CHAPTER 1

INTRODUCTION

1.1 Background

Indonesian society is a multiple community. On Indonesian society has

developed a variety of assumptions about the various things that continue to develop

from time to time, this assumptions of course assuming its truth value is questionable,

it is still very difficult to distinguish between reality or just a myth. The presumption

of this community extends about various things, without exception dental health

problems. At this time there is a perception in the community around us that if one

tooth on the pull, it will cause the other teeth rocking and eventually will join revoked

as well. This assumption leads people reluctant to have their teeth taken by dentist,

this may in fact may exacerbate their own oral health.In other side, according to the

science of dentistry there are two factor that can cause mobile tooth. They are local

factor and systemic factor.

It is interesting to examine the truth of this assumption, to align public views

on this issue and to find out factors causing tooth rocking actual factor, and explain to

the public the process of mobile tooth.

1.2 Objective

1.2.1 To find the real factor that causing the mobile tooth..

1.2.2 To discover the truth value of the public assumption that says “if one tooth on the pull, it will cause the other teeth rocking and eventually will join revoked as well.”

1.3 Problem

1.3.1 What is cause of mobile tooth?

1.3.2 Is the people assumption that if one tooth on the pull, it will cause the

other teeth rocking and eventually will join revoked as well right?

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1.4 Hypothesis

People assumption that if one tooth on the pull, it will cause the other teeth

rocking and eventually will join revoked as well is wrong.

1.5 Benefits

1.5.1 To be able to know the real factor that cause mobile tooth.

1.5.2 To inform the truth value of the public assumption about mobile tooth.

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CHAPTER 2

GLOSSARY

2.1.Glucose

Glucose (C6H12O6), a simple sugar (monosaccharide), is an important

carbohydrate in biology. Cells use it as a source of energy and a metabolic

intermediate. Glucose is one of the main products of photosynthesis and starts

cellular respiration. Starch and cellulose are polymers derived from the dehydration

of glucose. The name "glucose" comes from the Greek word glukus (γλυκύς),

meaning "sweet." The suffix "-ose" denotes a sugar.

Glucose can adopt several different structures, but all of these structures can

be divided into two families of mirror-images (stereoisomers). Only one set of these

isomers exists in nature, those derived from the "right-handed form" of glucose,

denoted D-glucose. D-glucose is often referred to as dextrose, especially in the food

industry. The term dextrose is derived from dextrorotatory glucose.[2] Solutions of

dextrose rotate polarized light to the right (in Latin: dexter = "right" ). This article

deals with D-glucose. The mirror-image of the molecule, L-glucose, is discussed

separately.

2.1.1. Structure

Although it is called a "simple sugar" (meaning that it is a monosaccharide),

glucose is a complicated molecule because it adopts several different structures.

These structures are usually discussed in the context of the acyclic isomer, which

exists in only minor amounts in solution.

Glucose is derived from hexanal, a chain of six carbon atoms terminating with

an aldehyde group. The other five carbon atoms each bear alcohol groups. Glucose is

called an aldo hexose . In solution, glucose mainly exists as the six-membered ring

containing a hemiacetal group, which arises from the reaction of the hydroxy group at

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C-5 and the aldehyde at C-1. Containing five carbon atoms and one oxygen atom, this

ring is a derivative of pyran. This cyclic form of glucose is called a glucopyranose, of

which two isomers exist.

The asymmetric center at C-1, the site of the hemiacetal, is called the

anomeric carbon atom. The ring closing process can give rise to two isomers, called

anomers, which are labeled α-glucose and β-glucose. These anomers differ in terms

of the relative positioning of the hydroxyl group linked to C-1. When D-glucose is

drawn as a Haworth projection or in the standard chain conformation, the designation

α means that the hydroxyl group attached to C-1 is positioned trans to the -CH2OH

group at C-5, while β means that it is cis. An inaccurate but superficially attractive

alternative method of distinguishing α from β is observing whether the C-1 hydroxyl

is below or above the plane of the ring; this may fail if the glucose ring is drawn

upside down or in an alternative chair conformation. The α and β forms interconvert

over a timescale of hours in aqueous solution, to a final stable ratio of α:β 36:64, in a

process called mutarotation. The ratio would be α:β 11:89 if it were not for the

influence of the anomeric effect.

2.1.2 Commercial

Glucose is produced commercially via the enzymatic hydrolysis of starch.

Many crops can be used as the source of starch. Maize, rice, wheat, cassava, corn

husk and sago are all used in various parts of the world. In the United States,

cornstarch (from maize) is used almost exclusively. Most commercial glucose occurs

as a component of invert sugar, an approximately 1:1 mixture of glucose and

fructose. In principle, cellulose could be hydrolysed to glucose, but this process is not

yet commercially practical.

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2.2 Cardioascular System

The vertebrate cardiovascular system includes a heart, which is a muscular pump

that contracts to propel blood out to the body through arteries, and a series of blood

vessels. The upper chamber of the heart, the atrium (pl. atria), is where the blood

enters the heart. Passing through a valve, blood enters the lower chamber, the

ventricle. Contraction of the ventricle forces blood from the heart through an artery.

The heart muscle is composed of cardiac muscle cells.

Arteries are blood vessels that carry blood away from heart. Arterial walls are

able to expand and contract. Arteries have three layers of thick walls. Smooth muscle

fibers contract, another layer of connective tissue is quite elastic, allowing the arteries

to carry blood under high pressure. A diagram of arterial structure is shown in Figure

3.

Figure 3. Structure of an artery. Image from Purves et al., Life: The Science of

Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman

(www.whfreeman.com), used with permission.

The aorta is the main artery leaving the heart. The pulmonary artery is the

only artery that carries oxygen-poor blood. The pulmonary artery carries

deoxygenated blood to the lungs. In the lungs, gas exchange occurs, carbon dioxide

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diffuses out, oxygen diffuses in. Arterioles are small arteries that connect larger

arteries with capillaries. Small arterioles branch into collections of capillaries known

as capillary beds, an exampe of one is shown in Figure 4.

Figure 4. Structure and blood flow through a vein. The above illustration is from

Figure 5. Capillary with Red Blood Cell (TEM x32,830). This image is copyright

Dennis Kunkel at www.DennisKunkel.com, used with permission.

Capillaries, shown in Figures 4 and 5, are thin-walled blood vessels in which gas

exchange occurs. In the capillary, the wall is only one cell layer thick. Capillaries are

concentrated into capillary beds. Some capillaries have small pores between the cells

of the capillary wall, allowing materials to flow in and out of capillaries as well as the

passage of white blood cells. Changes in blood pressure also occur in the various

vessels of the circulatory system, as shown in Figure 6. Nutrients, wastes, and

hormones are exchanged across the thin walls of capillaries. Capillaries are

microscopic in size, although blushing is one manifestation of blood flow into

capillaries. Control of blood flow into capillary beds is done by nerve-controlled

sphincters.

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Figure 6. Changes in blood pressure, velocity, and the area of the arteries, capillaries,

and veins of the circulatory system. Image from Purves et al., Life: The Science of

Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman

(www.whfreeman.com), used with permission.

The circulatory system functions in the delivery of oxygen, nutrient

molecules, and hormones and the removal of carbon dioxide, ammonia and other

metabolic wastes. Capillaries are the points of exchange between the blood and

surrounding tissues. Materials cross in and out of the capillaries by passing through or

between the cells that line the capillary, as shown in Figure 7.

Figure 7. Capillary structure, and relationships of capillaries to arteries and veins.

Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer

Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with

permission.

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The extensive network of capillaries in the human body is estimated at

between 50,000 and 60,000 miles long. Thoroughfare channels allow blood to bypass

a capillary bed. These channels can open and close by the action of muscles that

control blood flow through the channels, as shown in Figure 8.

Figure 8. Capillary beds and their feeder vessels. Image from Purves et al., Life: The

Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH

Freeman (www.whfreeman.com), used with permission.

Blood leaving the capillary beds flows into a progressively larger series of venules

that in turn join to form veins. Veins carry blood from capillaries to the heart. With the

exception of the pulmonary veins, blood in veins is oxygen-poor. The pulmonary

veins carry oxygenated blood from lungs back to the heart. Venules are smaller veins

that gather blood from capillary beds into veins. Pressure in veins is low, so veins

depend on nearby muscular contractions to move blood along. The veins have valves

that prevent back-flow of blood,

Blood

Plasma is the liquid component of the blood. Mammalian blood consists of a

liquid (plasma) and a number of cellular and cell fragment components as shown in

Figure 21. Plasma is about 60 % of a volume of blood; cells and fragments are 40%.

Plasma has 90% water and 10% dissolved materials including proteins, glucose, ions,

hormones, and gases. It acts as a buffer, maintaining pH near 7.4. Plasma contains

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nutrients, wastes, salts, proteins, etc. Proteins in the blood aid in transport of large

molecules such as cholesterol.

Red blood cells, also known as erythrocytes, are flattened, doubly concave

cells about 7 µm in diameter that carry oxygen associated in the cell's hemoglobin.

Mature erythrocytes lack a nucleus. They are small, 4 to 6 million cells per cubic

millimeter of blood, and have 200 million hemoglobin molecules per cell. Humans

have a total of 25 trillion red blood cells (about 1/3 of all the cells in the body). Red

blood cells are continuously manufactured in red marrow of long bones, ribs, skull,

and vertebrae. Life-span of an erythrocyte is only 120 days, after which they are

destroyed in liver and spleen. Iron from hemoglobin is recovered and reused by red

marrow. The liver degrades the heme units and secretes them as pigment in the bile,

responsible for the color of feces. Each second two million red blood cells are

produced to replace those thus taken out of circulation.

White blood cells, also known as leukocytes, are larger than erythrocytes,

have a nucleus, and lack hemoglobin. They function in the cellular immune response.

White blood cells (leukocytes) are less than 1% of the blood's volume. They are made

from stem cells in bone marrow. There are five types of leukocytes, important

components of the immune system. Neutrophils enter the tissue fluid by squeezing

through capillary walls and phagocytozing foreign substances. Macrophages release

white blood cell growth factors, causing a population increase for white blood cells.

Lymphocytes fight infection. T-cells attack cells containing viruses. B-cells produce

antibodies. Antigen-antibody complexes are phagocytized by a macrophage. White

blood cells can squeeze through pores in the capillaries and fight infectious diseases

in interstitial areas

Platelets result from cell fragmentation and are involved with clotting, as is

shown by Figures 17 and 18. Platelets are cell fragments that bud off megakaryocytes

in bone marrow. They carry chemicals essential to blood clotting. Platelets survive

for 10 days before being removed by the liver and spleen. There are 150,000 to

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300,000 platelets in each milliliter of blood. Platelets stick and adhere to tears in

blood vessels; they also release clotting factors. A hemophiliac's blood cannot clot.

Providing correct proteins (clotting factors) has been a common method of treating

hemophiliacs. It has also led to HIV transmission due to the use of transfusions and

use of contaminated blood products.

2.3. Diabetes Mellitus

Diabetes mellitus is a group of metabolic diseases characterized by high blood

sugar (glucose) levels, that result from defects in insulin secretion, or action, or both.

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Diabetes mellitus, commonly referred to as diabetes (as it will be in this article) was

first identified as a disease associated with "sweet urine," and excessive muscle loss

in the ancient world. Elevated levels of blood glucose (hyperglycemia) lead to

spillage of glucose into the urine, hence the term sweet urine. Normally, blood

glucose levels are tightly controlled by insulin, a hormoneproduced by the pancreas.

Insulin lowers the blood glucose level. When the blood glucose elevates (for

example, after eating food), insulin is released from the pancreas to normalize the

glucose level. In patients with diabetes, the absence or insufficient production of

insulin causes hyperglycemia. Diabetes is a chronic medical condition, meaning that

although it can be controlled, it lasts a lifetime.

2.3.1 The Impact Of Diabetes

Over time, diabetes can lead to blindness, kidney failure, and nerve damage.

These types of damage are the result of damage to small vessels, referred to

as microvascular disease. Diabetes is also an important factor in accelerating the

hardening and narrowing of the arteries (atherosclerosis), leading to strokes, coronary

heart disease, and other large blood vessel diseases. This is referred to

as macrovascular disease. Diabetes affects approximately 17 million people (about

8% of the population) in the United States. In addition, an estimated additional 12

million people in the United States have diabetes and don't even know it.

