2. Diabetes mellitus: a chronic disease associated with abnormally high levels of the sugar glucose in the blood.
1. Inadequate production of insulin
2. Inadequate sensitivity of cells to the action of insulin.

3. Hyperglycemia is an abnormally high blood glucose (blood sugar) level
Hyperglycemia is an abnormally high blood glucose (blood sugar) level. Hyperglycemia is a hallmark sign of diabetes (both type 1 diabetes and type 2 diabetes) and prediabetes. Diabetes is the most common cause of hyperglycemia.

11. Symptoms and Signs ◾Polyuria ◾Polyipsia ◾Polyphagia ◾Weight loss
◾Muscle weakness
◾Always tired
◾Poor healing
◾Vaginal infection
◾Sexual problems
◾Sensory changes

13. Complication of Diabetes
◾Retinopathy
◾Neuropathy
◾Nephropathy
◾Cardiovascular disease
◾Amputations
◾Other complication

15. How to Control diabetes
◾Change lifestyle.
◾Eating healthier.
◾Exercise (physical activity).
◾Taking care of your body.
◾Taking care of your teeth .
◾taking oral antidiabetic agents.
◾No smoking.
◾ Control blood pressure.
◾Check blood sugar levels daily.
◾Check feet to make sure there is no nerve damage .
◾Check in with you're doctor at least once a month .

17. Diabetes and Dental problems
People with uncontrolled diabetes are at greater risk for dental problems. They're more likely to have infections of their gums and the bones that hold their teeth in place, because diabetes can reduce the blood supply to the gums. High blood sugar may also cause dry mouth and make gum disease.
Note :
the patients with diabetes are higher risk for gum problems .

19. Complications of Diabetes in Oral cavity
◾Tooth decay
◾ Periodontal disease
◾Bleeding gums
◾Tooth sensitivity
◾Recession of gums
◾Bad breath
◾Salivary gland dysfunction

21. Medical Management of DM

23. Treatment of Type 2 Diabetes
Monotherapy with oral agent
Combination therapy with oral agents
Insulin +/- oral agent
insulin required in 20-30% of patients
With duration of the disease, more intensive therapy is required to maintain glycemic goals

24. MAJOR TARGETED SITES OF DRUG CLASSES
Pancreas
Beta-cell dysfunction
Sulfonylureas
Meglitinides
DPP-4 inhibitor
Muscle & fat
Liver
Hepatic glucose overproduction
↓Glucose level
Insulin resistance
Restore normal carbohydrate utilization
Reduce or eliminate acute symptoms
Prevent long-term complications (the ‘opathies)
Gut
Biguanides
Thiazolidinediones
Thiazolidinediones
DPP-4 inhibitors
GLP1 analogue
Insulin
Biguanides
Insulin
Reduced glucose absorption
α-glucosidase inhibitors
Purpose:
To provide a high-level overview of the key mechanisms and target sites for the currently available antihyperglycemic classes.
Takeaway:
Different drug classes with different and complementary mechanisms may be suitable for combination therapy to address multiple pathophysiologies and maximize A1C control.
References
1. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131:281–303.
2. Actos [package insert]. Lincolnshire, Ill: Takeda Pharmaceuticals America, Inc; 2004.
3. Buse JB, Polonsky KS, Burant CF. Type 2 diabetes mellitus. In: Larsen PR et al, eds. Williams Textbook of Endocrinology. 10th ed. Philadelphia: Saunders, 2003:1427–1483.

25. Oral Hypoglycemics Drugs That Increase Insulin Supply:
Sulfanylureas - enhance secretion of insulin from pancreas (requires functional β cells)
First Generation:
Tolbutamide (Orinase)
Acetohexamide (Dymelor)
Tolazamide (Tolinase)
Chlorpropamide (Diabenase)
Second Generation:
Glimipride (Amaryl)
Glyburide (DiaBeta; Micronase)
Glipizide (Glucotrol)
Other Secretagogues
Nateglinide (Starlix)
Repaglinide (Prandin)

26. Mechanism of Insulin Release in the Pancreas

27. Oral Hypoglycemics
Drugs That Decrease Insulin Resistance or Improve Insulin Effectiveness:
Biguanides - decrease glucose secretion by liver and enhance the uptake of glucose in cells
Metformin (Glucophage)
Alpha-Glucosidase Inhibitors - slows uptake of CHO from gut
Acarbose (Precose)
Miglitol (Glyset)
Thiazolidinediones - increases cellular responsiveness to insulin
Pioglitazone (Actos)
Rosiglitazone (Avandia)

28. Mechanism of Insulin Action
Insulin binds to specific high affinity membrane receptors with tyrosine kinase activity
Phosphorylation cascade results in translocation of Glut-4 (and some Glut-1) transport proteins into the plasma membrane.
It induces the transcription of several genes resulting in increased glucose catabolism and inhibits the transcription of genes involved in gluconeogenesis.
Insulin promotes the uptake of K+into cells.

29. Insulin Sensitizers Thiazolidinediones (Glitazones)
These agents are insulin sensitizers, they do not promote insulin secretion from β-cells but insulin is necessary for them to be effective. Pioglitazone and rosigglitazone are the two agents of this group.

