Diabetes, pathophysiology, investigations, oral complications, management

1. DIABETES
IN ADULTS AND IN CHILDREN
27/1/16
WEDNESDAY
PRESENTED BY –DR MONALI PRAJAPATI
MDS
ORAL MEDICINE AND RADIOLOGY

2. PHYSIOLOGY
In humans, blood glucose is tightly regulated by
homeostatic mechanisms and maintained
within a narrow range.

3. Insulin lowers blood
glucose
Supress hepatic
glucose production
Stimulate glucose uptake
in skeletal muscles, and
fat mediated by GLUT 4
glucose transported

4. Physiology

5. Metabolic effects of Insulin
INCREASE (ANABOLIC EFFECTS) DECREASE (CATABOLIC EFFECTS)
CARBOHYDRATE METABOLISM
Glucose transport (muscle, adipose tissue) Gluconeogenesis
Glucose phosphorylation Glycogenolysis
Glycogenesis
Glycolysis
Pyruvate dehydrogenase activity
Pentose phosphate shunt
LIPID METABOLISM
Triglyceride synthesis Lipolysis
Fatty acid synthesis (liver) Lipoprotein lipase (muscle)
Lipoprotein lipase activity (adipose tissue) Ketogenesis
Fatty acid oxidation (liver)
PROTEIN METABOLISM
Amino acid transport Protein degradation
Protein synthesis

6. DIABETES MELLITUS
DIABETES MELLITUS IS AN ENDOCRINAL
DISORDER CHARACTERIZED BY METABOLIC
ABNORMALITIES LIKE, HYPERGLYCEMIA,
GLUCOSURIA, HYPERLIPIDEMIA, NEGATIVE
NITROGEN BALANCE, AND SOMETIMES
KETONEMIA DUE TO ABSOLUTE OR RELATIVE
DEFICIENCY OF INSULIN.

7. AETIOLOGICAL CLASSIFICATION OF
DIABETES MELLITUS
• Type 1 diabetes [Insulin dependent or juvenile-onset
diabetes (IDDM)]
 Immune-mediated
 Idiopathic
• Type 2 diabetes [non- insulin dependent or adult onset
diabetes (NIDDM)]
• Gestational diabetes
• Other specific types

8. Other specific types
• Genetic defects of β-cell function
• Genetic defects of insulin action
• Pancreatic disease (e.g. pancreatitis, pancreatectomy, neoplastic
disease, cystic fibrosis, haemochromatosis, fibrocalculous
pancreatopathy)
• Excess endogenous production of hormonal antagonists to
insulin (e.g. growth hormone-acromegaly; glucocorticoids-
Cushing's syndrome; glucagon-glucagonoma; catecholamines-
phaeochromocytoma; thyroid hormones-thyrotoxicosis)

9. • Drug-induced (e.g. corticosteroids, thiazide diuretics, phenytoin)
• Viral infections (e.g. congenital rubella, mumps, Coxsackie virus
B)
• Uncommon forms of immune-mediated diabetes associated with
genetic syndromes (e.g. Down's syndrome; Klinefelter's
syndrome; Turner's syndrome; DIDMOAD (Wolfram's
syndrome)-diabetes insipidus, diabetes mellitus, optic atrophy,
nerve deafness; Friedreich's ataxia; myotonic dystrophy

10. TYPE I DIABETES
• Type 1 diabetes is a slowly progressive T cell-mediated
autoimmune disease in which destruction of pancreatic
β cells occur.
• Etiology:
• Hygiene hypothesis
• Viral infection (mumps, coxsackie virus B4, retrovirus, rubella,
cytomegalovirus, Epstein Barr virus)
• Bovine serum albumin in cow milk
• Stress causing release of counter regulating hormones

11. Metabolic disturbances in Type 1 diabetes

12. Type II diabetes
RESISTANCE TO THE ACTIONS OF INSULIN
IN LIVER AND MUSCLES
IMPAIRED PANCREATIC Β CELL FUNCTION

13. ETIOLOGY
 GENETIC PREDISPOSITION
 ENVIRONMENTAL FACTORS
 OVEREATING
 OBESITY
 UNDERACTIVITY
 HIGH FAT DIET (EXACERBATE INSULIN
RESISTANCE)

16. Type 1 Type 2
Typical age at onset < 40 years > 50 years
Duration of symptoms Weeks Months to years
Body weight Normal or low Obese
Ketonuria Yes No
Rapid death without
treatment with insulin
Yes No
Autoantibodies Yes No
Diabetic complications at
diagnosis
No 25%
Family history of diabetes Uncommon Common
Other autoimmune disease Common Uncommon
COMPARISION OF TYPE I AND II DIABETES