2.3.2 What causes diabetes?

Insufficient production of insulin (either absolutely or relative to the body's

needs), production of defective insulin (which is uncommon), or the inability of cells

to use insulin properly and efficiently leads to hyperglycemia and diabetes. This latter

condition affects mostly the cells of muscle and fat tissues, and results in a condition

known as "insulin resistance." This is the primary problem in type 2 diabetes. The

absolute lack of insulin, usually secondary to a destructive process affecting the

insulin producing beta cells in the pancreas, is the main disorder in type 1 diabetes. In

type 2 diabetes, there also is a steady decline of beta cells that adds to the process of

elevated blood sugars. Essentially, if someone is resistant to insulin, the body can, to

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some degree, increase production of insulin and overcome the level of resistance.

After time, if production decreases and insulin cannot be released as vigorously,

hyperglycemia develops. Glucose is a simple sugar found in food. Glucose is an

essential nutrient that provides energy for the proper functioning of the body

cells. Carbohydrates are broken down in thesmall intestine and the glucose in

digested food is then absorbed by the intestinal cells into the bloodstream, and is

carried by the bloodstream to all the cells in the body where it is utilized. However,

glucose cannot enter the cells alone and needs insulin to aid in its transport into the

cells. Without insulin, the cells become starved of glucose energy despite the

presence of abundant glucose in the bloodstream. In certain types of diabetes, the

cells' inability to utilize glucose gives rise to the ironic situation of "starvation in the

midst of plenty". The abundant, unutilized glucose is wastefully excreted in the urine.

Insulin Hormon

Insulin is a hormone that is produced by specialized cells (beta cells) of the

pancreas. (The pancreas is a deep-seated organ in the abdomen located behind the

stomach.) In addition to helping glucose enter the cells, insulin is also important in

tightly regulating the level of glucose in the blood. After a meal, the blood glucose

level rises. In response to the increased glucose level, the pancreas normally releases

more insulin into the bloodstream to help glucose enter the cells and lower blood

glucose levels after a meal. When the blood glucose levels are lowered, the insulin

release from the pancreas is turned down. It is important to note that even in the

fasting state there is a low steady release of insulin than fluctuates a bit and helps to

maintain a steady blood sugar level during fasting. In normal individuals, such a

regulatory system helps to keep blood glucose levels in a tightly controlled range. As

outlined above, in patients with diabetes, the insulin is either absent, relatively

insufficient for the body's needs, or not used properly by the body. All of these

factors cause elevated levels of blood glucose (hyperglycemia).

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2.3.3 The different types of diabetes

There are two major types of diabetes, called type 1 and type 2. Type 1

diabetes was also called insulin dependent diabetes mellitus (IDDM), or juvenile

onset diabetes mellitus. In type 1 diabetes, the pancreas undergoes an autoimmune

attack by the body itself, and is rendered incapable of making insulin. Abnormal

antibodies have been found in the majority of patients with type 1 diabetes.

Antibodies are proteins in the blood that are part of the body's immune system. The

patient with type 1 diabetes must rely on insulin medication for survival.

In autoimmune diseases, such as type 1 diabetes, the immune system

mistakenly manufactures antibodies and inflammatory cells that are directed against

and cause damage to patients' own body tissues. In persons with type 1 diabetes, the

beta cells of the pancreas, which are responsible for insulin production, are attacked

by the misdirected immune system. It is believed that the tendency to develop

abnormal antibodies in type 1 diabetes is, in part, genetically inherited, though the

details are not fully understood.

Exposure to certain viral infections (mumpsand Coxsackie viruses) or other

environmental toxins may serve to trigger abnormal antibody responses that cause

damage to the pancreas cells where insulin is made. Some of the antibodies seen in

type 1 diabetes include anti-islet cell antibodies, anti-insulin antibodies and anti-

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glutamic decarboxylase antibodies. These antibodies can be measured in the majority

of patients, and may help determine which individuals are at risk for developing type

1 diabetes.

At present, the American Diabetes Association does not recommend general

screening of the population for type 1 diabetes, though screening of high risk

individuals, such as those with a first degree relative (sibling or parent) with type 1

diabetes should be encouraged. Type 1 diabetes tends to occur in young, lean

individuals, usually before 30 years of age, however, older patients do present with

this form of diabetes on occasion. This subgroup is referred to as latent autoimmune

diabetes in adults (LADA). LADA is a slow, progressive form of type 1 diabetes. Of

all the patients with diabetes, only approximately 10% of the patients have type 1

diabetes and the remaining 90% have type 2 diabetes.

Type 2 diabetes was also referred to as non-insulin dependent diabetes

mellitus (NIDDM), or adult onset diabetes mellitus (AODM). In type 2 diabetes,

patients can still produce insulin, but do so relatively inadequately for their body's

needs, particularly in the face of insulin resistance as discussed above. In many cases

this actually means the pancreas produces larger than normal quantities of insulin. A

major feature of type 2 diabetes is a lack of sensitivity to insulin by the cells of the

body (particularly fat and muscle cells).

In addition to the problems with an increase in insulin resistance, the release

of insulin by the pancreas may also be defective and suboptimal. In fact, there is a

known steady decline in beta cell production of insulin in type 2 diabetes that

contributes to worsening glucose control. (This is a major factor for many patients

with type 2 diabetes who ultimately require insulin therapy.) Finally, the liver in these

patients continues to produce glucose through a process called gluconeogenesis

despite elevated glucose levels. The control of gluconeogenesis becomes

compromised.

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While it is said that type 2 diabetes occurs mostly in individuals over 30 years

old and the incidence increases with age, we are seeing an alarming number patients

with type 2 diabetes who are barely in their teen years. In fact, for the first time in the

history of humans, type 2 diabetes is now more common than type 1 diabetes in

childhood. Most of these cases are a direct result of poor eating habits, higher body

weight, and lack of exercise.

While there is a strong genetic component to developing this form of diabetes,

there are other risk factors - the most significant of which is obesity. There is a direct

relationship between the degree of obesity and the risk of developing type 2 diabetes,

and this holds true in children as well as adults. It is estimated that the chance to

develop diabetes doubles for every 20% increase over desirable body weight.

Regarding age, data shows that for each decade after 40 years of age

regardless of weight there is an increase in incidence of diabetes. The prevalence of

diabetes in persons 65 to 74 years of age is nearly 20%. Type 2 diabetes is also more

common in certain ethnic groups. Compared with a 6% prevalence in Caucasians, the

prevalence in African Americans and Asian Americans is estimated to be 10%, in

Hispanics 15%, and in certain Native American communities 20% to 50%. Finally,

diabetes occurs much more frequently in women with a prior history of diabetes that

develops during pregnancy(gestational diabetes - see below).

Diabetes can occur temporarily during pregnancy. Significant hormonal

changes during pregnancy can lead to blood sugar elevation in genetically

predisposed individuals. Blood sugar elevation during pregnancy is called gestational

diabetes. Gestational diabetes usually resolves once the baby is born. However, 25%-

50% of women with gestational diabetes will eventually develop type 2 diabetes later

in life, especially in those who require insulin during pregnancy and those who

remain overweight after their delivery. Patients with gestational diabetes are usually

asked to undergo an oral glucose tolerance test about six weeks after giving birth to

determine if their diabetes has persisted beyond the pregnancy, or if any evidence

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(such as impaired glucose tolerance) is present that may be a clue to the patient's

future risk for developing diabetes.

"Secondary" diabetes refers to elevated blood sugar levels from another

medical condition. Secondary diabetes may develop when the pancreatic tissue

responsible for the production of insulin is destroyed by disease, such as chronic

pancreatitis(inflammation of the pancreas by toxins like excessive alcohol), trauma,

or surgical removal of the pancreas.

Diabetes can also result from other hormonal disturbances, such as excessive

growth hormone production (acromegaly) and Cushing's syndrome. In acromegaly, a

pituitary gland tumor at the base of the brain causes excessive production of growth

hormone, leading to hyperglycemia. In Cushing's syndrome, the adrenal glands

produce an excess of cortisol, which promotes blood sugar elevation.

In addition, certain medications may worsen diabetes control, or "unmask"

latent diabetes. This is seen most commonly when steroid medications (such

as prednisone) are taken and also with medications used in the treatment of HIV

infection (AIDS).

2.3.4 Diabetes Symptoms

The early symptoms of untreated diabetes are related to elevated blood sugar

levels, and loss of glucose in the urine. High amounts of glucose in the urine can

cause increased urine output and lead to dehydration. Dehydration causes increased

thirst and water consumption. 

The inability of insulin to perform normally has effects on protein, fat and

carbohydrate metabolism. Insulin is an anabolic hormone, that is, one that

encourages storage of fat and protein. 

A relative or absolute insulin deficiency eventually leads to weight loss despite an

increase in appetite. 

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Some untreated diabetes patients also complain of fatigue, nausea and vomiting. 

Patients with diabetes are prone to developing infections of the bladder, skin, and

vaginal areas. 

Fluctuations in blood glucose levels can lead to blurred vision. Extremely elevated

glucose levels can lead to lethargy and coma.

2.3.5 How is diabetes diagnosed?

The fasting blood glucose (sugar) test is the preferred way to diagnose diabetes. It

is easy to perform and convenient. After the person has fasted overnight (at least 8

hours), a single sample of blood is drawn and sent to the laboratory for analysis. This

can also be done accurately in a doctor's office using a glucose meter.

Normal fasting plasma glucose levels are less than 100 milligrams per deciliter

(mg/dl). 

Fasting plasma glucose levels of more than 126 mg/dl on two or more tests on

different days indicate diabetes. 

A random blood glucose test can also be used to diagnose diabetes. A blood

glucose level of 200 mg/dl or higher indicates diabetes.

When fasting blood glucose stays above 100mg/dl, but in the range of 100-

126mg/dl, this is known as impaired fasting glucose (IFG). While patients with IFG

do not have the diagnosis of diabetes, this condition carries with it its own risks and

concerns, and is addressed elsewhere.

2.3.6 The oral glucose tolerance test

Though not routinely used anymore, the oral glucose tolerance test (OGTT) is

a gold standard for making the diagnosis of type 2 diabetes. It is still commonly used

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for diagnosing gestational diabetes and in conditions of pre-diabetes, such

as polycystic ovary syndrome. With an oral glucose tolerance test, the person fasts

overnight (at least eight but not more than 16 hours). Then first, the fasting plasma

glucose is tested. After this test, the person receives 75 grams of glucose (100 grams

for pregnant women). There are several methods employed by obstetricians to do this

test, but the one described here is standard. Usually, the glucose is in a sweet-tasting

liquid that the person drinks. Blood samples are taken at specific intervals to measure

the blood glucose.

For the test to give reliable results:

the person must be in good health (not have any other illnesses, not even a cold).

the person should be normally active (not lying down, for example, as an inpatient

in a hospital), and

the person should not be taking medicines that could affect the blood glucose. 

For three days before the test, the person should have eaten a diet high in

carbohydrates (200-300 grams per day). 

The morning of the test, the person should not smoke or drink coffee.

The classic oral glucose tolerance test measures blood glucose levels five times

over a period of three hours. Some physicians simply get a baseline blood sample

followed by a sample two hours after drinking the glucose solution. In a person

without diabetes, the glucose levels rise and then fall quickly. In someone with

diabetes, glucose levels rise higher than normal and fail to come back down as fast.

People with glucose levels between normal and diabetic have impaired

glucose tolerance (IGT). People with impaired glucose tolerance do not have

diabetes, but are at high risk for progressing to diabetes. Each year, 1%-5% of people

whose test results show impaired glucose tolerance actually eventually develop

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diabetes. Weight loss andexercise may help people with impaired glucose tolerance

return their glucose levels to normal. In addition, some physicians advocate the use of

medications, such as metformin (Glucophage), to help prevent/delay the onset of

overt diabetes.

Recent studies have shown that impaired glucose tolerance itself may be a risk

factorfor the development of heart disease. In the medical community, most

physicians are now understanding that impaired glucose tolerance is nor simply

a precursor of diabetes, but is its own clinical disease entity that requires treatment

and monitoring.

Evaluating the results of the oral glucose tolerance test

Glucose tolerance tests may lead to one of the following diagnoses:

Normal response: A person is said to have a normal response when the 2-hour

glucose level is less than 140 mg/dl, and all values between 0 and 2 hours are less

than 200 mg/dl. 

Impaired glucose tolerance: A person is said to have impaired glucose tolerance

when the fasting plasma glucose is less than 126 mg/dl and the 2-hour glucose

level is between 140 and 199 mg/dl. 