30. Oral Drug Therapy for Type 2 DM
Sulfonylureas
Repaglinide
Nateglinide
Biguanides
Thiazolidinediones
Acarbose
Miglitol }
Insulin secretagogues
Insulin sensitizers
Inhibitors of CHO absorption

31. Sulfonylureas: Mechanism of Action
Improved insulin sensitivity from improved glucose control
Chronic treatment with sulfonylureas Þ improved FPG and OGT
These agents stimulate insulin release from the pancreatic islets.
Normalization of glycemia results in increased sensitivity to insulin
Improved glucose control results in increased ß cell responsiveness

32. Sulfonylureas:
Tolbutamide:
Has shorter duration of action.
More safe.

33. Second Generation Sulfonylureas
Glyburide
Oxidized to weakly active metabolites
Half-life - 6 hours
Duration of action-
24 hours
Potency - High
(1.25 to 20 mg/d)

34. Sulfonylureas: Metabolism & Excretion
Metabolized in the liver
Hepatic dysfunction will alter pharmacokinetics
Excretion
Second generation: significant fecal excretion
Glyburide -50%
Glimeperide - 40%

35. Clinical Uses of Sulfonylureas
Hypoglycemic agents for treatment of Type 2 diabetes mellitus
Act by increasing endogenous insulin secretion \ not indicated for Type 1
Most effective when ß cell function has not been severely compromised
Increased insulin secretion favors lipogenesis
Most appropriate in non- or mildly obese
Up to 160 % of ideal body weight

36. Adverse Effects of Sulfonylureas
Severe hypoglycemia
Overdose
Early in treatment
Most common with glyburide
Weight gain
Erythema, skin reactions
Blood dyscrasias (abnormal cellular elements)
Hepatic dysfunction and other GI disturbances

37. Contraindications for Sulfonylureas
Pregnancy
Surgery
Severe infections
Severe stress or trauma
Severe hepatic or renal failure
Insulin therapy should be used in all of these

38. Biguanides Galega officinalis Active ingredient: guanidine
French lilac
Goatsrue
Active ingredient:
guanidine

39. Biguanides First Generation- Phenformin Phenethylbiguanide
Adverse Effects
Lactic acidosis
Risk of cardiovascular disorder

40. Biguanides
Second Generation- Metformin
1,1-Dimethylbiguanide
Rarely produces lactic acidosis except under predisposing conditions

41. Biguanides Mechanism of action:
antihyperglycemic
Correct elevated hepatic glucose output
Inhibit gluconeogenesis
Inhibit glucose-6-phosphatase activity  glycogen sparing
 insulin resistance
Mediated by activation of 5’AMP-activated protein kinase (AMPK)
in hepatocytes and muscle
Do not increase insulin secretion
Not hypoglycemic, even at high doses

42. Second Generation Biguanides
Do not produce hypoglycemia
Secondary beneficial effects on lipids
Reduced triglycerides
Reduced total cholesterol
Reduced LDL
Increased HDL

43. Second Generation Biguanides
Insulin levels unchanged or reduced
Weight loss, some reduction of blood pressure
Appropriate for obese Type 2 diabetics

44. Metformin Excreted unchanged in the urine
Half-life - approximately 2 hours
Does not bind to plasma proteins

45. Metformin Should not be used with renal or hepatic dysfunction
Also approved for prevention of Type 2 diabetes in high risk individuals
Use also for polycystic ovary syndrome: insulin resistance with ovarian hyperandrogenism

46. a glucosidase inhibitors
Mechanism of action:
: competitive and reversible inhibitors of a glucosidase in the small intestine
Delay carbohydrate digestion and absorption
Smaller rise in postprandial glucose

47. a glucosidase inhibitors
Clinical use
For mild to moderate fasting hyperglycemia with significant postprandial hyperglycemia
Taken with the first bite of a meal
Do not produce hypoglycemia, lactic acidosis, or significant weight gain
Effective regardless of age, genetic factors, body weight, duration or severity of disease

48. Dental Management Important to get a complete health history
Ask the undiagnosed diabetic about signs and symptoms, family history, and determine if they are at risk
Ask the known diabetic about their glucose levels, how they control their glucose, their last doctor’s visit, and if they are displaying any symptoms of diabetes now

49. Oral signs and symptoms
Xerostomia, increased caries
Dry atrophic cracked oral mucosa, angular chellitis
Mucositis, ulcers, and desquamative gingivitis, burning mouth syndrome
Difficulty swallowing
Opportunistic bacteria, fungal, viral infection

50. Oral Signs and Symptoms
Poor Wound Healing
Periodontal Disease-usually in poorly controlled or undiagnosed diabetics
Incidence of Perio Disease increases among patients with diabetes as they age
Diabetics with advanced systemic conditions have periodontal disease more frequently and severe.

51. Diagnosing the Diabetic
Symptoms of Diabetes and non-fasting plasma glucose concentration is 200mg/ml or greater
Fasting glucose is 126mg/dl
Lowered oral glucose tolerance test (after 75g glucose load) blood glucose is 200mg/dl or greater

52. Diagnosing the Diabetic
Glycosylated Hemoglobin Hb1Ac
Glycohemoglobin increases in presence of hyperglycemia
Levels help monitor progress of disease and level of patient control
Reflects glucose levels in blood over 6-8 weeks preceding the test

54. Antidiabetics

56. Antidiabetics