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:
- A cells or α-cells, which secrete glucagon.
- B cells or β-cells, which secrete insulin.
- D cells or δ-cells, which secrete somatostatin.
- F cells or PP cells, which secrete pancreatic polypeptide.
|Source of secretion||β-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.
|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 acids||Decreases||Increases|
|Hypersecretion leads to||Hypoglycemia||Hyperglycemia|
|Hyposecretion leads to||Diabetes mellitus||Hypoglycemia|
Somatostatin is secreted from:
- D cells (δ-cells) in islets of Langerhans of pancreas.
- D cells in stomach and upper part of small intestine.
- Somatostatin acts within islets of Langerhans and inhibits β and α cells, i.e. it inhibits the secretion of both glucagon and insulin.
- It decreases the motility of stomach, duodenum and gallbladder.
- It reduces the secretion of gastrointestinal hormones gastrin, cholecystokinin, gastric inhibitory peptide and vasoactive intestinal peptide.
- 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.
- 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.
- 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:
- Genetic disorders (significant factors causing type II diabetes mellitus)
- Lifestyle changes such as bad eating habits and physical inactivity leading to obesity.
- 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
- 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.
Type I (IDDM)
Type I I(NIDDM)
Age of onset
Usually before 40 year
Usually after 40 year
Lack of insulin
Lack of insulin receptor
Immune destruction of β-cells
Involvement of other endocrine disorders
May or may not be
Need for insulin
Not in initial stage
May require in later stage
Control by oral hypoglycemic agents
May or may not be
Manifestations of DM develop because of three major setbacks of insulin deficiency:
- Increased blood glucose level (300 to 400 mg/dL) due to reduced utilization by tissue.
- 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.
- Depletion of proteins from the tissues.
Signs and symptoms of diabetes mellitus:
- Osmotic diuresis
- Acetone breathing
- Kussmaul breathing (increase in rate and depth of respiration)
- Circulatory shock
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.
- · Gingivitis.
- · Periodontitis.
- · Dental caries.
- · Tooth loss.
- · Oral candidiasis.
- · Oral mucosal lesions such as traumatic ulcers and irritation.
- · Fibroma.
- · Impaired wound healing.
- · Xerostomia.
- · Salivary gland hypofunction.
- · Sialosis.
- · Burning mouth sensation.
- · 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.
- 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.
- Median neuropathy at wrist
- Ulnar neuropathy at the elbow
- Peroneal neuropathy at the fibular head
- Cranial neuropathy
- 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
- 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%.
- 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.
- 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.
- Performed in persons who have intestinal malabsorption or in postgastrectomy cases.
- Useful investigative aid in cases of potential diabetics.
- 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.
6.1 to 6.9
2hPG in a 75 g OGTT (mmol/L)
6.0 to 6.4
(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.)
- Medical history
- To assess the glycemic control.
- Recent blood glucose levels.
- Frequency of hypoglycemic episodes.
- Antidiabetic drugs being used:
- Time of administration.
- Drugs which alter the glucose levels through interference with insulin or carbohydrate metanolism.
- Drugs with hyperglycemic effects:
- Oral contraceptives
- Thyroid products
- Calcium channel blockers.
- Drugs which potentiate the hypoglycemic effects of sulfonylureas:
- MAO inhibitors
- Beta adrenergic blockers.
- 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.
- 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.
- 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.
- 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.
- 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)
- Tingling or numbness.
- Loss of consciousness
Management of hypoglycemia is as follows:
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
With intravenous access:
Without intravenous access:
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.
- Sembulingam K, Sembulingam P Essentials of Medical Physiology 6th edition
- Jaypee brothers medical publishers (p) ltd;Endocrine Functions of Pancreas page 415-24
- Mealey BL. Diabetes and periodontal disease: two sides of a coin. Compend Contin Educ Dent. 2000;21:943–6, 948-956.
- Bender IB, Bender AB. Diabetes mellitus and the dental pulp. J Endod. 2003;29:383-9.
- Leeper SH, Kalkwarf KL, Strom EA. Oral status of ‘‘controlled’’ adolescent Type 1 diabetics. J Oral Med 1985;40:127-133.
- Oliver RC, Tervonen T. Diabetes – A risk factor for periodontitis in adults? J Periodontol 1994;65:530-538.
- Twetman S, Nederfors T, Stahl B, Aronson S. Two-year longitudinal observations of salivary status and dental caries in children with insulin-dependent diabetes mellitus. Pediatr Dent 1992; 14:184-188.
- Twetman S, Johansson I, Birkhed D, Nederfors T. Caries incidence in young type 1 diabetes mellitus patients in relation to metabolic control and caries-associated risk factors. Caries Res 2002; 36:31-35.
- Swanljung O, Meurman JH, Torkko H, Sandholm L, Kaprio E, Maenpaa J. Caries and saliva in 12-18-year-old diabetics and controls. Scand J Dent Res 1992;100:310-313.
- Sreebny LM, Yu A, Green A, Valdini A. Xerostomia in diabetes mellitus. Diabetes Care 1992;15:900-904.
- Russotto SB. Asymptomatic parotid gland enlargement in diabetes mellitus. Oral Surg 1981;52:594-598.
- Donath K, Seifert G. Ultrastructural studies of the parotid glands in sialadenosis. Virchows Arch A Pathol Anat Histol 1975;365: 119-135.
- Lindeberg A, Andersen L. Size and composition of the submandibular glands in late onset diabetes. Arch Otorhinolaryngol 1987;244:100-103.
- Guggenheimer J, Moore PA, Rossie K, Myers D, Mongelluzzo MB, Block HM, et al. Insulin-dependent diabetes mellitus and oral soft tissue pathologies. I. Prevalence and characteristics of noncandidal lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000a;89:563-569.
- Vitkov L, Weitgasser R, Lugstein A, Noack MJ, Fuchs K, Krautgartner WD. Glycaemic disorders in denture stomatitis. J Oral Pathol Med 1999;28:406-409.
- Bansal V, J Kalita J, Misra UK Diabetic neuropathy Postgrad Med J 2006;82:95–100
- Álamo MS, Soriano YJ, Pérez MGS Dental considerations for the patient
with diabetes. J Clin Exp Dent. 2011;3(1):e25-30.
18. Mealey BL Dental management of the diabetic patient. Available from: http://www.health.am/db/diabetic-patient-dental-management/
- Mealey BL Diabetic emergencies in the dental office available from: http://www.health.am/db/diabetic-emergencies/.