Dr. Shweta Sarate- Post graduate Dept. of Periodontology

1. History
1500 BC – Egyptian physician Hesy-Ra “ Ebers
Papyrus” Earliest known record of diabetes.
250 BC – Greek physician Arateus defined diabetes as
‘the softening down of limbs and flesh into urine.’
He described the term “ Diabetes” from greek word
“ Diabaino” which means siphon or water pipe
1604 A.D
There was a big mistake done in diagnosing diabetes by
the physician ‘Galen of Pergamum’ who diagnosed this
disease as a disorder of the kidneys.
1

2. 2
11 th Century
Diabetes was diagnosed by ‘water tasters’ and people’s urine suffering from
diabetes was checked by drinking it and on testing it was found sweet in taste.
As a result the word ‘mellitus’ was added with diabetes.
16 th Century
In the 16 th century, diabetes was identified as a severe general disorder by
the Paracelsus.
1870s
French physician named as Bouchardat treated diabetes with balanced diet
1870- German Student Paul Langerhans discovers Islet cells of pancreas but
unable to describe its function

3. The greatest discovery concerning the treatment
of diabetes occurred in July of 1921, when two
Canadian investigators, Frederick Banting and
Charles Best, from the University of Toronto,
were able to extract insulin from the pancreas of
one dog and inject it into another dog that they
had made diabetic by removing from his pancreas.
This experiment proved that indeed insulin
controlled the sugar of the diabetic dog!
1777 – Rosalyn Yallow awarded Nobel Prize for
precise measurement of Insulin.
1923 – Banting & Macleod awarded Nobel prize.

4. “The World
and
Diabetes
4

5. ▪ 246 million people.
▪ 380 million in 2025.
▪ Increases by 7 million each year.
▪ Every 10 seconds a person dies from diabetes-related causes.
▪ Every 10 seconds two people develop diabetes.
▪ Fourth leading cause of global death by disease.
▪ At least 50% of all people with diabetes are unaware of their
condition.
▪ Type 2 diabetics will die 5-10 years before people without diabetes,
mostly due to cardiovascular disease.
▪ (International Diabetic Foundation, 2016)
5

6. India and
Diabetes
6

7. ▪ 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 risk of DM through inheritance.
▪ 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, 2016)

8. Introduction
8

9. ▪ Diabetes is a chronic clinical syndrome characterised
by hyperglycemia due to deficiency or defective
response to insulin.
▪ Heterogenous group of disorders –hyperglycemia as a
common feature.
▪ Chronic disorder of carbohydrate ,fat , protein
metabolism.
▪ -Davidson’s Principles and
Practice of Medicine
9

10. Classification
1. Type 1 diabetes ( cell destruction, leads to absolute insulin deficiency)
· Immune mediated
· Idiopathic
2. Type 2 diabetes (insulin resistance with relative insulin deficiency).
3. Genetic defects of  cell function.
- Maturity onset diabetes of the young (MODY), caused by mutations in ;
- Hepatocyte nuclear factor 4 (HNF – 4) (MODY3).
- Glucokinase (MODY2).
- Hepatocyte nuclear factor 1 (HNF - 1) (MODY5).
- Insulin promoter factor 1 (HNF - 1) (MODY5).
- Hepatocyte nuclear factor 1 (HNF- 1) (MODY5)
- Neurogenic differentiation factor 1 (Neuro D1) (MODY6).
- Mitochondrial DNA mutations.
10

11. 4. Genetic defects in insulin processing or insulin action
· Defects in proinsulin conversion.
· Insulin gene mutations.
· Insulin receptor mutations.
5. Exocrine pancreatic defects.
· Chronic pancreatitis
· Pancreatectomy
· Neoplasia
· Cystic fibrosis
· Hemachromatosis
· Fibrocalculous pancreatopathy.
11

12. 6. Endocrinopathies
· Acromegaly
· Cushing syndrome
· Hyperthyroidism
· Pheochromocytoma
· Glucagonoma.
7. Infections
· Cytomegalovirus
· Coxackie virus B.
12

13. 8. Drugs
· Glucocorticoids
· Thyroid hormone
·  - interferon
· protease inhibitors
·  - adrenergic agonists
· Thiazides
· Nicotinic acid
· Phenytoin.
9. Genetic syndromes associated with diabetes
· Down syndrome
· Kleinfelter syndrome
· Turner syndrome.
10.Gestational diabetes mellitus
- Davidson’s Principles and Practice of Medicine
13

14. Epidemiology
 The most recent data from the International Diabetes Federation
indicated that an estimated 415 million adults aged 20–79 years
worldwide have DM in 2015 and the number will project to 642
million in 2040, with the prevalence increasing from 8.8 to 10.4%.
Despite the high prevalence of diagnosed DM, as many as 193
million people representing close to half of all people with DM are
unaware of their disease.
14

15.  Regionally, the age-adjusted prevalence of DM
is 3.8% in Africa, 7.3% in Europe, 10.7% in
Middle East and North Africa, 11.5% in North
America and Caribbean, 9.6% in South and
Central America, 9.1% in Southeast Asia, and
8.8% in Western Pacific. China, India, and the
USA remain the top three countries with the
largest number of people with DM.
15
Fan W. Epidemiology in diabetes mellitus and cardiovascular disease.
Cardiovascular Endocrinology & Metabolism. 2017 Mar 1;6(1):8-16.