Diabetes: A person has diabetes when two diagnostic tests done on different days

show that the blood glucose level is high. 

Gestational diabetes: A woman has gestational diabetes when she has any two of

the following: a 100g OGTT, a fasting plasma glucose of more than 95 mg/dl, a 1-

hour glucose level of more than 180 mg/dl, a 2-hour glucose level of more than 155

mg/dl, or a 3-hour glucose level of more than 140 mg/dl.

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2.3.7 Why is blood sugar checked at home?

Home blood sugar (glucose) testing is an important part of controlling blood

sugar. One important goal of diabetes treatment is to keep the blood glucose levels

near the normal range of 70 to 120 mg/dl before meals and under 140 mg/dl at two

hours after eating. Blood glucose levels are usually tested before and after meals, and

at bedtime. The blood sugar level is typically determined by pricking a fingertip with

alancing device and applying the blood to a glucose meter, which reads the value.

There are many meters on the market, for example, Accu-Check Advantage, One

Touch Ultra, Sure Step and Freestyle. Each meter has its own advantages and

disadvantages (some use less blood, some have a larger digital readout, some take a

shorter time to give you results, etc). The test results are then used to help patients

make adjustments in medications, diets, and physical activities.

There are some interesting developments in blood glucose monitoring.

Currently, at least three continuous glucose sensors are approved in the United States

(Dexcom, Medtronic and Navigator). The new continuous glucose sensor systems

involve an implantable cannula placed just under the skin in the abdomen or in the

arm. This cannula allows for frequent sampling of blood glucose levels. Attached to

this is a transmitter that sends the data to a pager-like device. This device has a visual

screen that allows the wearer to see, not only the current glucose reading, but also the

graphic trends. In some devices, the rate of change of blood sugar is also shown.

There are alarms for low and high sugar levels. Certain models will alarm if the rate

of change indicates the wearer is at risk for dropping or rising blood glucose too

rapidly. The Medtronic version is specifically designed to interface with their insulin

pumps. However, at this time the patient still must manually approve any insulin dose

(the pump cannot blindly respond to the glucose information it receives, it can only

give a calculated suggestion as to whether the wearer should give insulin, and if so,

how much). All of these devices need to be correlated to fingersticks for a few hours

before they can function independently. The devices can then provide readings for 3-

5 days.

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Diabetes experts feel that these blood glucose monitoring devices give

patients a significant amount of independence to manage their disease process; and

they are a great tool for education as well. It is also important to remember that these

devices can be used intermittently with fingersticks. For example, a well-controlled

patient with diabetes can rely on fingerstick glucose checks a few times a day and do

well. If they become ill, if they decide to embark on a new exercise regimen, if they

change their diet and so on, they can use the sensor to supplement their fingerstick

regimen, providing more information on how they are responding to new lifestyle

changes or stressors. This kind of system takes us one step closer to closing the loop,

and to the development of an artifical pancreas that senses insulin requirements based

on glucose levels and the body's needs and releases insulin accordingly - the ultimate

goal.

2.3.8 Hemoglobin A1c (A1c)

To explain what an hemoglobin A1c is, think in simple terms. Sugar sticks,

and when it's around for a long time, it's harder to get it off. In the body, sugar sticks

too, particularly to proteins. The red blood cells that circulate in the body live for

about three months before they die off. When sugar sticks to these cells, it gives us an

idea of how much sugar is around for the preceding three months. In most labs, the

normal range is 4%-5.9 %. In poorly controlled diabetes, its 8.0% or above, and in

well controlled patients it's less than 7.0% (optimal is <6.5%). The benefits of

measuring A1c is that is gives a more reasonable and stable view of what's happening

over the course of time (three months), and the value does not bounce as much as

finger stick blood sugar measurements. There is a direct correlation between A1c

levels and average blood sugar levels as follows.

While there are no guidelines to use A1c as a screening tool, it gives a

physician a good idea that someone is diabetic if the value is elevated. Right now, it

is used as a standard tool to determine blood sugar control in patients known to have

diabetes. 

21

‘

A1c(%) Mean blood sugar (mg/dl)

6 135

7 170

8 205

9 240

10 275

11 310

12 345

The American Diabetes Association currently recommends an A1c goal of

less than 7.0%. Other Groups such as the American Association of Clinical

Endocrinologists feel that an A1c of <6.5% should be the goal.

Of interest, studies have shown that there is about a 10% decrease in relative

risk formicrovascular disease for every 1% reduction in A1c. So, if a patient starts off

with an A1c of 10.7 and drops to 8.2, though there are not yet at goal, they have

managed to decrease their risk of microvascular complications by about 20%. The

closer to normal the A1c, the lower the absolute risk for microvascular complications.

Data also suggests that the risk of macrovascular disease decreases by about 24% for

every 1% reduction in A1c values.

It should be mentioned here that there are a number of conditions in which an A1c

value may not be accurate. For example, with significant anemia, the red blood cell

count is low, and thus the A1c is altered. This may also be the case in sickle cell

disease and other hemoglobinopathies.

22

1. Severely elevated blood sugar levels due to an actual lack of insulin or a

relative deficiency of insulin.

2. Abnormally low blood sugar levels due to too much insulin or other glucose-

lowering medications.

Insulin is vital to patients with type 1 diabetes - they cannot live with out a source

of exogenous insulin. Without insulin, patients with type 1 diabetes develop severely

elevated blood sugar levels. This leads to increased urine glucose, which in turn leads

to excessive loss of fluid and electrolytes in the urine. Lack of insulin also causes the

inability to store fat and protein along with breakdown of existing fat and protein

stores. This dysregulation, results in the process of ketosis and the release of ketones

into the blood. Ketones turn the blood acidic, a condition called diabetic

ketoacidosis (DKA). Symptoms of diabetic ketoacidosis include nausea, vomiting,

and abdominal pain. Without prompt medical treatment, patients with diabetic

ketoacidosis can rapidly go intoshock, coma, and even death.

Diabetic ketoacidosis can be caused by infections, stress, or trauma all which may

increase insulin requirements. In addition, missing doses of insulin is also an obvious

risk factor for developing diabetic ketoacidosis. Urgent treatment of diabetic

ketoacidosis involves the intravenous administration of fluid, electrolytes, and

insulin, usually in a hospital intensive care unit. Dehydration can be very severe, and

it is not unusual to need to replace 6-7 liters of fluid when a person presents in

diabetic ketoacidosis. Antibiotics are given for infections. With treatment, abnormal

blood sugar levels, ketoneproduction, acidosis, and dehydration can be reversed

rapidly, and patients can recover remarkably well.

In patients with type 2 diabetes, stress, infection, and medications (such as

corticosteroids) can also lead to severely elevated blood sugar levels. Accompanied

by dehydration, severe blood sugar elevation in patients with type 2 diabetes can lead

to an increase in blood osmolality (hyperosmolar state). This condition can lead to

coma (hyperosmolar coma). A hyperosmolar coma usually occurs in elderly patients

23

with type 2 diabetes. Like diabetic ketoacidosis, a hyperosmolar coma is a medical

emergency. Immediate treatment with intravenous fluid and insulin is important in

reversing the hyperosmolar state. Unlike patients with type 1 diabetes, patients with

type 2 diabetes do not generally develop ketoacidosis solely on the basis of their

diabetes. Since in general, type 2 diabetes occurs in an older population, concomitant

medical conditions are more likely to exist, and these patients may actually be sicker

overall. The complication and death rates from hyperosmolar coma is thus higher

than in DKA.

Hypoglycemia means abnormally low blood sugar (glucose). In patients with

diabetes, the most common cause of low blood sugar is excessive use of insulin or

other glucose-lowering medications, to lower the blood sugar level in diabetic

patients in the presence of a delayed or absent meal. When low blood sugar levels

occur because of too much insulin, it is called an insulin reaction. Sometimes, low

blood sugar can be the result of an insufficient caloric intake or sudden excessive

physical exertion.

Blood glucose is essential for the proper functioning of brain cells. Therefore, low

blood sugar can lead to central nervous system symptoms such as

dizziness, confusion, weakness, and tremors.

The actual level of blood sugar at which these symptoms occur varies with each

person, but usually it occurs when blood sugars are less than 65 mg/dl. Untreated,

severely low blood sugar levels can lead to coma, seizures, and, in the worse case

scenario, irreversible brain death. At this point, the brain is suffering from a lack of

sugar, and this usually occurs somewhere around levels of <40 mg/dl.

The treatment of low blood sugar consists of administering a quickly absorbed

glucose source. These include glucose containing drinks, such as orange juice, soft

drinks (not sugar-free), or glucose tablets in doses of 15-20 grams at a time (for

example, the equivalent of half a glass of juice). Even cake frosting applied inside the

24

cheeks can work in a pinch if patient cooperation is difficult. If the individual

becomes unconscious,glucagon can be given by intramuscular injection.

Glucagon causes the release of glucose from the liver (for example, it promotes

gluconeogenesis). Glucagon can be lifesaving and every patient with diabetes who

has a history of hypoglycemia (particularly those on insulin) should have a glucagon

kit. Families and friends of those with diabetes need to be taught how to administer

glucagon, since obviously the patients will not be able to do it themselves in an

emergency situation. Another lifesaving device that should be mentioned is very

simple; a medic alert bracelet should be worn by all patients with diabetes.

2.3.9 The Chronic Complications Of Diabetes

These diabetes complications are related to blood vessel diseases and are

generally classified into small vessel disease, such as those involving the eyes,

kidneys and nerves (microvascular disease), and large vessel disease involving the

heart and blood vessels (macrovascular disease). Diabetes accelerates hardening of

the arteries (atherosclerosis) of the larger blood vessels, leading to coronary heart

disease (angina orheart attack), strokes, and pain in the lower extremities because of

lack of blood supply (claudication).

Eye Complications

The major eye complication of diabetes is called diabetic retinopathy.

Diabetic retinopathy occurs in patients who have had diabetes for at least five years.

Diseased small blood vessels in the back of the eye cause the leakage of protein and

blood in the retina. Disease in these blood vessels also causes the formation of small

aneurysms (microaneurysms), and new but brittle blood vessels (neovascularization).

Spontaneous bleeding from the new and brittle blood vessels can lead

to retinalscarring and retinal detachment, thus impairing vision.

To treat diabetic retinopathy a laser is used to destroy and prevent the

recurrence of the development of these small aneurysms and brittle blood vessels.

Approximately 50% of patients with diabetes will develop some degree of diabetic

25

retinopathy after 10 years of diabetes, and 80% of diabetics have retinopathy after 15

years of the disease. Poor control of blood sugar and blood pressure further

aggravates eye disease in diabetes.

Cataracts and glaucoma are also more common among diabetics. It is also

important to note that since the lens of the eye lets water through, if blood sugar

concentrations vary a lot, the lens of the eye will shrink and swell with fluid

accordingly. As a result, blurry vision is very common in poorly controlled diabetes.

Patients are usually discouraged from getting a new eyeglass prescription until their

blood sugar is controlled. This allows for a more accurate assessment of what kind of

glasses prescription is required.

Kidney damage

Kidney damage from diabetes is called diabetic nephropathy. The onset

of kidney disease and its progression is extremely variable. Initially, diseased small

blood vessels in the kidneys cause the leakage of protein in the urine. Later on, the

kidneys lose their ability to cleanse and filter blood. The accumulation of toxic waste

products in the blood leads to the need for dialysis. Dialysis involves using a machine

that serves the function of the kidney by filtering and cleaning the blood. In patients

who do not want to undergo chronic dialysis, kidney transplantation can be

considered.

The progression of nephropathy in patients can be significantly slowed by

controllinghigh blood pressure, and by aggressively treating high blood sugar levels.

Angiotensin converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor

blockers (ARBs) used in treating high blood pressure may also benefit kidney disease

in diabetic patients.

Nerve damage

Nerve damage from diabetes is called diabetic neuropathy and is also caused

by disease of small blood vessels. In essence, the blood flow to the nerves is limited,

leaving the nerves without blood flow, and they get damaged or die as a result (a term

26

known as ischemia). Symptoms of diabetic nerve damage include numbness, burning,

and aching of the feet and lower extremities. When the nerve disease causes a

complete loss of sensation in the feet, patients may not be aware of injuries to the

feet, and fail to properly protect them. Shoes or other protection should be worn as

much as possible. Seemingly minor skin injuries should be attended to promptly to

avoid serious infections. Because of poor blood circulation, diabetic foot injuries may

not heal. Sometimes, minor foot injuries can lead to serious infection, ulcers, and

even gangrene, necessitating surgical amputation of toes, feet, and other infected

parts.

