODONTAL DISEASE DIABETES MELLITUS
PROPOSED MODEL FOR 2-WAY RELATIONSHIP BETWEEN
PERIODONTAL DISEASE AND DIABETES MELLITUS

41.  In the proposed model, a self-feeding two-way system of catabolic
response and tissue destruction ensues, resulting in more severe
periodontal disease and increased difficulty in controlling blood sugar.
 This proposed dual mechanism of tissue destruction suggests that control
of periodontal infection is essential to achieve long-term control of
diabetes mellitus.(Grossi SG, Genco RJ. 1998)

42.  Prevention of Diabetes:
 As little is known on the exact mechanism by which type 1 diabetes develops,
there are no preventive measures available for that form of diabetes. Some studies
have attributed a protective effect of breastfeeding on the development of type 1
diabetes.
 Type 2 diabetes risk can be reduced in many cases by making changes in
diet and increasing physical activity. A review article by the American Diabetes
Association recommends maintaining a healthy weight, getting at least 2½ hours of
exercise per week (marathon intensity or duration is not needed; a brisk sustained
walk appears sufficient at present), not over much fat intake, and eating a good
amount of fiber and whole grains.

43.  Although they do not recommend alcohol consumption as a preventative, they
note that moderate alcohol intake (at or below one ounce of alcohol per day
depending on body mass) may reduce the risk. They state that there is not
enough consistent evidence that eating foods of low glycemic index is helpful,
but nutritious, low glycemic-index (low carbohydrate) foods are encouraged. (It
should be noted that many low-GI foods are not recommended, for various
reasons.)
 Some studies have shown delayed progression to diabetes in predisposed
patients through the use of metformin, rosiglitazone, or valsartan. Breastfeeding
might also be correlated with the prevention of type 2 of the disease in mothers.

44. MEDICAL MANAGEMENT OF DIABETES
Prime treatment of diabetic patient is with consultant diabetologist.
1. Educate the patient
2. Diet
a. Obese pt – weight reducing diet, restrict calorie
content
b. Ideal body weight – maintenance diet
Carbohydrates - 55 – 65%
Proteins - 10 – 15%
Fat - 20 – 30%

45.  Low carbohydrate, sugar-free, low cholesterol vegetarian diet

To avoid potatoes, rice, sugar and sugar products

Salads of leafy green vegetables and lightly boiled vegetables should be
preferred

Spices, oil and ghee should be consumed in minimum quantity

46. 3. Exercise - Aerobic exercise
- Walking, swimming, cycling
- Brisk walking – 30mins for 5 days / week
- Evaluate CVS status before advising exercise
4. Therapy
Type 1 (IDDM) - Insulin
- Combination of long acting and short acting insulin
- Twice daily

47. Type 2 (NIDDM) – Not controlled with diet and exercise require oral
hypoglycemic drugs.
1. Biguanides – Metformin 500mg thrice daily after food
maximum dose 3g/day.
2. Biguanides can be combined with sulfonyl urea agents
Ex. Gllypenclamide, glypizide, should be given 15-30mts before food.
3. Alpha glucosidase inhibitors (A – carbose)
Interferes with absorption of disaccharides

52. Cure to Diabetes Using Stem Cells(December 2nd, 2006)
Dr. Ken Cho has discovered over 50 genes in mouse embryonic stem cells that
promote insulin-producing cells. If he is able to activate
these genes in mice, he’s one step closer to finding out how to
activate them in humans.
Activating these cells will mean that a diabetic person’s life-style
can go back to normal with their cells producing insulin for them.

54.  Scientists have conducted a risky trial and successfully injected
stem cells into 15 patients with type 1 diabetes. Thirteen of the 15
patients have been able to live healthy lives ever since the
treatment!
Diabetes Successfully Cured Through Stem
Cells(April 11th, 2007 )

55. DENTAL MANAGEMENT OF DIABETIC PTs
 Pts who present to the dental office with intraoral findings
suggestive of a previously undiagnosed diabetic condition should be
questioned clearly.
 Questions should be targeted towards eliciting a clear history of
polyuria , polydypsia , polyphagia
 If clinician suspects undiagnosed diabetes should send for lab
evaluation & physician refferal is indicated .

56.  Well controlled diabetic patient with periodontitis have positive response to nonsurgical therapy,
periodontal surgery and maintenance that are similar to those of people without diabetes
 Other key dental treatment consideration for diabetic patients include stress reduction, treatment
setting, the use of antibiotics diet modifications, appointment timing, changes in medication
regimens and the management of emergencies.
 Some clinicians prefer to prescribe prophylatic antibiotic coverage prior to surgical therapy if the
diabetic patient’s glycemic control is poor. This usually applies to emergency situations since
elective procedures are generally deferred until glycemic control improves. In patients with severe
peridontitis, adjunctive use of tetracycline antibiotics in conjunction with the mechanical
periodontal therapy may have beneficial effects on glycemic control as well as on periodontal
status.

