ORAL MANIFESTATIONS OF DIABETES MELLITUS

  • Endocrine function of pancreas is performed by the islets of Langerhans.
  • Human pancreas contains about 1 to 2 million islets.

Consist of four types of cells:

  1. A cells or α-cells, which secrete glucagon.
  2. B cells or β-cells, which secrete insulin.
  3. D cells or δ-cells, which secrete somatostatin.
  4. F cells or PP cells, which secrete pancreatic polypeptide.
  FeaturesInsulinGlucagon
  Source of secretionβ-cells of islets of langerhans.α-cells of islets of langerhans.
  Action on carbohydrate                metabolism

Decreases blood glucose level by:

1.    Facilitating transport and uptake of glucose by all cells except liver cells.

2.    Increasing peripheral utilization of glucose.

3.    Increasing glycogenesis in liver and muscle.

4.    Preventing glycogenolysis.

5.    Preventing gluconeogenesis

Increases blood glucose level by:

1.Facilitating glucose transport into liver cells.

2.Increasing glycogenolysis.

3.Increasing gluconeogenesis.

  Action on protein                          metabolism

1.    Facilitates amino acid transport.

2.    Accelerates protein synthesis.

3.    Prevents protein catabolism.

4.    Prevents conversion of proteins into glucose.

1.    Increases transport of amino acids into liver cells.

2.    Increases utilization of amino acids for gluconeogenesis.

  Action on fat                                metabolism

1.    Increases synthesis and storage of fat.

2.    No ketogenic effect.

1.    Increases lipolysis.

2.    Promotes ketogenesis.

  Blood fatty acidsDecreasesIncreases
  Hypersecretion leads toHypoglycemiaHyperglycemia
  Hyposecretion leads toDiabetes mellitusHypoglycemia

Somatostatin is secreted from:

  1. Hypothalamus
  2. D cells (δ-cells) in islets of Langerhans of pancreas.
  3. D cells in stomach and upper part of small intestine.
  1. Somatostatin acts within islets of Langerhans and inhibits β and α cells, i.e. it inhibits the secretion of both glucagon and insulin.
  2. It decreases the motility of stomach, duodenum and gallbladder.
  3. It reduces the secretion of gastrointestinal hormones gastrin, cholecystokinin, gastric inhibitory peptide and vasoactive intestinal peptide.
  4. Hypothalamic somatostatin inhibits the secretion of GH and TSH from anterior pituitary. That is why, it is also called growth hormone-inhibitory hormone (GHIH).
  • Diabetes mellitus represents a group of metabolic diseases that are characterised by hyperglycaemia due to a total or relative lack of insulin secretion and insulin resistance or both.
  • Diabetes’ means ‘polyuria’ and ‘mellitus’ means ‘honey’. The name ‘diabetes mellitus’ was coined by Thomas Willis, in 1675.

Diabetes mellitus classified in to Type I and Type II.

Type I diabetes mellitus

  • Due to deficiency of insulin (destruction of β-cells in islets of Langerhans).
  • Occur at any age, usually occurs before 40 years of age.
  • This requires insulin injection.
  • So it is also called insulin-dependent diabetes mellitus (IDDM).
  • When it develops at infancy or childhood, it is called juvenile diabetes.
  • Develops rapidly and progresses at a rapid phase.
  • Not associated with obesity, but may be associated with acidosis or ketosis.
  • Degeneration of β-cells in the islets of Langerhans of pancreas.
  • Destruction of β-cells by viral infection.
  • Congenital disorder of β-cells.
  • Destruction of β-cells during autoimmune diseases.
  1. Latent autoimmune diabetes in adults (LADA):
  • Slow onset diabetes.
  • Slow progress than IDDM and it occurs in later life after 35 years.
  • It is difficult to distinguish LADA from type II diabetes mellitus, since pancreas takes longer period to stop secreting insulin.
  1. Maturity onset diabetes in young individuals (MODY):
  • Rare inherited form occurs before 25 years.
  • Due to hereditary defects in insulin secretion.
  • Type II diabetes mellitus is due to insulin resistance (failure of insulin receptors to give response to insulin). So, the body is unable to use insulin. About 90% of patients have type II diabetes mellitus.
  • Occurs after 40 years.
  • Only some forms require insulin.
  • It can be controlled by oral hypoglycemic drugs. So it is also called non insulin dependent diabetes mellitus (NIDDM).
  • Type II diabetes mellitus may or may not be associated with ketosis.
  • Often it is associated with obesity.

