Download Hyperglycemia is an abnormally high blood glucose

•
• Diabetes mellitus: a chronic disease associated with
abnormally high levels of the sugar glucose in the blood.
• Diabetes is caused by one of two mechanisms:
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• 1. Inadequate production of insulin
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• 2. Inadequate sensitivity of cells to the action of insulin.
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.
Symptoms and Signs
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◾Polyuria
◾Polyipsia
◾Polyphagia
◾Weight loss
◾Muscle weakness
◾Always tired
◾Poor healing
◾Vaginal infection
◾Sexual problems
◾Sensory changes
Complication of Diabetes
• ◾Retinopathy
• ◾Neuropathy
• ◾Nephropathy
• ◾Cardiovascular disease
• ◾Amputations
• ◾Other complication
How to Control diabetes
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◾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 .
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 .
Complications of Diabetes in
Oral cavity
• ◾Tooth decay
• ◾ Periodontal disease
• ◾Bleeding gums
• ◾Tooth sensitivity
• ◾Recession of gums
• ◾Bad breath
• ◾Salivary gland dysfunction
Medical Management of DM
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
MAJOR TARGETED SITES OF DRUG
CLASSES
Pancreas
Beta-cell dysfunction
Sulfonylureas
Liver
Hepatic glucose
overproduction
Biguanides
•Thiazolidinediones
•DPP-4 inhibitors
•GLP1 analogue
•Insulin
Meglitinides
Muscle & fat
DPP-4 inhibitor
↓Glucose level
Gut
Insulin
resistance
Thiazolidinediones
Biguanides
Reduced
glucose
absorption
α-glucosidase
inhibitors
Insulin
Oral Hypoglycemics
• Drugs That Increase Insulin Supply:
• Sulfanylureas - enhance secretion of insulin from pancreas (requires
functional β cells)
• First Generation:
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Tolbutamide (Orinase)
Acetohexamide (Dymelor)
Tolazamide (Tolinase)
Chlorpropamide (Diabenase)
• Second Generation:
• Glimipride (Amaryl)
• Glyburide (DiaBeta; Micronase)
• Glipizide (Glucotrol)
• Other Secretagogues
• Nateglinide (Starlix)
• Repaglinide (Prandin)
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Mechanism of Insulin Release in the Pancreas
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)
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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.
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.
Oral Drug Therapy for Type 2 DM
• Sulfonylureas
• Repaglinide
Nateglinide
• Biguanides
• Thiazolidinediones
• Acarbose
Miglitol
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Insulin secretagogues
Insulin sensitizers
Inhibitors of CHO
absorption
Sulfonylureas: Mechanism of Action
•Improved insulin sensitivity from improved
glucose control
•Chronic treatment with sulfonylureas 
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
Sulfonylureas:
• Tolbutamide:
• Has shorter duration of action.
• More safe.
Second Generation Sulfonylureas
• Glyburide
• Oxidized to weakly active
metabolites
• Half-life - 6 hours
• Duration of action24 hours
• Potency - High
(1.25 to 20 mg/d)
Sulfonylureas: Metabolism & Excretion
Metabolized in the liver
Hepatic dysfunction will alter
pharmacokinetics
Excretion
Second generation: significant fecal excretion
Glyburide -50%
Glimeperide - 40%
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
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
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
Biguanides
Galega officinalis
French lilac
Goatsrue
Active ingredient:
NH
guanidine
H2N
NH2
Biguanides

First Generation- Phenformin
Phenethylbiguanide
Adverse Effects
Lactic acidosis
Risk of cardiovascular disorder
Biguanides
•
Second Generation- Metformin
1,1-Dimethylbiguanide
CH2H2C
N
H
Rarely produces lactic
acidosis except under
predisposing conditions
NH2
NH2
C
C
N
H
NH2
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
Second Generation Biguanides
• Do not produce hypoglycemia
• Secondary beneficial effects on lipids
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Reduced triglycerides
Reduced total cholesterol
Reduced LDL
Increased HDL
Second Generation Biguanides
• Insulin levels unchanged or reduced
• Weight loss, some reduction of blood pressure
• Appropriate for obese Type 2 diabetics
Metformin
• Excreted unchanged in the urine
• Half-life - approximately 2 hours
• Does not bind to plasma proteins
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
a glucosidase inhibitors
CH2OH
Acarbose
•Mechanism of action:
OH
H3C
•: competitive
and
O reversible inhibitors of
HN
a glucosidase in the
small
CH2intestine
OH
OH
O and
•Delay carbohydrateO digestion
HO
CH2OH
absorption
OH
O
O
OH
•Smaller
HO
OHrise in postprandial glucose
HO
HO
OH
HO
N
OH
Miglitol
HO
HO
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

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
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
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.
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
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