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1. MANAGEMENT OF
PATIENTS WITH
DIABETES MELLITUS
PRESENTED BY
CHANDINI RAVIKUMAR (1ST YEAR PG)

2. INTRODUCTION
 Diabetes mellitus (DM)- characterized by an increase in plasma blood glucose levels (>140 mg/dl)
 Most commonly due to type 1 or type 2 diabetes.
 Type 1 DM
 Insulin-dependent DM (IDDM)
 Juvenile onset
 Autoimmune destruction of insulin-producing beta cells
 Absolute insulin deficiency
 Requires insulin replacement therapy.
 Type 2 DM
 Non-insulin dependent DM (NIDDM)
 Maturity onset
 Resistance to the action of insulin, and inability to produce sufficient insulin to overcome ‘insulin resistance’.
 Initially can be treated without insulin replacement therapy.

5. GLUCOSE ABSORPTION AND HOMEOSTASIS

6. METABOLIC ACTIONS OF INSULIN

7. AETIOLOGICAL CLASSIFICATION OF DM
 Type 1 diabetes
 Immune-mediated
 Idiopathic
 Type 2 diabetes
 Genetic defects of beta-cell function
 Genetic defects of insulin action
 Pancreatic disease
 Excess endogenous production of hormonal antagonists to insulin
 Drug-induced
 Uncommon forms of immune-mediated diabetes
 Associated with genetic syndromes
 Gestational diabetes

8. INVESTIGATIONS
 Urine testing
 Glucose
 Urine testing for glucose- done using dipsticks (common screening procedure)
 To maximize sensitivity, testing is performed on urine passed 1-2 hours after a meal
 Disadvantage- individual variation in renal threshold for glucose.
 Ketones
 Ketonuria is seen during:
• Fasting
• Exercising
• Diet consumption high in fat and low in carbohydrate.
• Not pathognomonic of diabetes. (If associated with glycosuria, the diagnosis of diabetes is high likely)
 Protein
 Standard dipstick testing is done when urinary albumin concentrations are above 300 mg/l
 Specific albumin dipsticks are used when smaller amounts are measured
 Microalbuminuria or proteinuria, in the absence of UTI- indicator of diabetic nephropathy and macrovascular disease.

9.  Blood testing
 Glucose
 Relies on an enzymatic reaction (glucose oxidase)- cheap, automated and highly reliable.
 Colorimetric or other testing sticks- read with a portable electronic meter, used for capillary (finger prick) testing
 Venous plasma values- the most reliable for diagnostic purposes.
 Ketones
 Semi-quantitative
 Difficult to perform
 Retrospective
 Useful in monitoring resolution of DKA in hospitalised patients.
 Glycated haemoglobin
 Glycation- non-enzymatic covalent attachment of glucose to haemoglobin
 Gold standard for long term monitoring
 Most sensitive to changes in glycaemic control in the month
before measurement.

10.  PRESENTING PROBLEMS IN DIABETES
 Hyperglycemia
 Diabetic ketoacidosis
 Hyperglycemic hyperosmolar state
 Hypoglycemia
 Diabetes in pregnancy
 Hyperglycemia in acute myocardial infarction
 Surgery and diabetes

11. 1) HYPERGLYCAEMIA
 Detected on routine biochemical analysis of asymptomatic patients
 Key goals: to establish whether the patient has diabetes, and if so, what type of diabetes it is and how it should be
treated.
 Symptoms
 Thirst, dry mouth
 Polyuria
 Nocturia
 Tiredness, fatigue, lethargy
 Change in weight
 Blurring of vision
 Nausea and headache
 Mood change and irritability

12.  Management of hyperglycemia
 Minimize the risks of long-term microvascular and macrovascular complications.
 Suspected type 1 diabetes- urgent treatment with insulin and prompt referral to a specialist
 Suspected type 2 diabetes- patients to be advised about dietary and lifestyle modifications.
 Educating patients
 Patients should understand their disorder and learn to handle all aspects of management as quickly as possible.
 A structured education can be given by trained educators.
 This is essential if patients are to undertake normal activities safely
 Self-assessment of glycemic control
 Blood glucose testing can be used for self-education, and in acute illness.
 Insulin-treated patients should learn to monitor their blood glucose using capillary blood glucose meters.