16. DIAGNOSIS

17. ▪ Blood glucose values are normally maintained in a very
narrow range, usually 70 to 120 mg / dl. The diagnosis of
diabetes is established by noting elevation of blood
glucose by any one of three criteria.
1.A random glucose > 200 mg / dl, with classical signs and
symptoms .
2.A fasting glucose > 126 mg / dl on more than one occasion.
3. An abnormal oral glucose tolerance test (OGTT) in which
the glucose is > 200 mg /dl 2 hours after a standard
carbohydrate load.
17

18.  Individuals with fasting glucoses more than 110 mg / dl or less
than 140 mg / dl following an OGTT are considered to be
euglycemic.
 However those with fasting glucose greater than 110 but less
than 126 or OGTT values greater than 140 but less than 200
are considered to have impaired glucose tolerance (IGT).
Individuals with IGT have a significant risk of progressing to
overt diabetes over time. In addition those with IGT are at risk
for cardiovascular disease due to the abnormal carbohydrate
metabolism as well as the coexistence of other risk factors
such as low HDL, hypertriglyceridemia and increased
plasminogen activator( PAI – 1).
18

19.  Revised criteria for diagnosis emphasize FBS as a r
eliable & convenient test
 Random 200 mg/dl with classic symptoms
( polyuria,polydipsia&wt loss) is sufficient for diagnosis.
▪ Davidson’s Principles and Practice of Medicine
19

20. PATHOPHYSIOLOGY

22. ▪ The endocrine pancreas consists of about 1million microscopic
clusters of cells, the islets of Langerhans.
▪ The first evidence of islet formation in the human fetus is seen at
9 to 11 weeks.
▪ In aggregate, the islets in the adult human weigh only 1 to 1.5
gm, individually, most islets measure 100 to 200 m and consists
of four major and two minor cell types.
22

23. ▪ The four major types are , ,  and PP (pancreatic polypeptide)
cells and the two minor types are D1 and enterochromaffin cells.
▪ The major types make up about 68%, 20%, 10% and 2% respectively,
of the adult islet cell population. They can be differentiated
morphologically by their staining properties, by the ultra structural
characteristics of their granules, and by their hormone content.
▪ The  cell produces insulin. The insulin – containing intracellular
granules contain a crystalline matrix with a rectangular profile,
surrounded by a halo.
▪ The  cell produces Glucagon and the granules are found with
closely applied membranes and dense center
23

24. ▪  cells contain Somatostatin, which suppresses both insulin and
glucagon release ; they have large, pale granules with closely applied
membranes.
▪ PP cells contain a unique pancreatic polypeptide that exerts a
number of gastrointestinal effects, such as stimulation of secretion
of gastric and intestinal enzymes and inhibition of intestinal
motility. These cells have small, dark granules and not only are
present in islets, but also are scattered in the exocrine pancreas.
▪ The minor cell type D1 cell elaborate vasoactive intestinal
polypeptide (VIP), a hormone that induces glycogenolysis and
hyperglycemia ; it also stimulates gastrointestinal fluid secretion and
causes secretory diarrhoea and Enterochromaffin cells synthesize
serotonin and are the source of pancreatic tumors that causes the
carcinoid syndrome.
24

25. 25

26. Synthesis of Insulin
26

27. Physiologic role of insulin
foods
broken down into glucose
the circulatory system
used by tissue cells for energy and growth.
27
Most cells require the presence of
insulin to allow glucose entry
excluding those in the brain and
central nervous system

28. 28
insulin secretion
occurs
glucose
concentrations
glucose is able to exit
the
bloodstream
and enter the tissues
resulting in its utilization
by the cells and thus
decreased
blood glucose
concentrations

29. 29
insulin secretion
occurs
glucose
concentrations
HYPERGLYCEMIA
insulin secretion
occurs HYPOGLYCEMIA

30. 30
excess glucose
stored in the liver
in the form of glycogen
fasting state
glucose demand exceeds
glucose available
from recent
food consumption
•liver breaks down
•glycogen
By process of glycogenolysis.
•releases glucose into the
•bloodstream
liver also produces glucose
Non-carbohydrate sources such as
amino acids and fatty acids
through the process of
gluconeogenesis

31. Role of Insulin
31

32. RAPID [ SEC ]
INCREASED TRANSPORT OF GLUCOSE ,
AMINOACIDS & K+
INTERMEDIATE [ MIN]
STIMULATION OF PROTEIN SYNTHESIS
INHIBITION OF PROTEIN DEGRADATION
ACTIVATION OF GLYCOLYTIC ENZYMES &
GLYCOGEN SYNTHASE.
INHIBITION OF PHOSPHORYLASE &
GLUCONEOGENIC ENZYMES.
DELAYED [ HRS]
INCREASE IN mRNAs FOR LIPOGENIC & OTHER
ENZYMES.
32