Diabetic nerve damage can affect the nerves that are important for penile

erection, causing erectile dysfunction (ED, impotence). Erectile dysfunction can also

be caused by poor blood flow to the penis from diabetic blood vessel disease.

Diabetic neuropathy can also affect nerves to the stomach and intestines,

causingnausea, weight loss, diarrhea, and other symptoms of gastroparesis (delayed

emptying of food contents from the stomach into the intestines, due to ineffective

contraction of the stomach muscles).

The pain of diabetic nerve damage may respond to traditional treatments with

gabapentin (Neurontin), phenytoin (Dilantin),

carbamazepine (Tegretol), desipramine (Norpraminine), amitriptyline (Elavil),

or with topically-applied capsaicin (an extract of pepper).

Gabapentin (Neurontin), phenytoin (Dilantin), and carbamazepine (Tegretol)

are medications that are traditionally used in the treatment of seizure disorders.

Amitriptyline (Elavil) and desipramine (Norpraminine) are medications that are

traditionally used for depression. While many of these medications are not FDA

indicated specifically for the treatment of diabetes related nerve pain, they are used

by physicians commonly.

The pain of diabetic nerve damage may also improve with better blood sugar

control, though unfortunately blood glucose control and the course of neuropathy do

27

not always go hand in hand. Newer medications for nerve pain have recently come to

market in the US. Pregabalin (Lyrica) which has an indication for

diabetic neuropathic pain and  duloxetine (Cymbalta) are newer agents used in the

treatment of diabetic neuropathy.

Function

Glucose metabolism and various forms of it in the process.

-Glucose-containing compounds and isomeric forms are digested and taken up by the

body in the intestines, including starch, glycogen, disaccharides and

monosaccharides.

-Glucose is stored in mainly the liver and muscles as glycogen.

-It is distributed and utilized in tissues as free glucose.

Scientists can speculate on the reasons why glucose, and not another

monosaccharide such as fructose (Fru), is so widely used in organisms. One reason

might be that glucose has a lower tendency, relative to other hexose sugars, to react

non-specifically with the amino groups of proteins. This reaction (glycation) reduces

or destroys the function of many enzymes. The low rate of glycation is due to

glucose's preference for the less reactive cyclic isomer. Nevertheless, many of the

28

long-term complications of diabetes (e.g., blindness, renal failure, and peripheral

neuropathy) are probably due to the glycation of proteins or lipids. In contrast,

enzyme-regulated addition of glucose to proteins by glycosylation is often essential to

their function.

2.4.Hyperglycemia

The origin of the term is Greek: hyper-, meaning excessive; -glyc-, meaning

sweet; and -emia, meaning "of the blood"

Hyperglycemia, hyperglycaemia, or high blood sugar is a condition in which an

excessive amount of glucose circulates in the blood plasma. This is generally a

glucose level higher than 10 mmol/l (180 mg/dl), but symptoms may not start to

become noticeable until even higher values such as 15-20 mmol/l (270-360 mg/dl).

However, chronic levels exceeding 7 mmol/l (125 mg/dl) can produce organ damage.

Glucose levels are measured in either:

Milligrams per decilitre (mg/dl), in the United States and other countries (e.g.,

Japan, France, Egypt, Colombia); or

Millimoles per litre (mmol/l), which can be acquired by dividing (mg/dl) by

factor of 18. Scientific journals are moving towards using mmol/l; some journals now

use mmol/l as the primary unit but quote mg/dl in parentheses. Comparatively:

72 mg/dl = 4 mmol/l

90 mg/dl = 5 mmol/l

108 mg/dl = 6 mmol/l

126 mg/dl = 7 mmol/l

144 mg/dl = 8 mmol/l

29

180 mg/dl = 10 mmol/l

270 mg/dl = 15 mmol/l

288 mg/dl = 16 mmol/l

360 mg/dl = 20 mmol/l

396 mg/dl = 22 mmol/l

594 mg/dl = 33 mmol/l

Glucose levels vary before and after meals, and at various times of day; the

definition of "normal" varies among medical professionals. In general, the normal

range for most people (fasting adults) is about 80 to 110 mg/dl or 4 to 6 mmol/l. A

subject with a consistent range above 126 mg/dl or 7 mmol/l is generally held to have

hyperglycemia, whereas a consistent range below 70 mg/dl or 4 mmol/l is considered

hypoglycemic. In fasting adults, blood plasma glucose should not exceed 126 mg/dl

or 7 mmol/l. Sustained higher levels of blood sugar cause damage to the blood vessels

and to the organs they supply, leading to the complications of diabetes.

Chronic hyperglycemia can be measured via the HbA1c test. The definition of

acute hyperglycemia varies by study, with mmol/l levels from 8 to 15.

Temporary hyperglycemia is often benign and asymptomatic. Blood glucose

levels can rise well above normal for significant periods without producing any

permanent effects or symptoms. However, chronic hyperglycemia at levels more than

slightly above normal can produce a very wide variety of serious complications over

a period of years, including kidney damage, neurological damage, cardiovascular

damage, damage to the retina etc.

30

In diabetes mellitus (by far the most common cause of chronic hyperglycemia),

treatment aims at maintaining blood glucose at a level as close to normal as possible,

in order to avoid these serious long-term complications.

Acute hyperglycemia involving glucose levels that are extremely high is a

medical emergency and can rapidly produce serious complications (such as fluid loss

through osmotic diuresis). It is most often seen in persons who have uncontrolled

insulin-dependent diabetes.

The following symptoms may be associated with acute or chronic

hyperglycemia, with the first three comprising the classic hyperglycemic triad:

1. Polyphagia - frequent hunger, especially pronounced hunger

2. Polydipsia - frequent thirst, especially excessive thirst

3. Polyuria - frequent urination, especially excessive urination

4. Blurred vision

5. Fatigue (sleepiness).

6. Weight loss

7. Poor wound healing (cuts, scrapes, etc.)

8. Dry mouth

9. Dry or itchy skin

10. Tingling in feet or heels

11. Impotence (male)

12. Recurrent infections such as vaginal yeast infections, groin rash, or external ear

infections (swimmer's ear)

13. Cardiac arrhythmia

14. Stupor

31

Frequent hunger without other symptoms can also indicate that blood sugar

levels are too low. This may occur when people who have diabetes take too much

oral hypoglycemic medication or insulin for the amount of food they eat. The

resulting drop in blood sugar level to below the normal range prompts a hunger

response. This hunger is not usually as pronounced as in Type I diabetes, especially

the juvenile onset form, but it makes the prescription of oral hypoglycemic

medication difficult to manage.

Polydipsia and polyuria occur when blood glucose levels rise high enough to

result in excretion of excess glucose via the kidneys (glycosuria), producing osmotic

diuresis.

Chronic hyperglycemia that persists even in fasting states is most commonly

caused by diabetes mellitus, and in fact chronic hyperglycemia is the defining

characteristic of the disease. Intermittent hyperglycemia may be present in prediabetic

states. Acute episodes of hyperglycemia without an obvious cause may indicate

developing diabetes or a predisposition to the disorder.

In diabetes mellitus, hyperglycemia is usually caused by low insulin levels

(Diabetes mellitus type 1) and/or by resistance to insulin at the cellular level

(Diabetes mellitus type 2), depending on the type and state of the disease. Low

insulin levels and/or insulin resistance prevent the body from converting glucose into

glycogen (a starch-like source of energy stored mostly in the liver), which in turn

makes it difficult or impossible to remove excess glucose from the blood. With

normal glucose levels, the total amount of glucose in the blood at any given moment

is only enough to provide energy to the body for 20-30 minutes, and so glucose levels

must be precisely maintained by the body's internal control mechanisms. When the

mechanisms fail in a way that allows glucose to rise to abnormal levels,

hyperglycemia is the result.

32

Drugs

Certain medications increase the risk of hyperglycemia, including beta

blockers, epinephrine, thiazide diuretics, corticosteroids, niacin, pentamidine,

protease inhibitors, L-asparaginase,[7] and some antipsychotic agents.[8] The acute

administration of stimulants such as amphetamine typically produces hyperglycemia;

chronic use, however, produces hypoglycemia. Some of the newer, double action

anti-depressants like Zyprexa, and Cymbalta, can also cause significant

hyperglycemia.

Critical illness

A high proportion of patients suffering an acute stress such as stroke or

myocardial infarction may develop hyperglycemia, even in the absence of a diagnosis

of diabetes. Human and animal studies suggest that this is not benign, and that stress-

induced hyperglycemia is associated with a high risk of mortality after both stroke

and myocardial infarction.[9]

Plasma glucose >120 mg/dl in the absence of diabetes is a clinical sign of

sepsis.Physical trauma, surgery and many forms of severe stress can temporarily

increase glucose levels.

Physiological stress

Hyperglycemia occurs naturally during times of infection and inflammation.

When the body is stressed, endogenous catecholamines are released that - amongst

other things - serve to raise the blood glucose levels. The amount of increase varies

from person to person and from inflammatory response to response. As such, no

patient with first-time hyperglycemia should be diagnosed immediately with diabetes

if that patient is concomitantly ill with something else. Further testing, such as a

fasting plasma glucose, random plasma glucose, or two-hour postprandial plasma

glucose level, must be performed.

33

Treatment

Treatment of hyperglycemia requires elimination of the underlying cause, e.g.,

treatment of diabetes when diabetes is the cause. Acute and severe hyperglycemia can

be treated by direct administration of insulin in most cases, under medical

supervision.

2.5. Angiopathy

Angiopathy is the generic term for a disease of the blood vessels

(arteries, veins, and capillaries). The best known and most prevalent

angiopathy is the diabetic angiopathy, a complication that may occur in

chronic diabetes.

2.5.1 Classification

There are two types of angiopathy: macroangiopathy and

microangiopathy. In macroangiopathy, fat and blood clots build up in the

large blood vessels, stick to the vessel walls, and block the flow of blood. In

microangiopathy, the walls of the smaller blood vessels become so thick and

weak that they bleed, leak protein, and slow the flow of blood through the

body. The decrease of blood flow through stenosis or clot formation impair

the flow of oxygen to cells and biological tissues (called ischemia) and lead

to their death (necrosis and gangrene, which in turn may require

amputation). Thus, tissues which are very sensitive to oxygen levels, such as

the retina, develop microangiopathy and may cause blindness (so-called

proliferative diabetic retinopathy). Damage to nerve cells may cause

peripheral neuropathy, and to kidney cells, diabetic nephropathy

(Kimmelstiel-Wilson syndrome).

34

Macroangiopathy, on the other hand, may cause other complications,

such as ischemic heart disease, stroke and peripheral vascular disease which

contributes to the diabetic foot ulcers and the risk of amputation.

2. 5.2 Diabetic Angiopathy

Diabetic angiopathy is a form of angiopathy associated with diabetes

mellitus. While not exclusive, the term is generally an umbrella for the two

most common forms: Diabetic retinopathy and Diabetic nephropathy, whose

pathophysiologies are largely identical.

a. Pathophysiology

Hyperglycemia resulting from diabetes mellitus does not result in a net

increase in intracellular glucose in most cells, as insulin is required for

glucose uptake. However, chronic dysregulated blood glucose in this

condition causes a marked toxicity toward those classes of vascular

endothelium which passively assimilate glucose (i.e. in spite of low insulin),

notably the pericytes of various microvasculatures. Pericytes express enzymes

which convert glucose into osmologically-active metabolites, leading to

apoptosis.

Over time, pericyte death may result in reduced capillary integrity;

subsequently, there is leaking of albumin and other proteins into fluid

compartments. The glomeruli of the kidneys are especially sensitive - see

diabetic nephropathy - where protein leakage caused by late-stage angiopathy

results in diagnostic proteinuria and eventually renal failure. In diabetic

retinopathy the end-result is often blindness due to irreversible retinal damage.

b. Prognosis and Complications

Diabetes mellitus is the most common cause of adult kidney failure

worldwide. It also the most common cause of amputation in the US, usually

toes and feet, often as a result of gangrene, and almost always as a result of

35

peripheral vascular disease. Retinal damage (from microangiopathy) makes it

the most common cause of blindness among non-elderly adults in the US.