13. 2) DIABETIC KETOACIDOSIS (DKA)
 Medical emergency seen principally in people with type 1 diabetes.
 DKA is precipitated when there is failure to increase insulin dose to compensate for the stress response.
 Every patient in DKA is potassium-depleted
 Clinical features
o Symptoms
 Polyuria, thirst
 Weight loss
 Weakness
 Leg cramps
 Blurred vision
o Signs
 Dehydration
 Hypotension
 Cold extremities/ peripheral cyanosis
 Tachycardia
 Smell of acetone and hypothermia

14.  Management of DKA
 Insulin
 Intravenous insulin infusion of 0.1 U/kg body weight/hour is recommended.
 When the blood glucose levels drop, 10% dextrose infusion is introduced
 Insulin infusion is continued to encourage glucose uptake into cells
 Fluid replacement
 Extracellular fluid deficit is corrected with isotonic saline (0.9% sodium chloride).
 If plasma sodium is greater than 155 mmol/l, 0.45% saline may be used initially.
 Potassium
 Treatment with potassium chloride 40 mmol/l is recommended if serum potassium is below 5.5 mmol/l.
 If potassium falls below 3.5 mmol/l, the potassium replacement regimen needs to be reviewed.
 Bicarbonate
 Excessive bicarbonate induces a paradoxical increase in CSF acidosis, that improves oxygen delivery to tissues

15. 3) HYPERGLYCEMIC HYPEROSMOLAR STATE (HHS)
 Characterised by hyperglycaemia, hyperosmolality, and dehydration in absence of ketosis or acidosis.
 Previously referred to as hyperosmolar non-ketonic (HONK) coma.
 Primarily involves Type II diabetics. Increasingly seen in younger adults.
 Precipitating factors- infection, myocardial infarction, cerebrovascular events or drug therapy.
 Principles of management of HHS
 Measure or calculate serum osmolality frequently.
 Fluid replacement with 0.9% sodium chloride (IV).
 Use 0.45% sodium chloride only if osmolality is increasing, despite positive fluid balance.
 Aim for positive fluid balance of 3-6 L by 12 hours,
 Insulin IV infusion of 0.05 U/kg body weight/hour
 Treat coexisting conditions.
 Give prophylactic anticoagulation
 Assume high risk of foot ulceration.

16. 4) HYPOGLYCEMIA
Hypoglycemia results from insulin therapy and from use of oral insulin secretagogues
o Symptoms
 Autonomic
 Sweating
 Trembling and anxiety
 Hunger
 Pounding heart
 Neuroglycopenic
 Confusion and irritability
 Drowsiness
 Speech difficulty
 Incoordination
 Non-specific: Nausea, headache and tiredness

17. o Causes of hypoglycemia
 Missed, delayed or inadequate meal
 Unexpected or unusual exercise
 Alcohol
 Malabsorption
 Lipo-hypertrophy at injection sites causing variable insulin absorption
 Errors in oral anti-diabetic agents or insulin dose administration
o Risk factors for severe hypoglycemia
 Impaired awareness of hypoglycemia
 Age
 Long duration of diabetes
 History of previous severe hypoglycemia
 Renal impairment

18. o Emergency treatment of hypoglycemia
 Mild (self-treated)
 Fast-acting carbohydrate (10-15 g) is taken as glucose drink or tablets, followed by a snack containing complex carbohydrate.
 Severe (external help required)
 If patient is semiconscious or unconscious, parenteral treatment is required:
• IV 75 ml 20% dextrose (0.2 g/kg in children) or
• IM glucagon (1 mg; 0.5 mg in children)
 If patient is conscious and able to swallow:
• Oral refined glucose as drink or sweets (or)
• Apply glucose gel or jam or honey to buccal mucosa
o Prevention of hypoglycemia
 Patient education
 Regular blood glucose monitoring and need to have glucose readily available
 Blood glucose measurement to be done before retiring to bed
 Carbohydrate snack to be taken if the reading is less than 6 mmol/ L.

19. 5) DIABETES IN PREGNANCY
 Maternal glucose metabolism changes to optimize glucose and other nutrient delivery to the fetus.
 Apparent in the second half of pregnancy, when there is an increase in maternal tissue insulin resistance
 Glucose is preferentially supplied to the fetus rather than maternal tissue.
 Gestational diabetes
 Defined as diabetes with first onset or recognition during pregnancy.
 Majority of gestational diabetes develops due to an inability to increase insulin secretion
 Compensates for pregnancy-induced insulin resistance
 Most women can expect to return to normal glucose tolerance immediately after pregnancy.
 Women at high risk should have an OGTT at 24-28 weeks, with guidelines recommending that all are screened by
measuring HbA1C, fasting blood glucose or random blood glucose at the first booking visit.
 HbA1C is unreliable after early pregnancy, when it falls due to increased red cell turnover.