In this, structure and function of β-cells and blood level of insulin are normal. But insulin receptors may be less, absent or abnormal, resulting in insulin resistance.

Common causes of insulin resistance are:

  1. Genetic disorders (significant factors causing type II diabetes mellitus)
  2. Lifestyle changes such as bad eating habits and physical inactivity leading to obesity.
  3. Stress.
  1. Gestational diabetes:
  • It occurs during pregnancy.
  • Due to many factors such as hormones secreted during pregnancy, obesity and lifestyle before and during pregnancy.
  • Usually disappears after delivery of the child but woman has high risk of development of type II diabetes
  1. Pre-diabetes:
  • Also called chemical, subclinical, latent or borderline diabetes.
  • It is the stage between normal condition and diabetes.
  • Person does not show overt (observable) symptoms of diabetes but there is an increase in blood glucose level.
  • Though it is reversible, the affected persons are at a high risk of developing type II diabetes mellitus.

  Features

Type I (IDDM)

Type I I(NIDDM)

  Age of onset

Usually before 40 year

Usually after 40 year

  Major cause

Lack of insulin

Lack of insulin receptor

  Insulin deficiency

Yes

Partial deficiency

  Immune destruction of β-cells

Yes

No

  Involvement of other endocrine disorders

No

Yes

  Hereditary cause

Yes

May or may not be

  Need for insulin

Always

Not in initial stage

May require in later stage

  Insulin resistance

No

Yes

  Control by oral hypoglycemic agents

No

Yes

  Symptoms appear

Rapidly

Slowly

  Body weight

Usually thin

Usually overweight

  Stress-induced obesity

No

Yes

  Ketosis

Yes

May or may not be

Manifestations of DM develop because of three major setbacks of insulin deficiency:

  1. Increased blood glucose level (300 to 400 mg/dL) due to reduced utilization by tissue.
  1. Mobilization of fats from adipose tissue for energy, leading to elevated fatty acid content in blood. This causes deposition of fat on the wall of arteries and development of atherosclerosis.
  1. Depletion of proteins from the tissues.

Signs and symptoms of diabetes mellitus:

  • Glucosuria
  • Osmotic diuresis
  • Polyuria
  • Polydipsia
  • Polyphagia
  • Asthenia
  • Acidosis
  • Acetone breathing
  • Kussmaul breathing (increase in rate and depth of respiration)
  • Circulatory shock
  • Coma

Glucosuria is the loss of glucose in urine. When glucose level rises above 180 mg/dL in blood, glucose appears in urine. It is the renal threshold level for glucose.

Caused by osmotic effects. Excess glucose in the renal tubules develops osmotic effect. Osmotic effect decreases the reabsorption of water from renal tubules, resulting in diuresis. It leads to polyuria and polydipsia.

Excess urine formation with increase in the frequency of voiding urine is called polyuria.

Increase in water intake is called polydipsia. Excess loss of water decreases the water content and increases the salt content in the body. This stimulates the thirst center in hypothalamus.

Polyphagia means the intake of excess food.

  • During insulin deficiency, glucose cannot be utilized by the peripheral tissues for energy. So, a large amount of fat is broken down to release energy. It causes the formation of excess ketoacids, leading to acidosis.
  • One more reason for acidosis is that the ketoacids are excreted in combination with sodium ions through urine (ketonuria).

In severe ketoacidosis, acetone is expired in the expiratory air, giving the characteristic acetone or fruity breath odor. It is a life-threatening condition of severe diabetes.

  1. ·         Gingivitis.
  2. ·         Periodontitis.
  3. ·         Dental caries.
  4. ·         Tooth loss.
  5. ·         Oral candidiasis.
  6. ·         Oral mucosal lesions such as traumatic ulcers and irritation.
  7. ·         Fibroma.
  8. ·         Impaired wound healing.
  9. ·         Xerostomia.
  10. ·         Salivary gland hypofunction.
  11. ·         Sialosis.
  12. ·         Burning mouth sensation.
  13. ·         Impairment of taste.