Prognosis is generally poor for all forms of Diabetic angiopathy, as

symptomatology is tied to the advancement of the underlying pathology i.e.

the early-stage patient displays either non-specific symptoms or none at all.

"Diabetic dermopathy" is a manifestation of diabetic angiopathy. It is

often found on the shin. There is also Neuropathy; also associated with

diabetes mellitus; type 1 and 2.

2.6. Immunity

Immunity is a biological term that describes a state of having

sufficient biological defenses to avoid infection, disease, or other unwanted

biological invasion. Immunity involves both specific and non-specific

components. The non-specific components act either as barriers or as

eliminators of wide range of pathogens irrespective of antigenic specificity.

Other components of the immune system adapt themselves to each new

disease encountered and are able to generate pathogen-specific immunity.

Adaptive immunity is often sub-divided into two major types

depending on how the immunity was introduced. Naturally acquired immunity

occurs through contact with a disease causing agent, when the contact was not

deliberate, whereas artificially acquired immunity develops only through

deliberate actions such as vaccination. Both naturally and artificially acquired

immunity can be further subdivided depending on whether immunity is

induced in the host or passively transferred from a immune host. Passive

immunity is acquired through transfer of antibodies or activated T-cells from

an immune host, and is short lived -- usually lasting only a few months --

whereas active immunity is induced in the host itself by antigen, and lasts

much longer, sometimes life-long. The diagram below summarizes these

divisions of immunity.

36

A further subdivision of adaptive immunity is characterized by the

cells involved; humoral immunity is the aspect of immunity that is mediated

by secreted antibodies, whereas the protection provided by cell mediated

immunity involves T-lymphocytes alone. Humoral immunity is active when

the organism generates its own antibodies, and passive when antibodies are

transferred between individuals. Similarly, cell mediated immunity is active

when the organisms’ own T-cells are stimulated and passive when T cells

come from another organism.

2.6.1 Passive immunity

Passive immunity is the transfer of active immunity, in the form of

readymade antibodies, from one individual to another. Passive immunity can

occur naturally, when maternal antibodies are transferred to the fetus through

the placenta, and can also be induced artificially, when high levels of human

(or horse) antibodies specific for a pathogen or toxin are transferred to non-

immune individuals. Passive immunization is used when there is a high risk of

infection and insufficient time for the body to develop its own immune

response, or to reduce the symptoms of ongoing or immunosuppressive

diseases.[7] Passive immunity provides immediate protection, but the body

does not develop memory, therefore the patient is at risk of being infected by

the same pathogen later.[8]

a. Naturally acquired passive immunity

Maternal passive immunity is a type of naturally acquired passive

immunity, and refers to antibody-mediated immunity conveyed to a fetus by

its mother during pregnancy. Maternal antibodies (MatAb) are passed through

the placenta to the fetus by an FcRn receptor on placental cells. This occurs

around the third month of gestation.[9] IgG is the only antibody isotype that

can pass through the placenta.[9] Passive immunity is also provided through

the transfer of IgA antibodies found in breast milk that are transferred to the

37

gut of the infant, protecting against bacterial infections, until the newborn can

synthesize its own antibodies.[8]

b. Artificially acquired passive immunity

Artificially acquired passive immunity is a short-term immunization

induced by the transfer of antibodies, which can be administered in several

forms; as human or animal blood plasma, as pooled human immunoglobulin

for intravenous (IVIG) or intramuscular (IG) use, and in the form of

monoclonal antibodies (MAb). Passive transfer is used prophylactically in the

case of immunodeficiency diseases, such as hypogammaglobulinemia.[10] It is

also used in the treatment of several types of acute infection, and to treat

poisoning.[7] Immunity derived from passive immunization lasts for only a

short period of time, and there is also a potential risk for hypersensitivity

reactions, and serum sickness, especially from gamma globulin of non-human

origin.[8]

The artificial induction of passive immunity has been used for over a

century to treat infectious disease, and prior to the advent of antibiotics, was

often the only specific treatment for certain infections. Immunoglobulin

therapy continued to be a first line therapy in the treatment of severe

respiratory diseases until the 1930’s, even after sulfonamide antibiotics were

introduced.[10]

c. Passive transfer of cell-mediated immunity

Passive or "adoptive transfer" of cell-mediated immunity, is conferred

by the transfer of "sensitized" or activated T-cells from one individual into

another. It is rarely used in humans because it requires histocompatible

(matched) donors, which are often difficult to find. In unmatched donors this

type of transfer carries severe risks of graft versus host disease.[7] It has,

however, been used to treat certain diseases including some types of cancer

and immunodeficiency. This type of transfer differs from a bone marrow

38

transplant, in which (undifferentiated) hematopoietic stem cells are

transferred.

2.6.2. Active immunity

Picture 2. The time course of an immune response. Due to the formation of

immunological memory, reinfection at later time points leads to a rapid increase in

antibody production and effector T cell activity. These later infections can be mild or

even inapparent.

The time course of an immune response. Due to the formation of

immunological memory, reinfection at later time points leads to a rapid

increase in antibody production and effector T cell activity. These later

infections can be mild or even inapparent.

When B cells and T cells are activated by a pathogen, memory B-cells

and T- cells develop. Throughout the lifetime of an animal these memory cells

will “remember” each specific pathogen encountered, and are able to mount a

strong response if the pathogen is detected again. This type of immunity is

both active and adaptive because the body's immune system prepares itself for

future challenges. Active immunity often involves both the cell-mediated and

humoral aspects of immunity as well as input from the innate immune system.

The innate system is present from birth and protects an individual from

39

pathogens regardless of experiences, whereas adaptive immunity arises only

after an infection or immunization and hence is "acquired" during life.

a. Naturally acquired active immunity

Naturally acquired active immunity occurs when a person is exposed

to a live pathogen, and develops a primary immune response, which leads to

immunological memory.[7] This type of immunity is “natural” because it is not

induced by deliberate exposure. Many disorders of immune system function

can affect the formation of active immunity such as immunodeficiency (both

acquired and congenital forms) and immunosuppression.

b. Artificially acquired active immunity

Artificially acquired active immunity can be induced by a vaccine, a

substance that contains antigen. A vaccine stimulates a primary response

against the antigen without causing symptoms of the disease.[7] The term

vaccination was coined by Edward Jenner and adapted by Louis Pasteur for

his pioneering work in vaccination. The method Pasteur used entailed treating

the infectious agents for those diseases so they lost the ability to cause serious

disease. Pasteur adopted the name vaccine as a generic term in honor of

Jenner's discovery, which Pasteur's work built upon.

There are four types of traditional vaccines:

Inactivated vaccines are composed of micro-organisms that have been killed

with chemicals and/or heat and are no longer infectious. Examples are

vaccines against flu, cholera, bubonic plague, and hepatitis A. Most

vaccines of this type are likely to require booster shots.

Live, attenuated vaccines are composed of micro-organisms that have been

cultivated under conditions which disable their ability to induce disease.

These responses are more durable and do not generally require booster

shots. Examples include yellow fever, measles, rubella, and mumps.

Toxoids are inactivated toxic compounds from micro-organisms in cases

where these (rather than the micro-organism itself) cause illness, used prior

40

to an encounter with the toxin of the micro-organism. Examples of toxoid-

based vaccines include tetanus and diphtheria.

Subunit -vaccines are composed of small fragments of disease causing

organisms. A characteristic example is the subunit vaccine against

Hepatitis B virus.

Most vaccines are given by hypodermic injection as they are not

absorbed reliably through the gut. Live attenuated Polio and some Typhoid

and Cholera vaccines are given orally in order to produce immunity based in

the bowel.

2.7. Collagen

Collagen is a group of naturally occurring proteins. In nature, it is

found exclusively in animals, especially in the flesh and connective tissues of

mammals.[1] It is the main component of connective tissue, and is the most

abundant protein in mammals,[2] making up about 25% to 35% of the whole-

body protein content. Collagen, in the form of elongated fibrils, is mostly

found in fibrous tissues such as tendon, ligament and skin, and is also

abundant in cornea, cartilage, bone, blood vessels, the gut, and intervertebral

disc.

In muscle tissue it serves as a major component of endomysium. Collagen

constitutes 1% to 2% of muscle tissue, and accounts for 6% of the weight of

strong, tendinous muscles.[3] Gelatin, which is used in food and industry, is

collagen that has been irreversibly hydrolyzed.

2.7.1 Molecular Structure

The tropocollagen or "collagen molecule" is a subunit of larger

collagen aggregates such as fibrils. It is approximately 300 nm long and

1.5 nm in diameter, made up of three polypeptide strands (called alpha

chains), each possessing the conformation of a left-handed helix (its name is

41

not to be confused with the commonly occurring alpha helix, a right-handed

structure). These three left-handed helices are twisted together into a right-

handed coiled coil, a triple helix or "super helix", a cooperative quaternary

structure stabilized by numerous hydrogen bonds. With type I collagen and

possibly all fibrillar collagens if not all collagens, each triple-helix associates

into a right-handed super-super-coil that is referred to as the collagen

microfibril. Each microfibril is interdigitated with its neighboring microfibrils

to a degree that might suggest that they are individually unstable although

within collagen fibrils they are so well ordered as to be crystalline.

A distinctive feature of collagen is the regular arrangement of amino

acids in each of the three chains of these collagen subunits. The sequence

often follows the pattern Gly-Pro-X or Gly-X-Hyp, where X may be any of

various other amino acid residues. Proline or hydroxyproline constitute about

1/6 of the total sequence. With glycine accounting for the 1/3 of the sequence,

this means that approximately half of the collagen sequence is not glycine,

proline or hydroxyproline, a fact often missed due to the distraction of the

unusual GX1X2 character of collagen alpha-peptides. This kind of regular

repetition and high glycine content is found in only a few other fibrous

proteins, such as silk fibroin. About 75-80% of silk is (approximately) -Gly-

Ala-Gly-Ala- with 10% serine, and elastin is rich in glycine, proline, and

alanine (Ala), whose side group is a small, inert methyl group. Such high

glycine and regular repetitions are never found in globular proteins save for

very short sections of their sequence. Chemically-reactive side groups are not

needed in structural proteins as they are in enzymes and transport proteins,

however collagen is not quite just a structural protein. Due to its key role in

the determination of cell phenotype, cell adhesion, tissue regulation and

infrastructure, many sections of its non-proline rich regions have cell or

matrix association / regulation roles. The relatively high content of proline

and hydroxyproline rings, with their geometrically constrained carboxyl and

(secondary) amino groups, along with the rich abundance of glycine, accounts

42

for the tendency of the individual polypeptide strands to form left-handed

helices spontaneously, without any intrachain hydrogen bonding.

Because glycine is the smallest amino acid with no side chain, it plays

a unique role in fibrous structural proteins. In collagen, Gly is required at

every third position because the assembly of the triple helix puts this residue

at the interior (axis) of the helix, where there is no space for a larger side

group than glycine’s single hydrogen atom. For the same reason, the rings of

the Pro and Hyp must point outward. These two amino acids help stabilize the

triple helix—Hyp even more so than Pro; a lower concentration of them is

required in animals such as fish, whose body temperatures are lower than

most warm-blooded animals.

2.7.2 Fibriliar Structure

The tropocollagen subunits spontaneously self-assemble, with

regularly staggered ends, into even larger arrays in the extracellular spaces of

tissues.[22][23] In the fibrillar collagens, the molecules are staggered from each

other by about 67 nm (a unit that is referred to as ‘D’ and changes depending

upon the hydration state of the aggregate). Each D-period contains 4 and a

fraction collagen molecules. This is because 300 nm divided by 67 nm does

not give an integer (the length of the collagen molecule divided by the stagger

distance D). Therefore in each D-period repeat of the microfibril, there is a

part containing five molecules in cross-section—called the “overlap” and a

part containing only 4 molecules, called the "gap". The triple-helices are also

arranged in a hexagonal or quasi-hexagonal array in cross-section, in both the

gap and overlap regions.