20.  Management of gestational diabetes
 The aim is to normalize the maternal blood glucose and reduce excessive fetal growth.
 The first element of management is dietary modification (reducing quick-acting refined carbohydrate).
 Regular pre- and post-prandial self-monitoring of blood glucose should be done, aiming for pre-meal blood
glucose levels of less than 5.5 mmol/L or post-meal blood glucose levels of less than 7 mmol/L.
 If treatment is necessary, metformin or glibenclamide is considered safe
 Glibenclamide should be used rather than other sulphonyureas because it does not cross the placenta.
 Other oral therapies or injectable incretin-based therapies should not be given in pregnancy.
 Insulin may be required, especially in the later stages of pregnancy.

21. 6) HYPERGLYCEMIA IN ACUTE MYOCARDIAL INFARCTION
 Hyperglycemia is often found in patients who have sustained an acute myocardial infarction.
 In some patients this represents stress hyperglycemia, and few others may have previously
undiagnosed diabetes.
 Many patients with stress hyperglycemia will have impaired glucose tolerance on a
subsequent GTT.
 Hyperglycemia should be treated with insulin in the peri-infarct period, aiming for near-
normalization of blood glucose.
 Good glycemic control using insulin therapy in hyperglycemic patients with acute myocardial
infarction may reduce their long-term mortality from coronary heart disease.

22. 7) SURGERY AND DIABETES
 Surgery causes catabolic stress and secretion of counter-regulatory hormones.
 This increases glycogenolysis, gluconeogenesis, lipolysis, proteolysis and insulin resistance.
 Patients with diabetes have underlying pre-operative morbidity, e.g. cardiovascular disease.
 Careful pre-operative assessment is essential, with the support from diabetes specialist team.
 Pre-operative assessment of patients with diabetes
 Assess glycemic control- surgery to be delayed if HbA1C >75 mmol/mol (>9%)
 Assess cardiovascular status
 Assess foot risk
 Post-operative management
 For patients continuing fasting after surgery, fluid balance and electrolyte levels are to be maintained
 Insulin infusion necessitates dextrose infusion to maintain a supply of glucose.
 IV fluids should include saline and potassium supplementation.
 Use of dextrose or saline (0.45% saline with 5% dextrose and 0.15% potassium chloride) is recommended.

23.  COMPLICATIONS OF DIABETES
 Microvascular/ neuropathic
 Retinopathy, cataract- impaired vision
 Nephropathy- renal failure
 Peripheral neuropathy
• Sensory loss
• Pain
• Motor weakness
 Autonomic neuropathy- GI problems
 Foot disease- Ulceration and arthropathy
 Macrovascular
 Coronal circulation- Myocardial infarction
 Cerebral circulation- Stroke
 Peripheral circulation- Claudication and ischemia

24. MANAGEMENT OF DIABETES MELLITUS
 Ideal management for diabetes allows the person to
• lead a normal life,
• achieve a normal metabolic state
• escape the long-term complications of diabetes.
 Adequate glycemic control is obtained by diet and lifestyle modifications, oral anti-diabetic
medication, and insulin.
 The importance of lifestyle changes such as undertaking regular physical activity, observing a
healthy diet and reducing alcohol consumption should not be underestimated in improving
glycemic control.
 Patients should have access to a dietician at diagnosis, at review and at times of treatment
change.

25.  Dietary management of diabetes
 Aims of dietary management
 Achieve good glycemic control
 Reduce hyperglycemia and avoid hypoglycemia
 Assist with weight management
 Reduce the risk of micro and macrovascular complications
 Ensure adequate nutritional intake
 Avoid ‘atherogenic’ diets or those that aggravate complications.
 Dietary constituents and recommended % of energy intake
 Carbohydrate: 45-60 %
 Fat: < 35%
 Protein: 10-15 %
 Fruit/vegetables: 5 portions daily

26.  Drugs to reduce hyperglycemia
 For many years, there were only a few choices of drugs available for type 2 diabetes- the
biguanide metformin, the sulphonylureas and insulin.
 Insulin is the only treatment for type 1 diabetes.
 Newer drugs for type 2 diabetes include:
 Thiazolidinediones
 Dipeptidyl peptidase 4 (DPP-4) inhibitors
 Glucagon-like peptide 1 (GLP-1) receptor agonists
 Sodium and glucose transporter 2 (SGLT 2) inhibitors.