17. COMPLICATIONS OF DIABETES
 Retinopathy
 Vision changes
 Blindness
 Nephropathy (renal failure)

18.  Neuropathy
 Sensory
 Loss of sensation in hands and feet (other areas may be affected as well)
 Impotence
 Other sensory dysfunction
 Autonomic
 Gastroparesis (affects stomach emptying and other gastrointestinal
functions)
 Changes in cardiac rate, rhythm, conduction
 Other autonomic dysfunction

19.  Macrovascular disease (accelerated atherosclerosis)
 Peripheral vascular disease
 Cardiovascular (coronary artery disease)
 Cerebrovascular (stroke)
 Alterations in wound healing

20. INVESTIGATIONS
URINE TESTING:
Glucose
Ketones
Protein

21.  BLOOD TESTING:
Glucose
Glycated haemoglobin
Blood lipids

25. ESTABLISHING THE DIAGNOSIS
 PATIENT COMPLAINS OF SYMPTOMS
SUGGESTING DIABETES
 URINANALYSIS FOR GLUCOSE
 RANDOM BLOOD GLUCOSE: GREATER THAN
200mg/dl
 FASTING BLOOD SUGAR: GREATER THAN
126mg/dl
 GLUCOSE TOLERANCE TEST: Two-hour
postprandial glucose ≥ 200 mg/dL using a glucose load
containing the equivalent of 75 g of anhydrous glucose
dissolved in water

26. ORAL COMPLICATIONS
 The hard tissue manifestations
include:
Variations in tooth development
Prevalence of dental caries,
Periodontal manifestations.

27.  The soft tissue attributes include:
 Oral changes resulting from salivary gland
abnormalities.
 Taste disorders
 An increased prevalence oral mucosal lesions,
 Infections,
 Burning mouth syndrome,

28. TOOTH DEVELOPMENT
 An accelerated tooth development in diabetic children up
to age 10.5 years has been reported.
 Following this initial acceleration, steady retardation of
dental development with advancing age is eminent.
 Such a dual influence on tooth development has been
credited to stimulation of the pituitary gland in the initial
stage of diabetes that gradually becomes ‘exhausted’ over
time in type-1 diabetics

29. DENTAL CARIES
 PREDISPOSINMG FACTORS TO CARIES IN
DIABETEIC PATIENTS:
 Increased glucose levels in saliva and gingival crevicular
fluids,
 Altered plaque microflora (greater number of streptococcus
mutans and lactobacilli ),
 Reduced salivary flow.

30. PERIODONTAL DISEASES
 Distinct gingival hyperplasia
may represent the first sign of
disease onset.
 Enlarged velvety-red gingivae
that bleed readily, a typical
bluish-purple hue of the
gingivae, proliferation of
tissue at the gingival margin,
 Putrescent exudates from
periodontal pockets,
 Multiple lateral periodontal
abscesses as well as advanced
loss of supporting alveolar
bone leading to mobility of
teeth

31. Factors responsible for increased susceptibility
to periodontal disease:
 CHANGE IN FUNCTION OF HOST RESPONSE:
 Compromised polymorphonuclear leukocyte function
(resulting from impaired neutrophil adherence,
chemotaxis and phagocytosis prevent destruction of
bacteria in the periodontal pocket and markedly
enhance periodontal destruction)
 Monocytes and macrophages in diabetic individuals are
often hyper-responsive to bacterial antigens resulting in
increased production of pro-inflammatory cytokines
and mediators

32. • HYPERGLYCEMIA:
• Results in increased gingival crevicular fluid glucose level,
which alter periodontal wound healing by changing the
interaction between cells and their extracellular matrix
within the periodontium
• VASCULAR CHANGES:
• The formation of advanced glycation end products (AGE) in
the periodontal capillary basement membranes causing
membrane thickening.
• AGE- stimulated smooth muscle proliferation increases the
thickness of vessel walls

33. • These changes decrease tissue perfusion and
oxygenation.
• AGE- modified collagen in gingival blood vessel
walls binds circulating LDL, which is frequently
elevated in diabetes resulting in atheroma formation
and further narrowing of the vessel lumen
• These changes alter tissue response to periodontal
pathogens, increased tissue destruction and
diminished repair potential.