Following mechanism is involved:

  • The polyol path­way converts glucose into the enzyme sorbitol by aldose reductase that causes tissue damage and numerous other diabetic complications.
  • Formation of advanced glycosylation end products (AGE), due to binding of glucose to proteins, lipids and nucleic acids, results in the alteration of structures and functions, in addition to its deposition in specific or­gans causes various complications.
  • Atheroma deposits are formed and accumulate in the basal membrane and lumen causing decreased cellular defense capacity and impaired polymorphonuclear leu­kocyte response.

Advanced periodontal disease occurs due to number of structural and functional hyperglycaemia-related alterations:

  • Thickening of basement membranes of blood vessels (microangiopathy) which leads to deterioration of microcirculation in periodontal tissue and decreased supply of oxygen and nutrients to tissues and accumulation of harmful metabolites.
  • Impaired functions of polymorphonuclear leukocytes leading to abnormalities of adherence, phagocytosis and chemotaxis.
  • Impaired gingival fibroblast proliferation and collagen synthesis.
  • Enhanced collagenase activity.
  • Formation of AGEs that bind to monocyte receptors and induce production of inflammatory mediators like TNF, prostaglandin E-2 and interleukin-1.

All these mechanisms may lead to impaired host resistance and accelerated inflammatory host response and result in loss of periodontal fibres, loss of the alveolar supporting bone, and eventually loss of teeth.

Poor metabolic control, salivary gland hypofunction, and high salivary glucose concentrations promotes growth of Streptococcus mutans and Lactobacillus. So diabetic patients are more at high risk for dental caries.

Impaired wound healing in diabetes is due to:

  • Reduced host response to inflammation due to impairment of polymorphonuclear leukocyte functions leading to abnormalities of adherence, phagocytosis, chemotaxis, and intracellular killing.
  • Synthesis of collagen in extracellular matrix gets decreased, the degradation of newly synthesised collagen is accelerated and collagenase activity is increased.
  • Formation of AGEs may lead to increased thickness of basement membranes of blood vessels, which impairs the supply of oxygen and nutrients to tissues.
  • Dehydration, as the result of prolonged hyperglycaemia and consequently polyuria, is major cause of xerostomia and salivary gland hypofunction in diabetics.
  • Gradual degeneration of salivary gland tissue can lead to salivary hypofunction and altered salivary composition.
  • 10-25% of type 1 or type 2 diabetics may develop a bilateral asymptomatic enlargement of the parotid glands and, more rarely, of the submandibular glands, known as diabetic sialosis.
  • Enlarged parotid and submandibular glands are characterized by fatty infiltration, fibrous tissue, enlargement of acinar cell and reduction in acinar tissue, but without signs of inflammation.

Candidal colonization increases in diabetic patient due to:

  • Poor metabolic control.
  • High concentrations of glucose in the blood and saliva.
  • Reduced salivary flow rates, low salivary pH.
  • Reduction in antimicrobial substances in the saliva.

Oral infection with Candida may clinically present as median rhomboid glossitis, atrophic glossitis, denture stomatitis, pseudomembranous candidiasis and angular cheilitis.

Diabetic neuropathy (DN) is a common disorder and is defined as signs and symptoms of peripheral nerve dysfunction in a patient with diabetes mellitus (DM) in whom other causes of peripheral nerve dysfunction have been excluded.

Symmetric

  • Diabetic polyneuropathy.
  • Painful autonomic neuropathy.
  • Painful distal neuropathy with weight loss ‘‘diabetic cachexia’’.
  • Insulin neuritis.
  • Polyneuropathy after ketoacidosis.
  • Polyneuropathy with glucose impairment.
  • Chronic inflammatory demyelinating polyneuropathy with diabetes mellitus.

 Asymmetric

  • Radiculoplexoneuropathies
    1. Lumbosacral
    2. Thoracic
    3. Cervical
  • Mononeuropathies
  • Median neuropathy at wrist
  • Ulnar neuropathy at the elbow
  • Peroneal neuropathy at the fibular head
  • Cranial neuropathy

Hyperglycaemia induces:

  • Rheological changes, which increases endothelial vascular resistance and reduces nerve blood flow.
  • Depletion of nerve myoinositol through a competitive uptake mechanism.
  • Activation of polyol pathway in the nerve through enzyme aldose reductase leads to accumulation of sorbitol and fructose in the nerve and induces nonenzymatic glycosylation of structural nerve proteins.
  • Oxidative stress.
  • Activation of protein kinase C, also linked to vascular damage in DN.