27.  BIGUANIDES
 Metformin- first-line therapy for type 2 diabetes.
 Used as an adjunct to insulin therapy in obese patients with type 1 diabetes.
 Side-effects are diarrhea, abdominal cramps, bloating and nausea
 Mechanism of action (MOA)
 Classically considered an ‘insulin sensitiser’ because it lowers insulin levels
 Reduces hepatic glucose production
 Has effects on gut glucose uptake and utilisation.
 Clinical use
 Potent blood glucose-lowering treatment.
 Established benefits in microvascular disease.
 Introduced at low dose (500 mg twice daily) to minimise GI side effects.
 Usual maintenance dose is 1 g twice daily.
 Contraindications- patients with impaired hepatic function, alcoholics, in whom lactic acidosis is increased.

28.  SULPHONYLUREAS
 Sulphonyureas are ‘insulin secretagogues’.
 Promotes pancreatic beta-cell insulin secretion.
 MOA of Sulphonylureas
 Acts by closing beta-cell ATP-sensitive K+ channel, decreasing potassium efflux, and triggers insulin secretion.
 Drugs: gliclazide, glibenclamide, glimepiride and glipizide.
 Clinical use
 Used as an add-on to metformin, if glycemia is inadequately controlled on metformin alone.
 Main adverse effects are weight gain and hypoglycemia.
 Hypoglycemia occurs because the closure of potassium channels brings about unregulated insulin secretion, even
with normal or low blood glucose levels.

29.  ALPHA-GLUCOSIDASE INHIBITORS
 Delays carbohydrate absorption in the gut by inhibiting disaccharidases.
 Acarbose and miglitol are available and are taken with each meal.
 Both lower post-brandial blood glucose and can be combined with a sulphonylurea.
 Main side effects are flatulence, abdominal bloating and diarrhea
 THIAZOLIDINEDIONES (TZDs)
 Mechanism of action
 These drugs bind and activate peroxisome proliferator-activated receptor (PPAR)
 PPAR is a nuclear receptor that regulates the expression of several genes involved in metabolism.
 TZDs increase pre-adipocyte differentiation, leading to an increase in fat mass and in body weight.
 Clinical use
 Two most popular TZDs are Rosiglitazone and Pioglitazone.
 Pioglitazone- very effective at lowering blood glucose in insulin-resistant patients.
 May be given with insulin therapy, but combination of insulin and TZDs increases fluid retention and risk of cardiac failure.

30.  INCRETIN-BASED THERAPIES: DPP-4 inhibitors and GLP-1 analogues
 Incretin effect is the augmentation of insulin secretion
 Reflects the release of incretin peptides from the gut.
 The incretin hormones are glucagon-like peptide (GLP-1) and gastric inhibitory polypeptide (GIP).
 The incretin effect has stimulated the development of two incretin-based therapeutic approaches.
 The ‘gliptins’, or DPP-4 inhibitors, enhance concentrations of endogenous GLP-1 and GIP.
 The first DPP-4 inhibitor to market was sitagliptin
 Other available DPP-4 inhibitors include vildagliptin, saxagliptin and linagliptin.
 Currently available GLP-1 receptor agonists include exenatide, exenatide MR and liraglutide.
 Advantage of GLP-1 over the DPP-4 inhibitors- delays gastric emptying, and decreases appetite.
 SGLT2 inhibitors
 SGLT2 is involved in reabsorption of glucose.
 Inhibition results in 25% of filtered glucose not being reabsorbed, with consequent glycosuria.
 Although this helps to lower glucose and results in weight loss, glycosuria leads to increased UTI and genital fungal infections.

31.  INSULIN THERAPY
 Manufacture and formulation
 Until the 1980s, insulin was obtained by extraction and purification from pancreas of cows and pigs.
 Recombinant DNA technology enabled large-scale production of human insulin.
 The duration of action of short-acting, (‘regular’ insulin), can be extended by addition of protamine and zinc at neutral Ph
(isophane or NPH insulin) or excess zinc ions (lente insulins).
 These modified ‘depot’ insulins are cloudy preparations.