33. Effect of Insulin
33

34. Signs and Symptoms of Diabetes
▪ Polyphagia
▪ Polydypsia
▪ Polyurea
▪ Blurry vision
▪ Dark rough patch of skin
▪ Dry mouth
▪ Excessively dry skin
▪ Fatigue
▪ Unexplained loss of weight
▪ Tingling or pain in feet or legs
▪ Wounds that do not heal quickly
▪ Sexual dysfunction
34

35. Type 1 Diabetes
▪ Occurs at young age; can also occur in later life
▪ Most frequent chronic disease in children
▪ Cell mediated auto immune disorder
▪ Destruction of β cells of pancreas
▪ Destruction rate is variable
▪ Multiple genetic predisposition
▪ Linked to the presence of Human Leukocyte Antigens
(HLA)
▪ Environmental factors (Viral infections)also play a role
35

36. 36

37. 37

38. T-cells in Type 1 Diabetes
▪ Autoreactive T helper 1 (Th1) cells play important role
▪ T-cells exhibit direct cytotoxicity via 3 mechanisms
▫ The cellular protein perforin
▫ Stimulates apoptosis
▫ Producing toxic cytokines.
▪ The pro-inflammatory cytokines in Type 1 diabetes are
▫ interleukin-1β (IL-1β)
▫ Tumor necrosis factor-α (TNF-α)
▫ Interferon-γ (IFN-γ)
▪ IFNγ and IL-2, are believed to cause islet inflammation
(insulitis) and ß cell destruction .
38

39. 39

40. Diabetic Ketoacidosis
40

41. Type 2 Diabetes
▪ 90 % of all diabetic cases
▪ Stronger genetic component
▪ Type 2 may remain undiagnosed for years!
▪ Characteristic abnormalities
▫ Peripheral resistance to insulin
▫ Impaired pancreatic insulin secretion
▫ Increased glucose production in liver
▪ Pancreas continues to produce insulin
▪ Obesity – major risk factor
▪ Only oral hypoglycemics is suffice.
▪ Insulin may also be used in some patients
▪ Keto acidosis not common in Type 2 patients except in stress
41

42. 42

43. Differences
43

44. Syndrome X- Metabolic Syndrome
▪ Metabolic syndrome X is a multifaceted syndrome, which
occurs frequently in the general population.
▪ It is more common in men than in women. A large segment
of the adult population of industrialized countries develops
the metabolic syndrome, produced by genetic, hormonal
and lifestyle factors such as obesity, physical inactivity and
certain nutrient excesses.
44

45. ▪ This disease is characterized by the clustering of insulin
resistance and hyperinsulinemia, and is often associated
with dyslipidemia (atherogenic plasma lipid profile),
essential hypertension, abdominal (visceral) obesity,
glucose intolerance or noninsulin-dependent diabetes
mellitus and an increased risk of cardiovascular events.
Abnormalities of blood coagulation (higher plasminogen
activator inhibitor type 1 and fibrinogen levels),
hyperuricemia and microalbuminuria have also been
found in metabolic syndrome X.
▪ - Timar O, Sestier F, Levy E. Metabolic syndrome X: a review. The Canadian journal of
cardiology. 2000 Jun;16(6):779-89.
45

46. 46

47. Impaired Glucose Tolerence &
Impaired Fasting Glucose
▪ Implies a metabolic state between normal
glycemia and diabetes
▪ Also termed as Prediabetes
▪ IGT – hyperglycemia only after large glucose load.
▪ IFG – Elevated fasting glucose, but normal in fed
state
▪ Both are primarily risk factors for future Diabetes
47

48. Brittle Diabetes
▪ Uncontrolled type 1 diabetes ( <1% of Type 1)
▪ People with brittle diabetes frequently
experience large swings in blood glucose levels.
▪ More common in young women
▪ Brittle diabetes can be caused by
▫ Gastrointestinal absorption problems
▫ Drug interactions
▫ Defects in insulin absorption
▫ Hormonal malfunction.
48

49. Gestational Diabetes
▪ Usually in 3rd trimester of pregnancy
▪ Overweight women
▪ >25 years age
▪ Family history of diabetes
▪ Increases perinatal morbidity and mortality
▪ After 6 weeks of parturition, reclassification
is done.
▪ Most women become normoglycemic
▪ 30-50% develops Type 2 diabetes within 10
years
49

50. Pathophysiology of Diabetes
50

51. Diagnosis

52. Fasting Plasma Glucose
52

53. Oral Glucose Tolerance Test
(OGTT)
53

54. Glycoselated Hemoglobin (HbA1c)
▪ HbA1c is a test that measures the amount
of glycated hemoglobin in your blood.
Glycated hemoglobin is a substance in red
blood cells that is formed when blood
sugar (glucose) attaches to hemoglobin.
54

55. 55

56. Urinalysis
▪ • Glycosuria
▪ • Ketone bodies
56

57. Diagnostic Criteria
▪ • Classic signs of HYPERGLYSEMIA with
▪ CPG ≥200mg/dL
▪ • OGTT ≥200mg/dL
▪ • FPG ≥126mg/dL
▪ • A1C ≥ 6.5%
57

58. Glycated Hemoglobin Assay(HbA1c)
58
4-6% Normal
<7% Good diabetes control
7-8% Moderate diabetes control
>8% Action suggested to
improve diabetes control
-Periodontal Medicine ,2000