These changes result in abnormal neuronal, axonal, and Schwann cell metabolism, which results in impaired axonal transport.

In diabetic patients endoneural hypoxia is produced by increased vascular resistance and reduced blood flow in the nerve. Hypoxia leads to further capillary damage, which in turn aggravates disturbance in axonal transport and reduced Na-K ATPase activity leading to axonal atrophy and impairment of nerve conduction.

Glucose Tolerance Test

  • Patient scheduled for oral GTT is instructed to eat a high carbohydrate diet for at least 3 days prior to the test and come after an overnight fast on the day of the test (for at least 8 hours).
  • A fasting blood sugar sample is first drawn.
  • Then 75 gm of glucose dissolved in 300 ml of water is given.
  • Blood and urine specimen are collected at half-hourly intervals for at least 2 hours(four samples).
  • Blood or plasma glucose content is measured and urine is tested for glucosuria to determine the approximate renal threshold for glucose.

Revised criteria for diagnosis of diabetes by oral GTT (as per American Diabetes Association, 2007).

Fasting (for > 8 hours) value

  • Below 100 mg/dl (< 5.6 mmol/L): Normal fasting value
  • 100-125 mg/dl (5.6-6.9 mmol/L): Impaired fasting glucose (IFG)
  • 126 mg/dl (7.0 mmol/L) or more: Diabetes mellitus

Two-hour after 75 gm oral glucose load

  • < 140 mg/dl (< 7.8 mmol/L): Normal post-prandial GTT
  • 140-199 mg/dl (7.8-11.1 mmol/L): Impaired post-prandial glucose tolerance (IGT)
  • 200 mg/dl (11.1 mmol/L) or more: Diabetes mellitus

Random value

  • 200 mg/dl (11.1mmol/L) or more in a symptomatic patient: Diabetes mellitus

Glycosylated haemoglobin test

  • It determines the blood glucose status over the 30 to 90 days prior to collection of the blood sample.
  • In circulation glucose attaches to a portion of the hemoglobin on red blood cells.
  • The higher the plasma glucose levels over time, the greater is the percentage
  • of hemoglobin that becomes glycated.

There are two different glycated hemoglobin assays:

  • Hemoglobin A1 (HbA1):<8%(>10%- poorer glycemic control)
  • Hemoglobin A1c (HbA1c): 6.0-6.5%.

Fructosamine test

  • Determines the blood glucose status over 2-4 weeks prior to test
  • Helps in managing women with gestational diabetes.
  • The normal range for fructosamine is 2.0 to 2.8 mmol/L.

Self–blood glucose monitoring (SBGM)

  • Small handheld glucometers are used.
  • Glucometers use a small drop of capillary blood from a fingerstick sample to assess glucose levels within seconds.

Other tests:

Extended GTT:

  • The oral GTT is extended to 3-4 hours for appearance of symptoms of hyperglycaemia.
  • Useful test in cases of reactive hypoglycaemia of early diabetes.

Intravenous GTT

  • Performed in persons who have intestinal malabsorption or in postgastrectomy cases.

Cortisone-primed GTT

  • Useful investigative aid in cases of potential diabetics.

Insulin assay

  • Plasma insulin can be measured by radioimmunoassay and ELISA technique.

Benedict’s qualitative test

  • Detects any reducing substance in the urine and is not specific for glucose.
  • More sensitive and glucose specific test is dipstick method based on enzyme-coated paper strip which turns purple when dipped in urine containing glucose.

  Test

Result

Prediabetes category

  FPG (mmol/L)

6.1 to 6.9

IFG

  2hPG in a 75 g OGTT (mmol/L)

7.8 to11.0

IGT

  A1C (%)

6.0 to 6.4

Prediabetes

(2hPG, 2-hour plasma glucose; A1C, glycated hemoglobin; FPG, fasting plasma

glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; OGTT, oral glucose tolerance test.)