There is some covalent crosslinking within the triple helices, and a

variable amount of covalent crosslinking between tropocollagen helices

forming well organized aggregates (such as fibrils). Larger fibrillar bundles

are formed with the aid of several different classes of proteins (including

different collagen types), glycoproteins and proteoglycans to form the

43

different types of mature tissues from alternate combinations of the same key

players.[23] Collagen's insolubility was a barrier to the study of monomeric

collagen until it was found that tropocollagen from young animals can be

extracted because it is not yet fully crosslinked. However, advances in

microscopy techniques electron microscopy (EM) and atomic force

microscopy (AFM)) and X-ray diffraction have enabled researchers to obtain

increasingly detailed images of collagen structure in situ. These later advances

are particularly important to better understanding the way in which collagen

structure affects cell-cell and cell-matrix communication, and how tissues are

constructed in growth and repair, and changed in development and disease.

Collagen fibrils are semicrystalline aggregates of collagen molecules.

Collagen fibers are bundles of fibrils.

Collagen fibrils/aggregates are arranged in different combinations and

concentrations in various tissues to provide varying tissue properties. In bone,

entire collagen triple helices lie in a parallel, staggered array. Forty nm gaps

between the ends of the tropocollagen subunits (approximately equal to the

gap region) probably serve as nucleation sites for the deposition of long, hard,

fine crystals of the mineral component, which is (approximately)

hydroxyapatite, Ca10(PO4)6(OH)2 with some phosphate. It is in this way that

certain kinds of cartilage turn into bone. Type I collagen gives bone its tensile

strength.

2.7.4 Types and associated disorders

Collagen occurs in many places throughout the body. So far, 29 types

of collagen have been identified and described. Over 90% of the collagen in

the body, however, is of type I, II, III, and IV.

Collagen One: skin, tendon, vascular, ligature, organs, bone (main

component of bone)

Collagen Two: cartilage (main component of cartilage)

44

Collagen Three: reticulate (main component of reticular fibers),

commonly found alongside type I.

Collagen Four: forms bases of cell basement membrane

Collagen Five: cells surfaces, hair and placenta

Collagen-related diseases most commonly arise from genetic defects

or nutritional deficiencies that affect the biosynthesis, assembly,

postranslational modification, secretion, or other processes involved in normal

collagen production.

2.7.5 Use of Collagen

Collagen is one of the long, fibrous structural proteins whose functions

are quite different from those of globular proteins such as enzymes. Tough

bundles of collagen called collagen fibers are a major component of the

extracellular matrix that supports most tissues and gives cells structure from

the outside, but collagen is also found inside certain cells. Collagen has great

tensile strength, and is the main component of fascia, cartilage, ligaments,

tendons, bone and skin.[30][31] Along with soft keratin, it is responsible for skin

strength and elasticity, and its degradation leads to wrinkles that accompany

ageing. It strengthens blood vessels and plays a role in tissue development. It

is present in the cornea and lens of the eye in crystalline form. It is also used

in cosmetic surgery and burns surgery. Hydrolyzed collagen can play an

important role in weight management, as a protein, it can be advantageously

used for its satiating power

a. Industrial uses

If collagen is sufficiently denatured, e.g. by heating, the three

tropocollagen strands separate partially or completely into globular domains,

containing a different secondary structure to the normal collagen polyproline

II (PPII), e.g. random coils. This process describes the formation of gelatin,

which is used in many foods, including flavored gelatin desserts. Besides

food, gelatin has been used in pharmaceutical, cosmetic, and photography

45

industries.[32] From a nutritional point of view, collagen and gelatin are a poor-

quality sole source of protein since they do not contain all the essential amino

acids in the proportions that the human body requires—they are not 'complete

proteins' (as defined by food science, not that they are partially structured).

Manufacturers of collagen-based dietary supplements claim that their products

can improve skin and fingernail quality as well as joint health. However,

mainstream scientific research has not shown strong evidence to support these

claims.[citation needed] Individuals with problems in these areas are more likely to

be suffering from some other underlying condition (such as normal aging, dry

skin, arthritis etc.) rather than just a protein deficiency.

From the Greek for glue, kolla, the word collagen means "glue

producer" and refers to the early process of boiling the skin and sinews of

horses and other animals to obtain glue. Collagen adhesive was used by

Egyptians about 4,000 years ago, and Native Americans used it in bows about

1,500 years ago. The oldest glue in the world, carbon-dated as more than

8,000 years old, was found to be collagen—used as a protective lining on rope

baskets and embroidered fabrics, and to hold utensils together; also in

crisscross decorations on human skulls.[33] Collagen normally converts to

gelatin, but survived due to the dry conditions. Animal glues are

thermoplastic, softening again upon reheating, and so they are still used in

making musical instruments such as fine violins and guitars, which may have

to be reopened for repairs—an application incompatible with tough, synthetic

plastic adhesives, which are permanent. Animal sinews and skins, including

leather, have been used to make useful articles for millennia.

Gelatin-resorcinol-formaldehyde glue (and with formaldehyde

replaced by less-toxic pentanedial and ethanedial) has been used to repair

experimental incisions in rabbit lungs.[34]

46

b. Medical uses

The cardiac valve rings, the central body and the cardiac skeleton of the

heart summarily represent a unique and moving collagen anchor to the fluid

mechanics of the heart. Individual valvular leaflets are arguably held in shape

by collagen under great extremes of pressure. Calcium deposition within

collagen occurs as a natural consequence of aging. These fixed points in an

otherwise moving display of blood and muscle enable current cardiac imaging

technology to arrive at ratios essentially stating blood in cardiac input and

blood out cardiac output. Specified imaging such as calcium scoring illustrates

the utility of this methodology, especially in an aging patient subject to

pathology of the collagen underpinning.

Collagen has been widely used in cosmetic surgery, as a healing aid

for burn patients for reconstruction of bone and a wide variety of dental,

orthopedic and surgical purposes. Some points of interest are:

1. when used cosmetically, there is a chance of allergic reactions causing

prolonged redness; however, this can be virtually eliminated by simple

and inconspicuous patch testing prior to cosmetic use, and

2. most medical collagen is derived from young beef cattle (bovine) from

certified BSE (Bovine spongiform encephalopathy) free animals. Most

manufacturers use donor animals from either "closed herds", or from

countries which have never had a reported case of BSE such as Australia,

Brazil and New Zealand.

3. porcine (pig) tissue is also widely used for producing collagen sheet for a

variety of surgical purposes.

4. alternatives using the patient's own fat, hyaluronic acid or polyacrylamide

gel are readily available.

Collagens are widely employed in the construction of artificial skin

substitutes used in the management of severe burns. These collagens may be

derived from bovine, equine or porcine, and even human, sources and are

47

sometimes used in combination with silicones, glycosaminoglycans,

fibroblasts, growth factors and other substances.

Collagen is also sold commercially as a joint mobility supplement.[35]

Because proteins are broken down into amino acids before absorption, there is

no reason for orally ingested collagen to affect connective tissue in the body,

except through the effect of individual amino acid supplementation.

Recently an alternative to animal-derived collagen has become

available. Although expensive, this human collagen, derived from donor

cadavers, placentas and aborted fetuses, may minimize the possibility of

immune reactions.

Although it cannot be absorbed through the skin, collagen is now

being used as a main ingredient for some cosmetic makeup.[36]

Collagen is also frequently used in scientific research applications for

cell culture, studying cell behavior and cellular interactions with the

extracellular environment. Suppliers such as Trevigen manufacture rat and

bovine Collagen I and mouse Collagen IV.

2.8. Strepptococcus Mutans

Clark in 1924 isolated this particular streptococcus and named it as S. mutans

due to its varying morphological nature. S.mutans are gram positive, non-motile,

catalase-negative cocci. It synthesizes insoluble polysaccharide from sucrose that is

regarded as an important characteristic contributing to the caries inducing properties

of S. mutans. These can colonize on tooth surfaces and dentures. S. mutans have

specific receptor sites known as adhesins on its cell surface that attach to acquired

enamel pellicle through adhesion promoting proteins found in saliva that help to

facilitate the adhesion of S. mutans to the acquired pellicle. Human salivary

concentrations of S. mutans range from undetectable to 106 - 107 CFU/ml (colony

forming units). S. mutans are more aciduric than other streptococci and be cultured in

a media at a pH as low as 4.3.

48

Currently seven distinct species of human and animal mutans streptococcus and

eight serotypes (a-h) are recognized based on the antigenic specificity of cell wall

carbohydrates. Human serotypes are limited to three namely c, e and f. These can be

cultured in blood agar and can be seen as alpha hemolytic cocci in chains. Listed

below are properties related to cariogenicity of S. mutans.

• The samples can be isolated from tooth surfaces before the development of

caries.

• The samples produce water soluble and insoluble extracellular polysaccharide from

sucrose which helps in the colonization of tooth surfaces by consolidating

microbial attachment.

• S. mutans have the ability to initiate and maintain microbial growth, metabolism and

acid production in sites with a low pH. S. mutans have the ability to transport sugars

rapidly in competition with other plaque bacteria even at low pH.

• S. mutans have an efficient rapid metabolism of sugars to lactic and other organic

acids.

• S. mutans are acidogenic and aciduric in nature.

• The samples can attain the critical pH for enamel demineralization more rapidly

than other common plaque bacteria.

• S. mutans produces intracellular polysaccharide which acts as a food reservoir

during low concentration of dietary carbohydrates.

2.9. Plaque

Dental plaque can be defined as a diverse community of micro-organisms found

on the tooth surface as a biofilm, embedded in an extracellular matrix of polymers of

host and microbial origin. The complex and diverse oral microflora consists of a wide

range of species of bacteria, viruses, mycoplasmas and yeasts. Various groups of

gram positive bacteria such as streptococcus, staphylococcus, actinomyces,

lactobacillus, eubacterium and gram negative bacteria like neisseria, veillonella,

porphyromonas, prevotella, fusobacterium, spirochaetes that are found in the oral

49

cavity including the dental plaque. The formation of plaque can be divided into three

stages namely initial colonization, rapid bacterial growth and remodeling phase.

Bacterial plaque seem to be most consistent one factor in the etiology of

gingivitis and periodontitis. When we consider plaque as a small world of

microorganisms, a microcosm, it is easy to understand the effect it has on the gingival

tissues. This organized mass of bacteria is glued to the tooth surface near and under

the gingival margin. As it extend into the sulcus, many of products of microcosm are

in intimate contact with the sulcural epithelial lining. Since these products differ, they

have different effect on the gingiva. The most important products of microcosm are

enzymes, endotoxins, and protein breakdown product.

There is evidence that as the enzymes are produced by bacteria, they act on the

sulcular lining to loosen the epithelial cells. The mucopolysaccharide substance

between the cells tends to break down and “leakage” occurs from the crevice into the

underlying connective tissue. The substances that leak through seem to be the

endotoxins and protein breakdown products. Recent studies have shown that the

possibility exists that the endotoxins are capable of establishing an inflammatory

reaction within the gingiva on an immunologic or allergic basis (Ranney and Zander,

1970; Horton, 1973). On the other hand, protein breakdown product such as hydrogen

sulphide, indole and skatole are most irritating and are capable of setting up the type

of inflammatory reaction we seen gingivitis and periodontitis (Frostell, 1969)

The human body is naturally colonised by a diverse array of micro-organisms

whose metabolic activity is important for human physiology and health. Most studies

that assess the functional potentials and controls of these complex communities rely

on: (i) the characterisation of individual isolates or enrichments, (ii) quantification of

micro-organisms that are thought to mediate a certain process, or (iii) metagenomic

analysis of a certain body region. Established methods of microbial ecology that

allow the direct measurement of metabolic conversions in natural microbial samples

from humans under different experimental conditions, such as incubation with

isotopically-labelled substrates, dye probes for specific compounds combined with

50

microscopy or electrochemical microsensors, are rarely reported. However, different

microbial pathways, including fermentation, sulfate reduction, methanogenesis and

acetogenesis, have been proposed to occur in humans. Surprisingly, denitrification

(the respiratory reduction of nitrate (NO3-) or nitrite (NO2

-) via nitric oxide (NO) to

nitrous oxide (N2O) or dinitrogen (N2) is believed to be insignificant in human-

associated microbial communities, even though NO3- and NO2

- co-occur in significant

concentrations with micro-organisms in various body regions, such as the human oral

cavity.

Denitrification is performed by facultative anaerobic micro-organisms and is

coupled to the oxidation of reduced organic carbon or reduced inorganic compounds,

such as ferrous iron, hydrogen sulfide or hydrogen. The reductive sequence (NO3- >

NO2- > NO > N2O > N2) of denitrification is mediated by periplasmic and membrane-

bound enzymes specific for each step. The most important genes for the detection of

denitrification in complex microbial samples are narG for NO3- reductase, nirS and

nirK for NO2- reductases, qnorB or cnorB for NO reductases, and nosZ for N2O

reductase. Denitrifying bacteria release NO or N2O as intermediates during metabolic

activity in pure culture and in complex microbial communities, such as soils, nitrogen

cycling biofilms and ingested bacteria within different invertebrates guts.