59. Diabetes
Mellitus
Chhattisgarh Dental College & Research Institute, Rajnandgaon
Seminar Presentation on
Department of Periodontics
Guided by:
Dr. Sushma Das
Dr. Padmakanth Mannava
Dr. Pooja Walia
Dr. Lubna Siddiqui
Presented by:
Dr. Shweta Sarate
PG Part II

60. Contents
Contents
Origin and history
Introduction
Classification
Epidemiology
Role of insulin
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
60

61. Impaired Glucose Tolerance/Impaired Fasting Glucose
Gestational Diabetes
Clinical presentation
Diagnosis of diabetes
Classic complications of diabetes
Oral diseases and diabetes
Mechanisms of Diabetic Influence on Periodontium
Effects of periodontal infection on glycemic control of diabetes
Management of the diabetic patient
Management of Diabetic Emergencies
Conclusion
References
61

62. Advanced Glycation
End Products

63. Advanced Glycation End Product
 Hyperglycaemia has both acute and chronic effects.
 An important chronic effect involves the irreversible
nonenzymatic glycation of proteins and lipids leading to
the formation of AGEs.
 AGEs can lead to cellular stress by exerting pro-
inflammatory/oxidant effects directly, or through
interaction with cell-surface receptors.
 Expression of AGEs, along with markers of oxidant stress,
in gingival tissues of diabetic patients with periodontitis
has been significant.
▪ Schmidt AM, Weidman E, Lalla E, Du Yan S, Hori O, Cao R, Brett JG, Lamster IB. Advanced glycation endproducts (AGEs) induce oxidant stress in the
gingiva: a potential mechanism underlying accelerated periodontal disease associated with diabetes. Journal of periodontal research. 1996 Oct
1;31(7):508-15.
63

64. ▪ Upon exposure of proteins/lipids to reducing sugars, the process of non-
enzymatic glycation and oxidation of these structures is initiated. The
early,reversible products k/a Schiff bases/Amadori products, the best known
of which is glycosylated hemoglobin. After a series of further complex
rearrangements, the irreversibly formed AGEs result. AGEs accumulate in
diabetic tissue and plasma in normal aging, but to an accelerated degree in
diabetes. They are linked to the development of diabetic complications
64

65. EFFECTS OF AGE’S
▪ Advanced glycation end product forms on collagen.
▪ AGE
▪ Increased collagen crosslinking
Highly Stable collagen macromolecules
Accumulation of Proetins on affected site.
65

66. In blood vessels
▪ Age modified collagen accumulates
▪ Thickens the blood vessel wall and narrows lumen
▪ In addition, circulating LDLin vessel lumen is immobalised in presence of AGE modified
collagen
▪ Hence, hyperglycemia contributes to formation of increasing levels of AGE modifies
collagen.
▪ Circulating LDL cross-links with AGE modified collagen and leads to formation of
ATHEROMA in diabetic macrovasculature.
▪ Periodontal Medicine ,2000
66
I

67. ▪ AGE proteins were found in saliva of diabetic
patients and were linked to dental plaque levels
and AGE levels in serum were shown to be
significantly associated with the extent of
periodontitis in type 2 individuals (Takeda et al.
2006).
▪ Takeda M, Ojima M, Yoshioka H, Inaba H, Kogo M, Shizukuishi S, Nomura M, Amano A. Relationship of
serum advanced glycation end products with deterioration of periodontitis in type 2 diabetes patients.
Journal of periodontology. 2006 Jan 1;77(1):15-20.
▪ RAGE is a multiligand signalling receptor and
member of the immunoglobulin superfamily of
cell-surface molecules.
67

68.  RAGE expression is increased in diabetes and its
activation through ligand interaction has an established
role in the development and progression of other
diabetic complications.
 The AGE-RAGE interaction on monocytes increases
cellular oxidant stress and activates the transcription
factor (NF-kB), which alters the phenotype of the
monocyte/macrophage and results in the increased
production of proinflammatory cytokines such as IL-1b
and TNF-a.
68

69. ▪ Influence of AGEs and RAGE on diabetic periodontium. This figure
summarizes the hypotheses regarding potential role of enhanced AGE
interaction with cellular RAGE in the pathogenesis of diabetes-
associated periodontal disease.
69

70. 70
When body proteins are exposed to a high concentration of glucose for a long time in
vivo, they are non-enzymatically glycated and structurally modified termed advanced glycation end
products (AGE). Monocytes are chemotactic to AGE and take up this protein via specific receptors termed
RAGE or MSR. Monocytes thus activated produce oxygen-free radicals that are destructive to tissues and
proinflammatory cytokines, which further exaggerate inflammatory tissue destruction.