  1. Medical history
    • To assess the glycemic control.
    • Recent blood glucose levels.
    • Frequency of hypoglycemic episodes.
    • Antidiabetic drugs being used:
    1. Dosage.
    2. Time of administration.
    3. Frequency.
    • Drugs which alter the glucose levels through interference with insulin or carbohydrate metanolism.
    • Drugs with hyperglycemic effects:
    1. Corticosteroids.
    2. Thiazides
    3. Phenytoin
    4. Epinephrine
    5. Oral contraceptives
    6. Thyroid products
    7. Calcium channel blockers.
    • Drugs which potentiate the hypoglycemic effects of sulfonylureas:
    1. Salicylates
    2. Sulfonamides
    3. ACEinhibitors
    4. MAO inhibitors
    5. Beta adrenergic blockers.
  2. Scheduling the visit
    • Morning appointments are advisable because endogenous cortisol levels are higher at that time.
    • For patient taking insulin, appointment should be scheduled so that they does not coincide with the peaks of insulin activity.
  3. Diet
    • Make sure that patient has eaten normally and taken medications as usual.
    • If the patient skips breakfast but takes normal dose of insulin, risk of hypoglycemic shock is there.
  4. Before starting treatment
    • Blood glucose levels should be measured.
    • If sugar level <70mg/dl, oral glucose to be given before treatment to decrease the risk of hypoglycemic shock.
  5. During treatment
    • Most common complication in dental office is hypoglycemic shock.
    • When insulin or other antidiabetic drugs exceed physiological needs there may be severe decline in blood sugar levels.
    • Maximum risk is during peak insulin activities.
  6. After treatment
    • Patients with poorly controlled DM are at greater risk of developing infections and delayed wound healing.
    • Acute infections adversely affect the insulin resistance and glycemic control which inturn may further affect the body’s capacity to heal.
    • Therefore antibiotic coverage is must.
    • If the dentist anticipates that normal dietary intakes will be effected after treatment, insulin or oral antidiabetic drugs and their doses may need to be adjusted in consultation with the patient’s physician.
    • Salicylates potentiate the hypoglycemic effect of sulfonylureas and produces hypoglycemia. Therefore, aspirin and aspirin containing compounds should not be given to diabetic patients.
    • Patients with severe periodontitis, adjunctive use of tetracycline antibiotics in conjunction with mechanical periodontal therapy may have beneficial effects on glycemic control as well as on periodontal status.
  • Major issue that confronts dental practitioners when treating diabetic patients, particularly if patients are fasting.
  • Hypoglycemia usually appears in response to the stress experienced before, during or after the treatment, and cause a significant increase in perioperative morbidity and mortality.
  • More frequent in people with diabetes who take insulin.
  • Can occur in either type 1 or type 2 diabetes
  • Caused by certain oral medications, missed meals, and exercise without proper precautions.
  • The typical threshold for hypoglycemia is 70 mg/dl (3.9 mmol/l)
  • Confusion.
  • Sweating.
  • Tremors.
  • Agitation.
  • Anxiety.
  • Dizziness.
  • Tingling or numbness.
  • Tachycardia.

Severe hypoglycemia:

  • Seizures
  • Loss of consciousness

Management of hypoglycemia is as follows:

  Conscious patient

Unconscious patient

  • Administer 15 mg of simple carbohydrates
  • Repeat finger- stick glucose test in 15 minutes:

  A.   Blood glucose level > 60 mg/dl: patient should be asked to     eat or drink (for example, a sugar-sweetened beverage)

  B.   Blood glucose level < 60 mg/dl: repeat treatment of 15 g of   simple carbohydrates and check blood glucose in 15 minutes.   Continue until achieving a blood glucose level > 60mg/ dl

  • Ask the patient to notify his/ her physician

With intravenous access:

  • Administer 5 to 25 g of 50% dextrose immediately.
  • Notify the patient’s physician.

Without intravenous access:

  • Apply glucose gel inside the mouth in a semiobtund patient or treat with 1 mg of glucagon intramuscularly or subcutaneously.
  • Repeat the blood glucose test in 15 minutes.
  • Establish intravenous access and notify the patient’s physician

 

Extremely high blood glucose levels can lead to:

  • Diabetic ketoacidosis (DKA).
  • Hyperglycemic hyperosmolar nonketotic syndrome (HHNS; also k/a hyperglycemic hyperosmolar nonketotic coma).
  • Both syndromes can occur in either type 1 or type 2 diabetes, DKA is more common in type 1 and HHNS is more common in type 2.
  • Diabetic ketoacidosis and hyperosmolar nonketotic syndrome require immediate medical evaluation and treatment.
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