34. • CHANGES IN THE COLLAGEN METABOLISM
• Increased production of matrix metalloproteinases
collagenase which degrades newly formed collagen
• AGE modification of existing collagen decreases its
solubility
• As a result there is rapid desolution of recently
synthesized collagen by host collagenase and
preponderance of older AGE modified collagen

35. SALIVARY DYSFUNCTIONS
 Asymptomatic bilateral parotid gland enlargement in diabetics had
been reported in the early 1900’s.
 Seifert termed such non-neoplastic and non-inflammatory type of
glandular enlargement as ‘SIALADENOSIS’.
 A compensatory hyperplasia resulting from reduced insulin level and
xerostomia has been hypothesized as a probable cause.
 A hyperglycemic state leads to inhibition of UDPG-pyrophosphorylase
enzyme that produces components of salivary mucoproteins.
 Accumulation of the substrate of this enzyme has also been linked to
parotid acinar hypertrophy

36. XEROSTOMIA
 This phenomenon appears to be related to parotid
gland basement membrane variations.
 Polyuria, polydypsia and the resulting dehydration may
significantly contribute to oral dryness.

37.  Further, consumption of drugs used in the
management of diabetes and its complications may
also induce oral dryness.
 Salivary gland hypofunction in older adults has also
been attributed to undesirable hormonal,
microvascular, and neuronal changes in poorly-
controlled diabetes.

38. TASTE DYSFUNCTIONS
 Taste dysfunction has been reported to occur more
frequently in patients with poorly controlled diabetes
compared to healthy controls.
 This has been attributed to:
 Sensory dysfunction,
 Xerostomia and
 Disordered glucose receptors

39. BURNING MOUTH SYNDROME
 Burning mouth syndrome refers to a dysesthesia
characteristically described by the patient as a burning
sensation of the oral mucosa in the absence of clinically
apparent mucosal alterations.

40.  Diabetic neuropathy could be the underlying
cause of BMS in patients with diabetes.
 The nerve damage in diabetic neuropathy has
been reported to show an increase in the
Langerhans cells that are associated with
immune disturbance

41. ORAL INFECTIONS
 CANDIDIASIS
 Oral colonization with candida species is often documented as being
higher in the diabetic patient when compared to their healthy
counterparts.
 An enhanced adhesion of candida to oral epithelium is eminent in
patients with diabetes
 Oral manifestations of candidiasis such as median rhomboid glossitis
(central papillary atrophy), angular cheilitis, diffuse atrophy of tongue
papillae, as well as denture stomatitis occur more frequently in type-1
diabetics and may result in a severe burning sensation of the mouth. .

42. Factors that favor increased candidal
pseudohyphae carriage
 Neutrophil dysfunction,
 Altered host resistance due to:
 Smoking,
 Denture-wear,
 Hyperglycemia,
 Increased salivary glucose levels,
 Impaired antifungal immunoglobulins in the saliva,
 Salivary hypofunction and
 Use of immunosuppressant medications

43. MUCORMYCOSIS
 Mucormycosis (phycomycosis), a potentially fatal infection caused by
saprophytic fungus occurs in individuals with poorly controlled
diabetes.
 The most frequent oral sign of mucormycosis is ulceration of the palate
caused by necrosis resulting from invasion of a palatal vessel.
 The lesion is typically large and deep causing exposure of the
underlying bone.
 The affected individuals present with lethargy, fever, headache, nasal
discharge, facial cellulitis and anesthesia

44. BACTERIAL INFECTIONS
 An increased risk of infection is eminent in the hyperglycemic patient
owing to:
 Compromised neutrophil adherence, chemotaxis, phagocytosis,
 Bactericidal activity and
 Poor cell-mediated immunity.
 This results in an increased incidence of dry sockets (alveolar osteitis) and
osteomyelitis, frequently after mandibular extractions due to a decreased
vascular supply to the mandible as a consequence of atherosclerosis in the
diabetic.

45.  Ueta E et al found statistically significant elevation of C-
reactive protein levels in odontogenic bacterial infections in
the diabetics.
 Suppression of neutrophil superoxide production by C-
reactive protein derived degradation products may be
ascribed to an increased severity of inflammatory changes
and odontogenic infections in the diabetic patients.

46. DELAYED WOUND HEALING
 POSSIBLE CAUSES:
 COMPROMISED NEUTROPHIL FUNCTION
 REDUCED BLOOD FLOW
 DECLINE IN INNATE IMMUNITY
 DECREASED GROWTH FACTOR
PRODUCTION

47. LICHEN PLANUS AND LICHENOID
RACTIONS
 Diabetes mellitus has been linked to oral lichen planus
and hypertension, a triad referred to as the Grinspan’s
syndrome.
 Presently the reported associations between oral lichen
planus and systemic diseases remain controversial.
 A 10% - 85% prevalence of diabetes mellitus in
patients with oral lichen planus has been documented
in the past.
 According to a recent study however, no association
between oral precancerous lesions such as lichen planus
and diabetes mellitus has been found.