71. Complications of
Diabetes

72. Acute Complications
Very Insufficient Insulin
Severe
Osmotic
Dehydration
Marked
Hyperglycemia
GLYCOSURIA
LYPOLYSIS CELLULAR
HUNGER
OSMOTIC DIURESIS WEIGHT LOSS POLYPHAGIA
POLYURIA
POLYDIPSIA

73. CHRONIC COMPLICATIONS OF DIABETES
MILLETUS
▪ • NEPHROPATHY – DAMAGE & OBLITERATION OF CAPILLARIES SUPPLYING THE
KIDNEY
▪ • HEART DISEASE – MI FROM ATHEROSCLEROSIS
▪ • SKIN CHANGES – DIABETIC DERMOPATHY – HYPERPIGMENTED & SCALY
▪ PRETIBIAL AREAS (Acanthosis Nigricans)
▪ • LIVER CHANGES – ENLARGEMENT & FATTY INFILTRATION
73

74. CLASSIC COMPLICATIONS OF DIABETES
MELLITUS
▪ RETIOPATHY
-Blindness
▪ NEPHROPATHY
-Renal Failure
▪ NEUROPATHY
-Sensory
-Autonomic
▪ MACROVASULAR DISEASE
-Peripheral , Cardiovascular,Cerebrovascular
▪ ALTERED WOUND HEALING
74

75. DAWN PHENOMENON
▪ • The "dawn effect," also called the "dawn phenomenon," is the
term used to describe an abnormal early-morning increase in
blood sugar (glucose) — usually between 2 a.m. and 8 a.m. in
people with diabetes.
▪ While we sleep, our body doesn’t need as much energy. But
when we are about to wake up, it gets ready to burn more fuel.
It tells our liver to start releasing more glucose into your blood.
That should trigger our body to release more insulin to handle
more blood sugar.
▪ Patients having diabetes, their body doesn’t make enough
insulin to do that. That leaves too much sugar in your blood, a
problem called hyperglycemia.
75

76. 76
Oral Diseases
and
Diabetes

77. Oral Manefestations 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 (TMD)
▫ Depapillation and fissuring of the tongue.
77

78. ▪ Salivary glands
▫ Xerostomia is common, but reason is unclear.
▫ Tenderness, pain and burning sensation of tongue.
▫ May secondary enlargement of parotid glands with
sialosis.
▪ Dental caries
▫ Increase caries prevalence in adult with diabetes.
(xerostomia, increase saliva glucose)
▫ Hyperglycemia state shown a positive association
with dental caries.
78

79. ▪ Cheilosis
▪ Alteration of flora of oral cavity – Predominance
of candida albicans
79

80. 80
Cracking of Oral Mucosa
Increased tooth sensitivity
Increased incidence of Enamel Hypoplasia

81. Oral Manifestations and
Complications
▪ 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
▫ Al-Maskari AY, Al-Maskari MY, Al-Sudairy S. Oral manifestations and complications of diabetes mellitus: a
review. Sultan Qaboos University Medical Journal. 2011 May;11(2):179.
81

82. Rosenberg CS. Wound healing in the patient with diabetes mellitus. The Nursing clinics of North America. 1990 Mar;25(1):247-61.
Delayed healing of wounds
▫ . Factors such as age, obesity, malnutrition, and macrovascular and
microvascular disease may contribute to wound infection and delayed wound
healing especially in the type II diabetic patient.
▫ In addition, hyperglycemia caused by decreased insulin availability and
increased resistance to insulin can affect the cellular response to tissue injury.
Immune cells necessary for wound healing, such as PMN leukocytes and
fibroblasts, as well as studies of injured tissue suggest that there is a delayed
response to injury and impaired functioning of immune cells in diabetes
mellitus.
▫ There is evidence that these impairments may be the result of both an
inherent (genetic) defect as well as decreased insulin availability and
increased blood glucose concentration.
82

83. 83
Diabetes
and Periodontal
Disease

84. 84
Both diabetes and periodontitis are chronic diseases. Diabetes has many
adverse effects on the periodontium, including decreased collagen turnover,
impaired neutrophil function, and increased periodontal destruction.
Diabetic complications result from microvascular and macrovascular
disturbances. With respect to the periodontal microflora, no appreciable
differences in the sites of periodontal disease have been found between
diabetic and non-diabetic subjects.
A great deal of attention has been directed to potential differences in the
immunomodulatory responses to bacteria between diabetic and non-diabetic
subjects. Neutrophil chemotaxis and phagocytic activities are compromised in
diabetic patients, which can lead to reduced bacterial killing and enhanced
periodontal destruction. Grover HS, Luthra S. Molecular mechanisms involved in the bidirectional relationship
between diabetes mellitus and periodontal disease. Journal of Indian Society of Periodontology. 2013 May;17(3):292.
Association between diabetes mellitus and periodontitis

85. Gingivitis
▪ Higher risk of developing gingivitis ( Jenkins et al 2001 Perio
2000)
▪ Theprevalence of gingivitis in children and adolescents is
nearlytwice when compared with non diabetics
(DePommereau et al 1998 JCP)
▪ “Diabetes mellitus- associated Gingivitis” – Specific entity in
the recent classification of gingival diseases
( Holmstrup et al 1999 Ann Periodontol, Issue 4)
▪ Several studies show a positive association
▪ Normalizing the glycemic levelsmay significantly reduce the
severity and extent of gingivitis in diabetics (Karjalainen et al
1996 J Dent Res )
85

86. Periodontitis
▪ GCF shows an increased glucose level
▪ Diabetic status increases the host susceptibility
to periodontal infection due to impaired
immune response. (Dranchman et al 1966,
Crook et al 1998)
▪ Increased calculus formation in patientswith
diabetes, may be due to an increased
concentration of serumcalcium in both parotid
and submandibular saliva
(Marder et al.1975 JOP)
86