Notably, human saliva contains NO3- concentrations in the millimolar range,

because dietary NO3- is concentrated in salivary glands after it is absorbed from the

intestine into the blood. Thus, the human-associated microbial biofilm community of

dental plaque and bacteria that cover other oral surfaces are exposed to NO3-.

However, investigations of plaque metabolism have focused on aerobic respiration

and acid fermentation of carbohydrates. Experiments with rat tongues as well as tooth

and other surfaces in the human mouth have shown that salivary NO3- can be

converted by oral micro-organisms to NO2-, explaining the presence of NO2

- in

addition to NO3- in saliva. Detection of NO in air incubated in the human mouth has

led to the hypothesis that bacterially-derived salivary NO2- is chemically reduced to

NO in acidic microenvironments in the oral cavity. The underlying processes have

51

never been directly demonstrated because NO could not be measured in dental

biofilms over relevant spatial scales. Therefore, other investigators considered NO2- in

human saliva a stable oxidation product of NO synthase-derived NO that is produced

by gingival cells to regulate the gum immune and vascular systems.

Due to the possible formation of NO, plaque nitrogen metabolism might be important

to dental health. Dental plaque causes periodontal diseases and dental caries, affecting

almost every human being. As an inflammatory disorder of gum tissue surrounding

the teeth, periodontal diseases might be especially affected by nitrogen metabolism of

dental plaque, if NO is generated as a side product at the gum-plaque interface. NO

plays a complex, but not well understood role in periodontal diseases. NO, at low

concentrations, is an important signalling molecule that coordinates functions of

immune system cells that are involved in inflammatory processes. Bacterial

lipopolysaccharides stimulate production of proinflammatory cytokines, which

induce production of high, cytotoxic NO concentrations by certain immune system

cells. Furthermore, high NO levels during inflammation induce expression of matrix

metalloproteinases in neutrophiles, which mediate soft tissue degradation.

Besides its potential importance to dental health, oral nitrogen metabolism is

important for human physiology. The formation of NO2- as a denitrification

intermediate by oral micro-organisms leads to chemical conversion of NO2- to NO in

the acidic stomach, acting as an antimicrobial agent against pathogenic bacteria and

stimulating gastric blood flow. Moreover, NO2- is absorbed into plasma, where it

serves as a NO source for the regulation of vasodilatation under hypoxic conditions.

It is still unclear whether microbial nitrogen metabolism in human dental plaque is

significant in comparison to other oral surfaces.

In the present study, we hypothesise that dental plaque represents a habitat for

microbial denitrification in humans, driving the biological conversion of salivary

NO3- to the denitrification intermediates NO and N2O, and to the final product N2. We

use direct microbial ecology methods, including a recently developed NO

microsensor, to demonstrate in situ NO formation during denitrification in dental

52

plaque and to show that NO is formed at concentrations that are significant for

signalling to host tissue. In addition, we aim to show the in vivo significance of

plaque denitrification for the formation of denitrification intermediates by correlating

the oral accumulation of N2O in humans to salivary NO3-/NO2

- concentrations and to

the presence of plaque.

2.10. Calculus

Calculus is closely related to bacterial plaque in as much as the plaque is the

matrix in which the calcium and phosphorus salt are deposited. While it has been

shown that bacteria are not essential to calculus formation (Baer ad Newton, 1960),

microorganisms are always present in human supragingival and subgingival calculus.

Calculus is interesting in that it is both a mechanical and a bacterial irritant. Because

of the hard, crusty surface, calculus irritates the gingival tissues by physical

irritations. More significant, however, are the bacteria that form part of the matrix and

surround the calcified surface. The irritation an etiologic agent in periodontal disease.

2.11. Peridontitis

Periodontitis could be defined as a disorder of supporting structures of teeth,

including the gingiva, periodontal ligament and alveolar bone. Periodontitis and all

periodontal diseases are bacterial infections that destroy the attachment fibers and

supporting bone that hold the teeth in the mouth. Left untreated, these diseases can

lead to tooth loss. The main cause of periodontal disease is a bacterial plaque, a

sticky, colorless film that constantly forms on teeth.

Inflammation or infection of the gums is called gingivitis. If allowed to

progress, gingivitis can turn into periodontitis, the invasion and destruction of the

underlying bone that anchors the teeth in place. As that happens, the gums may

recede, exposing the root surfaces and increasing sensitivity to heat and cold. Teeth

may even loosen because of bone destruction.

53

These conditions can arise for a variety of reasons. A severe deficiency of

vitamin C can lead to scurvy and result in bleeding, spongy gums, and eventual tooth

loss. And at least one periodontal disease - the uncommon but highly destructive

juvenile periodontitis - is thought to have a strong genetic basis. But as the terms

periodontal disease, gingivitis, and periodontitis are most commonly used, they refer

to disease that is caused by the build up of dental plaque.

Periodontitis begins with plaque. This invisible, sticky film forms on your

teeth when starches and sugars in food interact with bacteria normally found in your

mouth. Although you remove plaque every time you brush your teeth, it re-forms

quickly, usually within 24 hours.

Plaque that stays on your teeth longer than two or three days can harden under

your gumline into tartar (calculus), a white substance that makes plaque more

difficult to remove and that acts as a reservoir for bacteria. Unfortunately, brushing

and flossing can't eliminate tartar — only a professional cleaning can remove it.

The longer plaque and tartar remain on your teeth, the more damage they can

do. Initially, they may simply irritate and inflame the gingiva, the part of your gum

around the base of your teeth. This is gingivitis, the mildest form of periodontal

disease. But ongoing inflammation eventually causes pockets to develop between

your gums and teeth that fill with plaque, tartar and bacteria. In time, the pockets

become deeper and more bacteria accumulate, eventually advancing under your gum

tissue. These deep infections cause a loss of tissue and bone. If too much bone is

destroyed, you may lose one or more teeth.

The warning signs of gum disease include :

54

bleeding gums during tooth brushing

red, swollen or tender gums

gums that have pulled away from the teeth

persistent bad breath

pus between the teeth and gums

loose or separating teeth

a change in the way your teeth fit together when you bite

a change in the fit of partial dentures

2.11.1 Abscess

A dental abscess or sore is a bacterial infection that develops in the

mouth. While most dental abscesses develop in the gums, they can also

develop in the jaw bones, facial tissue, and throat. The vast majority of dental

infections are caused by poor dental hygiene. No matter how you look at it,

when teeth are not cleaned and taken care of properly, it leaves room for

bacteria to proliferate in various parts of the mouth.

Dental sores are usually caused by an infection that gets started within

a tooth. For example, if you have a cracked or chipped tooth, food particles

can get into the tooth and act as a hosting ground for bacteria. Some infections

also develop when pulp is left behind during a root canal.

If a tract develops, pus may start to drain from it. Some people also

notice that their teeth become more sensitive to hot and cold foods as the

infection evolves. Most people notice a swelling in the gum at the site of the

infection, pain and irritation as the abscess becomes larger.

Wound abscesses do not generally need to be treated with antibiotics,

but they will require surgical intervention, debridement and curettage.

2.11.2 PulpThe dental pulp is the soft tissue of the tooth, which develops from the

connective tissue of the dental papilla. Within the crown, the chamber

containing the dental pulp is called the pulp chamber. The pulp contains blood

55

vessels and nerves that enter through the apical foramen. The coronal pulp is

within the crown. Within the root is the radicular pulp.

2.11.3 GingivaGingiva is tough connective tissue which lines the base of the teeth,

holding them in place and protecting the jaw and teeth roots from infections.

Known informally as the gums, the gingiva are a very important part of the

oral anatomy, and caring for them is critical to maintaining oral health.

This connective tissue has a strong fibrous underlayer, covered in a

layer of mucous membranes. The gingiva are very tough, designed to resist

trauma from chewing and hard foods which enter the mouth. The base of this

tissue is firmly anchored to the bone, while the upper portion is free, allowing

the gingiva to run between the teeth to help stabilize them and keep them in

place. In addition to anchoring the teeth, the gingiva also create a seal which

prevents bacteria, plaque, and other foreign material from entering the roots of

the teeth, where it could cause trauma or infection.

When a patient's gingiva become chronically inflamed, the condition is

known as gingivitis. Classic symptoms of gingivitis can include changes in

the color of the gingiva, along with swelling and bleeding. Patients may find

that their gums are very tender after brushing their teeth, or that the gums

bleed freely after oral care or eating. Gingivitis can lead to complications

56

which include serious infections, and it is an issue which needs to be

addressed.

Over time, the gingiva can recede. Sometimes gum recession is caused

by gingivitis, but it can also be associated with other oral problems, or occur

on its own. Receding gums are a cause for concern because they can expose a

patient to the risk of infections and destabilize the teeth. Other gingival

diseases can include gingival cancer, in which the cells in the gums become

malignant, and gingival hyperplasia, in which the gums grow grossly

enlarged.

57

58

CHAPTER 4

DISCUSSION

4.1 Local factor and systemic factor of mobile tooth

Sometimes when there are mobile teeth, then it’s extracted, some people are

reluctant to make dentures, because they consider the manufacture of false teeth to fill

the room used the revocation is not important. but without tooth replacement, how to

chew will be changed. Slowly teeth will adapt to form a new composition. It is

common case is the shift of adjacent tooth and antagonist teeth towards the empty

room that revocation. In addition, the incomplete teeth in a jaw is usually not used to

chew, the result will occur caries that cause periodontitis.

4.2 Local factor

4.2.1 Periodontitis

Periodontal tissues can change because of environment influence. Principle,

It can be dissolves in water. Therefore, its existence in the mouth is according from

environment balance. Usually, there is a stability between environment and tooth,

salivary and plaque so that there is no mineral disappear from tooth tissues. The

stability of enamel is affected by pH and salivary composition.

Every day, one liter of salivary flow in the mouth. Enamel at long time will be

dissolved by salivary against is not solid with calcium and phosphate. Enamel is

consist of mineral like Ca10(PO4)6-(OH)2, hidroksipatit and others.

Human eat food that contain carbohydrate. There is two kinds of carbohydrate, that

is polysaccharide, monosaccharide, and disaccharide. Polysaccharide will be changed

59

to monosaccharide and disaccharide. Monosaccharide and disaccharide will be

ferment by dental plaque and the effect is the condition of the mouth will be in acid.

Actually Dental plaque formation starts almost immediately after tooth

brushing. Some minutes after brushing your teeth, saliva derived glycoprotein

deposits start to cover the tooth surface with what is referred to as "pellicle". The

formation of pellicle is the first step in dental plaque formation.

The pellicle is then colonized by Gram-positive bacteria such as

Streptococcus sanguis, Streptococcus mutants, and Actinomyces viscosus becoming

what is known as dental plaque. Bacteria cells interact with pellicle components

enabling plaque to firmly adhere to the tooth surface.

After 1 to 3 days following the initiation of plaque formation: the first

bacteria colonies start to multiply and expand and new bacteria species start to

colonize the tooth plaque. These new species include also Gram-negative bacteria

such as Fusobacterium nucleatum, Prevotella intermedia, and Capnocytophaga.

Substances produced by the already accumulated bacteria enrich the plaque

environment making it favourable for the growth of other species of bacteria. One

week after the first plaque accumulation, new Gram-negative species may be found,

such as Porphyromonas gingivalis, Campylobacter rectus, Eikenella corrodens,

Actinobacillus actinomycetemcomitans, and oral spirochetes (Treponema species).

While the dental plaque formation continues Gram-negative species become

dominant over the Gram-positive species. The overgrowth of Gram-negative

anaerobic bacteria is considered as pathogenic plaque

As the result of acid formation by bacteria in plaque, PH become 5,5 at the

limit surface of enamel and plaque. The result of decreasing is enamel under plaque

become demineralization because builder material of enamel dissolve, also because

buffer capacity of salivary is not fulfill.

60

At early phase, new white spot is seen as clinical after dried by air sprayer,

because liquid in small pore, keep enamel translucent character. Because the way of

drainage, liquid will be disappear and also enamel translucent character. At the

middle phase, white spot can be seen without help. The shape of white spot is fit with

the shape of plaque. So in the part that is not clean, will be develop white spot.