48.  Lichenoid reactions may be encountered in diabetics
resulting from the use of:
 Non- steroidal anti-inflammatory drugs,
 Angiotensin-converting enzyme inhibitors, chlorpropamide and
 Other oral hypoglycemic or
 Antihypertensive medications,

49. DENTAL MANAGEMENT CONSIDERATIONS
 MEDICAL HISTORY
 Assess glycemic control
 Enquire about medications
 As hypoglycemic action of sulphanylureas may be potentiated by protein
bound drugs like salicylates, β adrenergic blockers, sulfonamides,
angiotensin converting enzymes etc,
 Epinephrine, corticosteroids, thiazides, phenytoin, calcium channel
blockers are hyperglycemic,
 Patients requiring major surgical procedures may require dose
alterations
 Any complications of diabetes mellitus (cardiovascular or renal disease),
will have their own effects on dental treatment

50.  APPOINTMENT TIME:
 Decided based on individuals medical regimen
 Conventional wisdom holds that diabetic patients
should receive treatment in the morning
 Best to plan treatment before or after peaks of
insulin activity to reduce risk of hypoglycemic
reactions

51.  DIET
 Dental treatment results in post-operative
discomfort hence diet changes are required
 Procedures like conscious sedation where patients
require to be nil by mouth, diet alteration is
required.

52.  STRESS REDUCTION
 Endogenous production of epinephrine & cortisol
increase during stressful situations.
 These hormones elevate blood glucose levels and
interfere with glycemic control
 Adequate pain control and stress reduction are
therfore important

53. DIABETIC EMERGENCY IN DENTAL OFFICE
 HYPOGLYCEMIA
 Signs and symptoms include:
 confusion, sweating, tremors, agitation, anxiety,
dizziness, tingling or numbness, and tachycardia.
 Severe hypoglycemia may result in seizures or loss of
consciousness.

54. CAUSES
 Missed, delayed or inadequate meal
 Unexpected or unusual exercise
 Alcohol
 Errors in oral hypoglycaemic agent or insulin dose/schedule/ administration
 Poorly designed insulin regimen, particularly if predisposing to nocturnal hyperinsulinaemia
 Lipohypertrophy at injection sites causing variable insulin absorption
 Gastroparesis due to autonomic neuropathy
 Malabsorption, e.g. coeliac disease
 Unrecognised other endocrine disorder, e.g. Addison's disease
 Factitious (deliberately induced)
 Breastfeeding by diabetic mother

55. TREATMENT
 If patient is awake and able to take food by mouth, give 15
g oral carbohydrate in one of the following forms:
 4–6 oz fruit juice or soda
 3–4 tsp table sugar
 hard candy
 cake frosting
 If patient is unable to take food by mouth and IV line is in
place, give
 25–30 mL D50 or 1 mg glucagon.
 If patient is unable to take food by mouth and IV line is not
in place, give 1 mg glucagon subcutaneously or
intramuscularly.

56. DENTAL MANAGEMENT OF DIABETES
TYPE I DIABETIC PATIENTS
NON-INVASIVE
PROCEDURES
• Well controlled patients can be treated as non-diabetic.
• In poorly controlled diabetes, treatment should be delayed till
good metabolic control is achieved.
INVASIVE
DENTAL
PROCEDURE
• Blood glucose should be measured pre-operatively.
• If it is between 100-200mg/dl, procedure can be performed.
• In well controlled diabetics, prior to intervention half the daily
dose of insulin must be taken and whole dose with supplement of
rapid acting insulin after procedure.
• If more than 2oomg/dl then, an intravenous infusion of 10%
dextrose is initiated & rapid acting insulin administered
subcutaneously.
• If treatment lasts more than 1hour, hourly glucose level must be
measured.

57. TYPE II DIABETIC PATIENTS
NON-INVASIVE
PROCEDURES
• Well controlled patients can be treated as non-
diabetic.
• In poorly controlled diabetes, treatment should be
delayed till good metabolic control is achieved.
INVASIVE DENTAL
PROCEDURE
• Blood glucose should be measured pre-
operatively.
• Patients being treated with oral hypoglycemic
agents should take their normal dose in morning
and eat their regular diet.

58. REFERENCES
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