87. Factors affecting Diabetic
Influence on Periodontium
▪ Sub gingival microbiota
▪ GCF Glucose levels
▪ Periodontal vasculature
▪ Host response
▪ Collagen metabolism
▪ Periodontal Medicine 2000
87

88. Subgingival Microbiota
▪ Early studies showed possible differences in subgingival
colonization
▪ Recent studies, however show very little differences.
▪ Periodontally diseased sites in diabetic patients harbor
similar species as comparable in non diabetic individuals.
( Christagu et al JCP 1998, Zambon et al JOP 1988, Sastrowijoto et al JCP
1989)
88

89. GCF Glucose Level
▪ Twice amount of glucose in GCF of diabetic patients
▪ Decreased chemotaxis of periodontal fibroblasts to PDGF in a
hyperglycemic environment.
▪ Thus, elevated GCF glucose levels may affect periodontal
wound healing and also host response to microbial challenge.
▪ Increased thickness of gingival capillary endothelial cell
basement membranes and walls of small blood vessels results
in narrowing of lumen,altering normal periodontal tissue
hemostasis.
89

90. Periodontal Vasculature
▪ Periodontal vasculature is also affected like other vessels.
▪ Basement membrane of the endothelial cells of gingival capillaries are
thickened
▪ Leads to impaired oxygen and nutrient supply
▪ Two fold increase in AGE in diabetic gingiva
▪ Increased oxidant stress in capillaries
▪ Leading to wide spread vascular injury
▪ (Frantzis et al. 1971 JOP, Listgarten et al.1974 JOP, Seppala et al.1997 JOP)
90

91. AGE and Periodontal Vasculature
▪ Act by
▫ Stimulation of arterial smooth muscle
proliferation
▫ AGE –modified collagen inhibits normal
degradation leading to thickness of
basement membrane
▫ AGE –modified collagen can bind circulating
LDL resulting in atheroma and further
narrowing.
▪ Thus results in increased severity and
progression of periodontitis.
91

92. AGE and its effect on PDL- A
HypothesisA
AGE – enriched Gingival tissue
Activation of
1.Endothelial RAGE - Permebility
Adhesion molecules
2. Macrophage RAGE – Cytokines
MMPS
3. Fibroblast RAGE – MMPS
Collagenase
Exaggerated response to periodontal pathogens
Accelerated destruction of non mineralized C.T and bone in diabetes
92

93. Collagenase Response
▪ Increased Collagenase activity
▪ Collagenases primarily degrade newly formed
collagen
▪ AGE-modified collagen predominates
▪ Net effect is destruction of newer collagen and
dominance of older, cross-linked collagen.
▪ Leading to impaired wound healing
93

94. Insulin Therapy & Periodontitis
94

95. 95

96. Periodontitis Influence on Diabetes
▪ Systemic inflammation plays a major role in insulin
sensitivity and glucose dynamics.
▪ Periodontal diseases can induce or perpetuate an
elevated systemic chronic inflammatory state
▫ Increased serum C-reactive protein,
▫ Increased interleukin-6,
▫ Increased fibrinogen levels
(D’Aituo 2004 JDR, Loos et al 2000 JOP)
▪ Periodontal infection may elevate the systemic
inflammatory state and exacerbate insulin resistance.
96

97. Two way Relationship

98. ▪ Exacerbated and dysregulated inflammatory responses are at the heart of the proposed two-way interaction between diabetes and
periodontitis (purple box), and the hyperglycaemic state results in various proinflammatory effects that impact on multiple body
systems, including the periodontal tissues. Adipokines produced by adipose tissue include proinflammatory mediators such as TNF-α,
IL-6 and leptin. The hyperglycaemic state results in deposition of AGEs in the periodontal tissues (as well as elsewhere in the body),
and binding of the receptor for AGE (RAGE) results in local cytokine release and altered inflammatory responses. Neutrophil function is
also altered in the diabetic state, resulting in enhancement of the respiratory burst and delayed apoptosis (leading to increased
periodontal tissue destruction). Local production of cytokines in the periodontal tissues may, in turn, affect glycaemic control through
systemic exposure and an impact on insulin signalling (dotted arrow). All of these factors combine to contribute to dysregulated
inflammatory responses that develop in the periodontal tissues in response to the chronic challenge by bacteria in the subgingival
biofilm, and which are further exacerbated by smoking.
98

99. Periodontitis & Glycemic
Control
▪ Mechanism of Obesity causing Insulin Resistance:
▪ Tumor necrosis factor-a, produced in abundance by adipocytes, increases
insulin resistance by preventing autophosphorylation of the insulin
receptor and inhibiting second messenger signaling via inhibition of the
enzyme tyrosine kinase .
▪ Interleukin-6 is important in stimulating tumor necrosis factor-a
production; thus, elevated interleukin-6 production in obesity results in
higher circulating levels of both interleukin-6 and tumor necrosis factor-a.
▪ Periodontal infection can induce elevated serum interleukin-6 and tumor
necrosis factor-a levels, and may play a similar role as obesity in inducing
or exacerbating insulin resistance.
99
Janket SJ, Wightman A, Baird AE, Van Dyke TE, Jones JA. Does periodontal treatment improve
glycemic control in diabetic patients? A meta-analysis of intervention studies. Journal of dental
research. 2005 Dec;84(12):1154-9.