32.  Subcutaneous multiple dose insulin therapy
 Insulin is injected subcutaneously into the anterior abdominal, upper arms and outer thighs.
 The rate of absorption may be influenced by site, depth and volume of injection, skin temperature and exercise.
 Unlike soluble insulin, injected 30 minutes before eating, rapid-acting insulin analogues can be administered immediately
before, during or even after meals.
 Long-acting insulin analogues are better able than isophane insulin in maintaining ‘basal’ insulin levels for up to 24 hours
 Insulin dosing regimens
 Most people with type 1 diabetes require two or more injections of insulin daily.
 In type 2 diabetes, insulin is initiated as a once-daily long-acting insulin.
 Initially, 2/3rds of the total daily requirement of insulin is given in the morning in a ratio of short-acting to intermediate-acting
of 1:2, and the remaining third is given in the evening.
 Pre-mixed formulations contain different proportions of soluble and isophane insulins (e.g. 30:70 and 50:50).
 Multiple injection regimens (intensive insulin therapy) are popular, with short-acting insulin being taken before each meal,
and intermediate or long-acting insulin being injected once or twice daily.

33.  Alternative insulin therapies
 ‘Open loop’ systems are battery-powered portable pumps
 Provides continuous subcutaneous intraperitoneal or intravenous infusion of insulin
 In practice, the ‘loop’ is closed by the patient performing blood glucose estimations
 The use of these devices require a high degree of patient motivation.
 Achieves excellent glycemic control. Widespread therapeutic use is limited by cost.
 Clinical trials involving alternative routes of insulin delivery, that includes intrapulmonary (inhalation),
transdermal and oral insulins are ongoing but none has proven commercially viable.

34.  Transplantation
 Whole pancreas transplantation is carried out in a small number of patients with diabetes each year
 Presents problems relating to exocrine pancreatic secretions
 Long-term immunosuppression is necessary.
 At present, the procedure is usually undertaken only in patients with end-stage renal failure who require a
combined pancreas/ kidney transplantation, and in whom diabetes control is difficult.
 Transplantation of isolated pancreatic islets has also been achieved in many centres around the world.
 Drawbacks- transplant rejection, and of destruction by patient’s autoantibodies against beta cells.

35.  ORAL COMPLICATIONS OF DIABETES
 Gingivitis and periodontal disease
 Periapical abscesses
 Salivary gland dysfunction
• Sialosis
• Xerostomia
 Increased incidence of dental caries
 Oral candidiasis and angular stomatitis.
 Burning mouth syndrome
 Circumoral paraesthesia.
 The ‘Grinspan syndrome’ (diabetes, lichen planus and hypertension)

36.  DENTAL THERAPY CONSIDERATIONS
 Type 1 diabetics (prone to DKA)
 Dental treatment modifications considered
 Stress reduction protocol
 Advised normal dietary habits
• Usual insulin dose
• Normal breakfast before dental appointment
 Dental appointment to be scheduled earlier in the day
 Appropriate use of LA
• Minimize post-treatment eating impairment
• Minimizes risk of self-inflicted soft tissue injury
 Insulin dose to be adjusted according to the nature of dental procedure
 Medical consultation is obtained when large doses of insulin is required.
 Type 2 diabetics- Less prone to blood glucose fluctuations
Tolerate all forms of dental treatment, with minimally increased concern

37.  DENTAL THERAPY CONSIDERATIONS cont’d
 Glucose meter to be brought to dental appointments
 If glucose levels are at lower end of normal FBG range (80-120 mg/dl)
• Fast-acting carbohydrate to be taken prior to dental treatment.
 After extensive dental procedures
• Blood glucose levels to be checked more frequently for next few days
 High glucose or ketone levels
• Insulin dose to be changed
• Contact primary care physician
 For a well controlled diabetic patient- No antibiotics required following surgical procedures
 Antibiotic coverage is important in postsurgical period, in conditions of:
• Infection
• Pain
• Stress

38. DM- Dental therapy considerations
ASA Physical status and Classification scale
Optimal physical status classification
for diabetic patients

39.  REFERENCES
1) Davidson’s principles and practice of medicine, 22nd edition.
2) Crispian Scully. Medical problems in dentistry, 6th edition.
3) Stanley. F. Malamed. Medical emergencies in the dental office, 7th edition.