57. Before dental treatment begun, the patient may check his or her blood glucose. If the level
is near the lower end of the normal range, a small amount of pre treatment carbohydrate
may prevent hypoglycemia during the appointment. Having the glucometer available also
allows rapid determination of blood glucose, levels when the patient experience signs and
symptoms of hypoglycemia.
 Because diet is a major component of diabetes management, diet alterations that
are made because of dental treatment may have a major impact on the patient.

58. DIABETIC PTs WITH PERIODONTITIS
 The well controlled diabetic pts with periodontal disease is an acceptable
candidate for complete periodontal therapy.
1) Periodontal surgery should be scheduled in the morning
2) Treatment should be as a traumatic as possible.
3) Should not interfere with normal pts dietary intake.
4) pts anxiety should be managed to minimize endogenous epinephrine
release.

59. Appointment timing for the diabetic patient in often determined by the
individual’s medication regimen Peak action of insulin abnormalities to decide
about appointment
Insulin – greatest risk of hypoglycemia will occur about 30 – 90 min
after injection
Lispro insulin – 2 to 3 hrs
Lente insulin – 4 to 10 hrs
Metformin & thiazolidinedione – rarely cause hypoglycemia
The greatest risk would occur in a patient who has taken the usual amount of
insulin or oral agent but has reduced or eliminated a meal prior to dental
treatment .
HYPOGLYCEMIA?HYPERGLYCEMIA?
BECAUSE HYPERGLYCEMIC EMERGENCIES DEVELOP MORE SLOWLY THAN
DOES HYPOGLYCEMIA ,THEY ARE LESS LIKELY TO BE ENCOUNTERED IN
DENTAL OFFICE.

60.  Periodontal treatment are designed to decrease the bacterial challenge
& reduce inflammation might restore insulin sensitivity over
time,resulting in improved metabolic control
There is little evidence regarding the success/failure of dental implant
therapy in diabetic individuals
Diabetic is often considered a reletive contraindications to implant
placement but in well controlled diabetes there is no reason to avoid
implant therapy.
Patients with poorly controlled diabetes may not repond well to any
surgical treatment including implant placement due to impaired wound
healing

61. Management of diabetic emergencies
Hypoglycemia
 Causes of hypoglycemia
injection of excess insulin, delaying or skipping of meals, increasing
of exercise, stress.
 Signs & symptoms
confusion, shakiness, , dizziness, tachycardia, seizures, loss of
consciousness.
 Rapid onset --  adrenalin release --- anxiety, irritation and
disorientation--- even may lead to convulsion
 (Strong bounding pulse – sweaty skin)

62. Emergency treatment of
hypoglycemia
 In awake pt, give 15g of carbohydrate orally,in the form of 120-180ml
fruit juice or sugared soda, 3-4 tsp table sugar
 If pt unable to use oral route &IV is in place, administer
25-30 ml 50% dextrose or 1 mg glucagon IV.
 If pt unable to use oral route & IV is not in place, administer 1 mg
glucagon subcutaneousely & intramuscularly.
 Moniter pt for 1 hour after recovery & seek emergency medical
assitance if pt does not respond.

63. HYPERGLYCAEMIA
 If Collapse due to hyperglycaemia ( Diabetic
ketoacidosis ) because of relative / absolute deficiency of
insulin
 Signs:
 Dehydration (dry skin, weak pulse, hypotension)
 Acidosis (Deep breathing)
 Ketosis (Acetone smell on breathing, vomiting)

64. MANAGEMENT
 If collapse due to hyperglycaemia:
 Establish IV line
 Start Rapid rehydration ( Blood for baseline need of
glucose, electrolyte, pH)
 Insulin started 20Units IM stat then 6 units hourly
as an infusion
 To correct dehydration – concentrate more on K+
electrolyte loss

65. CONCLUSION:
Diabetes mellitus is a common medical disorder that will be encountered
by every practicing dentist. Knowledge by the dentist of the general and
oral signs and symptoms of undiagnosed or poorly controlled diabetes
mellitus are essential, and patients displaying these signs or symptoms
should receive medical referral
In the event the degree of control of a known diabetic is unknown or the
patient is poorly controlled, antibiotic therapy should be administrated in
conjunction with any necessary surgical procedure or in the presence of
oral infection.

66. CONCLUSION:
The practitioner must be prepared to manage diabetic emergencies if they
occur in the dental office, and hypoglycemic incidents are most likely.
. New evidence suggests that advanced periodontal disease may interfere with
diabetes mellitus control and the physician should be made aware of the
patient’s periodontal status. Under most circumstances, the well-controlled
diabetes mellitus patient can receive safe and effective periodontal therapy
with some modification of office protocol.

67. Thank you all…….