100. 100
Diabetes and Dental Implants

101. Diabetes and Implant Considerations
▪ Diabetes induced bone changes
▫ Inhibition of collagen matrix formation
▫ Alterations in protein synthesis
▫ Increased time for mineralization of osteoid
▫ Reduced bone turn over
▫ Decreased number of osteoblasts and
osteoclasts
▫ Altered bone metabolism
▫ Reduction in osteocalcin production
101

102. Diabetic Disturbances in Implant Wound
Healing
102
Blood Clot
Formation
• Changes in wound healing Proteins
Bone Resorption
phase
• Decreased number of Osteoclasts
Matrix Formation
phase
• Inhibition of Collagen Formation
Bone Deposition
phase
• Decreased Osteoblasts
Maintanence of
Osseointegration
• Reduced bone turn over and altered bone homeostasis

103. Dental Implants and Diabetes
▪ The National Institute of Health Consensus Development Conference
Statement on Dental Implants(USA) 1998 “A well-controlled diabetic has no
contraindications provided that proper preoperative assessment is
carefully done.”
▪ No longer an absolute contraindication.
(Nevins et al.Int J Oral Maxillofac Implants. 1998)
▪ Implants can be placed in controlled diabetic patients.
▪ Hassan et al. Implant Dent 2002 showed 95.7% success rate (only 5 implants
failed in 113 implants).
▪ Kapur et al 1998 concluded that implants can be successfully used in diabetic
patients with low to moderate levels of metabolic control
▪ Shernoff et al 1994 showed 92.7% success.
103

104. 104
MANAGEMENT

105. Treatment
105

106. ▪ Interventions for Diabetes Mellitus
▪ A.Dietary Management
▪ 1. Follow individualized meal plan and snacks as scheduled
▪ Balanced diabetic diet – 50% CHO, 30% fats,, vitamins and minerals diet based on pts.
size, wt., age, occupation and activity.
▪ 2. Pt. must have adequate CHO intake to correspond to the time when insulin is most
effective
▪ 3. Routine blood glucose testing before each meal and at bedtime is necessary during
initial control, during illness and in unstable pts.
▪ 4. Do not skip meals
▪ 5. Measure foods accurately, do not estimate
106

107. ▪ 7. Advise use of complex carbohydrates to help stabilize blood
sugar. Meal should include more fiber and starch and fewer simple
or refined sugars.
▪ 8. Avoid concentrated sweets, high in sugar (jellies, jams, cakes, ice
cream)
▪ 9. If taking insulin, eat extra food before periods of vigorous
exercise
▪ 10.Avoid periods of fasting and feasting
▪ 11.Keep weight at normal level, obese diabetics should be on a
strict weight control program and should lose weight.
▪ Guidelines for the prevention, management and care of diabetes mellitus,WHO
107

108. B. Correct administration of insulin and
other hypoglycemic agents
▪ 1. Insulin in current use may be stored at room temp., all others
in ref. or cool area.
▪ 2. Avoid injecting cold insulin lead to tissue reaction.
▪ 3. Roll insulin vial to mix, do not shake, remove air bubbles from
syringe.
▪ 4. Press (do not rub) the site after injection (rubbing may alter
the rate of absorption of insulin).
▪ 5. Avoid smoking for 30 mins. after injection (cigarette smoking
absorption).
108

109.  6. Rotate sites: Failure to rotate sites may lead to
Lipodystrophy.
 Lipodystrophy – localized disturbance of fat metabolism
 Ex. Lipohypertrophy – thickening of subcutaneous tissue
at injection site, feel lumpy or hard, spongy result to
absorption of insulin making it difficult to control the pt.’s
blood glucose.
109

110. Insulin Injection Site
110

111. Insulin Effectiveness
111

112. 112

113. Factors that influence the body’s
need for insulin
▪ 1. need : trauma, infection, fever, severe
psychological or physical stress, other illnesses
▪ 2. need : active exercise
113

114. ▪ • Hypoglycemia
▪ low blood glucose (usually below 60mg/dl) results from too
much insulin, not enough food, and/or excessive physical
activity may occur 1-3 hrs after regular insulin injection
▪ • Signs and symptoms:
▪ 1. Sweating, tremor, pallor, tachycardia, palpitations and
nervousness caused by release of epinephrine from the CNS
when blood glucose falls rapidly
▪ 2. Headache, light-headedness, confusion, numbness of lips
and tongue, slurred speech, drowsiness and convulsions.
114

115. ▪ Management of Hypoglycemia
▪ 1. Give simple sugar orally if pt. is conscious and can swallow –
orange juice, candy, glucose tablets, lump of sugar.
▪ 2. Give Glucagon if pt. is unconscious or cannot take sugar by
mouth.
▪ 3. As soon as pt. regains consciousness, he should be given
carbohydrate by mouth.
▪ 4. If pt. does not respond to the above measures, he is given 50
ml of 50% glucose.
▪ I.V. or 1000 ml of 5%-10% glucose in water I.V.
115

116. ▪ Oral Antidiabetic Agents
116

117. 117

118. 118
Dental Management of Diabetic
Patients

119. Dental Management
Considerations
To minimize the risk of an intraoperative
emergency, clinician need to consider the
following before initiating dental treatment.
▪ Medical history :
▫ Glucose levels
▫ Frequency of hypoglycemic episodes
▫ Medication and dosage.
▫ Consultation
119

120. ▪ Scheduling of visits
▫ Morning appt.
▫ Do not coincide with patients peak 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
120

121. ▪ During treatment
▫ The most common complication of DM is
hypoglycemic episode.
▫ Hyperglycemia
▪ After treatment
▫ Infection control
▫ Dietary intake
▫ Medications : Salicylates increase insulin secretion
and sensitivity avoid aspirin.
121

122. ▫ 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
122

123. ▫ 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
▫ 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)
123

124. 124
Emergency Management

125. Emergencies
▪ Hypoglycemia
▪ Diabetic keto acidosis
▪ Hyperosmolar Non-Ketotic Hyperglycaemia
▪ Lactic Acidosis
125

126. Hypoglycemia
126
Early Stage Moderate Stage Severe Stage
Diminished cerebral
function
Changes in mood
Hunger
Nausea
Sweating
Tachycardia
Increased anxiety
Bizarre behavioral
patterns
Unconsciousness
Seizure activity
Hypotension
Hypothermia
Coma
Death

127. Emergency Management
▪ 15 grams of fast-acting oral carbohydrate.
▪ Measure blood sugar.
▪ Loss of consciousness, 25-30ml 50% dextrose
solution iv. over 3 min period.
▪ Glucagon 1mg i.m or s.c
127

128. Severe hyperglycemia
▫ A prolonged onset
▫ Ketoacidosis may develop with nausea,
vomiting, abdominal pain and acetone odor.
128

129. ▪ Hyperglycemia need medication intervention
and insulin administration.
▪ While emergency, give glucose first !
▪ Small amount is unlikely to cause significant
harm.
129

130. Drugs Causing Hyperglycemia
▪ Glucagon
▪ Corticosteroids
▪ Diazoxide
▪ Intravenous dextrose
▪ Diuretics
▪ Epinephrine
▪ Estrogens
▪ Isoniazid
▪ Lithium
▪ Phenothiazines
▪ Phenytoin
▪ Salicylates (acute toxicity)
▪ Triamterene
▪ Tricyclic antidepressants
▪ Atypical antipsychotics, especially olanzapine
130

131. Drugs Causing Hypoglycemia
▪ Acetaminophen
▪ Alcohol
▪ Anabolic steroids
▪ Clofibrate
▪ Disopyramide
▪ Gemfibrozil
▪ Monoamine oxidase inhibitors (MAOIs)
▪ Pentamidine
▪ Sulfonylurea medications
131

132. Newer Insulin Inhaler
▪ It is a rapid-acting, fine dry-powdered
▪ insulin that enters the bloodstream very
rapidly.
It is especially indicated for pre-meal
insulin administration.
132

133. Future Trends in Management
▪ Oral Insulins
▪ Amylin analogues ( Pramilintide)
▫ Secreted by beta cells
▫ Modulates gastric emptying
▫ Prevent post prandial rise of glucagon
▫ Produces satiety – causing weight loss
▪ Exenedin -4 (Incretin Hormone)
▫ Mimics incretin hormones of mammals
▫ Enhances insulin secretion
▫ Slows gastric emptying
▫ Reduces body weight
(Mealey et al. 2007 Perio 2000)
133

134. Conclusion
▪ Commonly encountered in dental office.
▪ Complete medical history to be known by the
dentist.
▪ Dentist should be aware of hypoglycemia and
should be in a position to manage it.
▪ Dentist plays a major role in oral hygiene
education .
▪ Patients should be made aware of the
periodontitis-diabetes inter relationship.
134

135. References:
 Texbook of medicine Davidsons’s.
 Carranza 11th edition.
 Textbook of Periodontal Medicine.
 Schmidt AM, Weidman E, Lalla E, Du Yan S, Hori O, Cao R, Brett JG, Lamster IB. Advanced
glycation endproducts (AGEs) induce oxidant stress in the gingiva: a potential mechanism
underlying accelerated periodontal disease associated with diabetes. Journal of
periodontal research. 1996 Oct 1;31(7):508-15.
 Al-Maskari AY, Al-Maskari MY, Al-Sudairy S. Oral manifestations and complications of
diabetes mellitus: a review. Sultan Qaboos University Medical Journal. 2011 May;11(2):179.
 Guidelines for the prevention, management and care of diabetes mellitus,WHO.
 Janket SJ, Wightman A, Baird AE, Van Dyke TE, Jones JA. Does periodontal treatment
improve glycemic control in diabetic patients? A meta-analysis of intervention studies.
Journal of dental research. 2005 Dec;84(12):1154-9.
 Grover HS, Luthra S. Molecular mechanisms involved in the bidirectional relationship between diabetes
mellitus and periodontal disease. Journal of Indian Society of Periodontology. 2013 May;17(3):292.
135