During a day, there will be acid release. Every time plaque is supplied by

sugar, PH will be decrease under crisis value 5,5 and at last PH become neutral.

Along with increasing PH, there will be formed sediment of calcium and phosphate

from enamel. The sediment is called Calculus. Furthermore, because calcium and

phosphate is dissolved from enamel, then pore in enamel will be expanding. This is

called caries.

A. Calculus

Calculus is classified by location into supra-gingival and sub-gingival

calculus. Often, both types occur together. Supra-gingival calculus is adherent to the

teeth and Subgingival calculus forms on root surfaces below the gingival margin and

can extend deep into periodontal pockets. A more irregular subgingival cemental

surface allows deposits to form into the cemental irregularities. This makes the

attachment of the subgingiva calculus more tenacious and difficult to remove. It also

tends to be darker or black in color. All calculus can however absorb extrinsic stains

(coffee; tea; tobacco;etc) and appear dark brown or black.

Calculus usually found in proximal part of the teeth. More acid release

happened in the mouth, more calculus cumulation on sideline of teeth. Calculus

cumulation causes gingival open widely, and calculus will enter around ligament

tissues. Because more calculus enter and cling into ligament tissues, ligament tissues

will be damaged. Gingival will be drop off. The effect is there is no prop tissues and

the tooth become loose.

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B. Caries

Enamel is a highly mineralized acellular tissue, and caries act upon it through

a chemical process brought on by the acidic environment produced by bacteria. As

the bacteria consume the sugar and use it for their own energy, they produce lactic

acid. The effects of this process include the demineralization of crystals in the

enamel, caused by acids, over time until the bacteria physically penetrate the dentin.

In dentin from the deepest layer to the enamel, the distinct areas affected by

caries are the translucent zone, the zone of destruction, and the zone of bacterial

penetration. The translucent zone represents the advancing front of the carious

process and is where the initial demineralization begins. The zones of bacterial

penetration and destruction are the locations of invading bacteria and ultimately the

decomposition of dentin.

If caries is not treated, caries will spread until the pulp. In the pulp, there is

tooth nerve and blood tube. Pulp will be infected. Abscess or fistula (the road from

the pus) can form in soft connective tissue. Abscess causes gingival diseases named

periodontitis.

Periodontitis is an inflammation of the gingival unit (gingival and alveolar

mucosa) and extends to the periodontal ligament, alveolar bone, and cementum.

Periodontitis involves loss of bone.

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Periodontitis causes inflammantion in gingival and make ligament periodontal

tissues apart from alveolar bone. This divorce make a small space known as

periodontal pocket. Bacterial toxins and the body's enzymes fighting the infection

start to break down the bone and connective tissue that hold teeth in place. As the

periodontal disease progresses, the pockets deepen and more gingival tissue and

alveolar bone are destroyed. Ultimately all the supporting structures of the tooth may

be lost. The tooth gradually loosens and, if periodontitis is left untreated, the tooth

will eventually be lost. Periodontitis can be the conversion of gingivitis.

Gingivitis is an inflammatory process affecting the soft tissues

surrounding the teeth. But the inflammatory does’t extend into the alveolar bone,

periodontal ligament, or cementum like periodontitis does. The primary factor of

gingivitis is bacterial plaque.

4.3 Systemic factor

4.3.1 Diabetes Mellitus

Diabetes mellitus is a metabolic disorder with characteristic hyperglycemia,

because disruption of insulin production from pancreatic beta cells, insulin

dysfunction or disruption of insulin receptor on the target organ. In a state of

uncontrolled hyperglycemia is characterized by polyuria, polydipsia, polyphagia.

Diabetes mellitus as known as diabetes is a disease caused by lack of insulin

in the body resulting in ganngguan Primary glucose metabolism disorder

characterized by increased levels of glucose in the blood exceeds the normal value.

In diabetes mellitus can occur a number of complications caused by high

blood glucose levels (hyperglycemia). Some protein bodies in diabetes mellitus with

hyperglycemia will have glycosylation, with the consequent increase in the amount of

glycated IgG. The glycosylation state of hyperglycemia and experience will reduce

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the affinity of IgG antibodies against the antigen, so that people with diabetes

mellitus susceptible to infection. It was reported that there is a correlation between

blood glucose levels with the prevalence of severity of gingival inflammation,

periodontal, and alveolar bone resorbsi kedlaman pocket. Gigngiva tissue resistance

and diabetes mellitus peridontal tissue decreased, due to a change in the composition

of collagen, the regulation of diabetes mellitus and oral hygiene.

In diabetes mellitus frequent disruption of immune defenses that resulted in

the nature of leukocyte decreased phagocytosis, decreased antibody formation so that

the immune will be decreased. If chronic complications occurred in patients with

diabetes mellitus will occur quality of blood vessels disorder known as Angiopathy

diabetic. The elasticity of blood vessel walls disappear and thickening of

proliferation, hyalinization causes the blood vessels become stiff and easily broken,

there arose a leak. The leak resulted in the release of proteins and grains - grains that

result in decreased blood of the local network defense since the release of grain -

grain blood such as leukocyte and decreasing supply of nutrients and oxygen to the

tissues that hamper healing. Diabetic neuropathy factors caused a decline in

autonomic reflexes and no ability to vasoconstriction of blood vessels and capillary.

No. Criteria of DM Diagnostic

1.

Classic symptoms : polyuria, polydipsia, polyphagia, weight

loss, increased blood glucose levels for a while ≥ 200mg/dl

(11,1 mmol/l)

2. Blood glucose levels when fasting ≥ 126 mg/dl (7,0 mmol/l)

3.Blood glucose levels ≥ 200 mg/dl (11,1 mmol/l) 2 hours

after 75 gram glucose load

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4.4 Mechanism of periodontitis in diabetes mellitus

Diabetics have an oral bacterial flora similar to that found in nondiabetics, but

their response to infection is not same. Diabetics have been shown to have markers of

systemic inflammation, and it has been postulated that this inflammatory state can

lead to increased destruction of the chronically infected periodontium. These markers

include elevated C-reactive protein, fibrinogen and decreased albumin. Not only do

diabetics have increased levels of systemic pro-inflammatory mediators, the local

environment of the periodontium is also affected by higher levels of inflammation.

An example of local inflammation occurs when monocytes increase production of

inflammatory cytokines in response to insult; this increase in inflammatory mediators

remains even after removal of the offending stimulus. Diabetics, therefore, have

increased systemic and local inflammation, which contributes to increased destruction

of the periodontium.

Furthermore, diabetics have an altered response to wound healing and an

abnormal immune response. Fibroblast function is impaired because of the high

levels of glucose, and collagen availability is decreased by higher levels of the

proteins that degrade collagen, that is, matrix metalloproteinases. The decreased

fibroblast function and collagen availability alter the healing response in diabetics.

The immune response, which is considered a characteristic trait of diabetes, includes

abnormal chemotaxis; adherence and phagocytosis of neutrophils. This provides an

altered environment in which oral bacteria can thrive; therefore, systemic and local

inflammation, altered wound healing and an abnormal immune response contribute to

destruction of the periodontium in diabetic individuals.

Disruption of insulin secretion or insulin resistance causes disruption of the

insulin receptor resulting in hyperglycemia. hyperglycemia causes fat and protein

glycosylation will experience in non-systematic, forming Schiff bases, which then

form amadori products. amadori degradation products generate reactive carbonyl

65

compounds that react with free amino group which then form the AGE that is

irreversible, unstable, reactive, and can cause vascular dysfunction.

AGE is a toxic compound that can trigger mutagenesis of bacteria. AGE was

formed over the case of DM. The main chemical compounds found in AGEs in the

human body are pentosidine and carboxy methyl lysine. AGEs will be captured by

the AGE receptor (RAGEs) in endothelial and will form a reactive free radical

compounds.

Accumulation of AGEs affect cell migration and phagocytosis activity

polimorphonuclear (PMN) and macrophages against microbes / pathogens.

Maturation and gradual changes in subgingival microflora and when accompanied by

a pocket depth of ulcer showed the changes of chronic systemic disease, characterized

by secretion of IL-1ß and TNF-α, insulin resistance that affect glucose metabolism.

Interaction between macrophage phagocyte cells with AGEs induced expression of

cytokines and induce oxidative stress. Simultaneously, periodontal infection can

induce persistent insulin resistance, followed by hyperglycemia, glikolosasi

nonsimatik the irreversible, accumulation of AGE-binding proteins, which then

accompanied by destruction and degradation of connective tissue proliferation.

Molecular mechanisms of periodontitis in patients with diabetes mellitus is

based on changes in host response and collagen metabolism. The main factors that

affect host response to the development of complications of diabetes mellitus is a

long exposure to hyperglycemia network that will generate AGEs. AGEs bind to

receptors AGEs (RAGEs) on endothelial cells, monocytes, macrophages and

fibroblasts. Furthermore, AGEs change the collagen tissue to increase a formation of

crosslinking and the formation of reactive oxygen intermediates (ROI) such as the

formation of free radicals. Fibers of collagen that has changed accumulate in the

tissues and being thick in basalis membrane. And will occur the oxygen diffusion

disorder, leukocyte migration, immune factor diffusion that will cause periodontitis

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In addition, hyperglicemia will increase the collagenase synthesis. The increse

of collagenase activity in Diabetes Mellitus patient occur the defect of collagen tissue,

then will break the periodontal tissue component in diabetic patient.

The common oral manifestations of diabetes include the following: gingivitis;

periodontal disease; multiple periodontal abscesses, xerostomia and salivary gland

dysfunction; recurring bacterial, viral and fungal (Candida) infections; dental caries;

periapical abscesses; loss of teeth; delayed wound healing; burning mouth syndrome;

taste impairment; and oral lichen planus.

4.5 Solutions to minimize the oral effect of Diabetes Mellitus

When it is discovered that a patient with advanced dental disease also has

diabetes, extractions should not be performed, unless absolutely necessary, until the

systemic condition is brought under control. Acute abscesses, however, require

immediate drainage. Admittedly, complete regulation may not be possible while

dental infection is still present, but the glycemia can be reduce. With the amelioration

of the diabetic status there may be dramatic improvement in the acute periodontal

condition. The teeth may become firmer, gingival inflammation may subside,

suppurative exudates from the gingival crevices may decrease, and soreness and

sensitivity may lessen. At this stage dental evaluation may be carried out and

necessary treatment instituted. Teeth in a hopeless condition may now be extracted

and residual fluctuating, uncontrollable sugar levels to a more manageable state.

Thus, the treatment of periodontal disease may facilitate the practical regulation of

diabetes.

Under good medical control and with enlightened dental care, the diabetic

patient shows no greater tendency to postdental surgical complications than his

nondiabetic counterpart. Dental treatment is in most instances a stressful event, and,

67

therefore, certain precautions in the handling of the diabetic dental patient are

judicious and advisable. Dental appointment should be in the morning, generally

about an hour and a half after breakfast and the administration of the morning insulin.

Those patients receiving intermediate and long-acting insulin in the morning before

breakfast may be treated safely in the early afternoon also. Every effort should be

made to allay apprehension and minimize pain. The rational administration of

sedatives and analgesics preoperatively

The steps of treatment for diabetic patient :

1. Control the glycemia regularly (min. every 3 month) because the good

condition of glycemia will be improve periodontal disease

2. Check your gingival or periodontal, then clean the plaque and calculus every

3-6 month

Treatment of plaque and calculus

A. Scaling : Scaling is a type of cleaning that removes plaque and

calculus from the teeth at and slightly below the gumline.

B. Root Planing : Root planing smoothes root surfaces, so the

supportive tissues can better reattach to the tooth surface

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C. Periodontal Debridement: This includes the removal of plaque, and

calculus both above and below the gingival

D. Prophy / Prophylaxis: A preventive procedure to remove local

irritants to the gingiva, including debridements of calculus and

removal of plaque.

E. Scaling and root planing can be done utilizing a non-surgical (closed)

approach or a surgical (open) approach

A non surgical approach is when access to the root surfaces is via

the sulci or periodontal pockets. Periodontal disease is a bacterial

disease and the key to controlling or eliminating it is the effective

reduction or elimination of the harmful bacteria. An adjunctive

option to scaling and root planing may be provided in either pill

form or applied directly to the infected area (gum pocket) in the

form of antibiotic powder. An antibacterial mouth rinse also may be

prescribed to help control the harmful effects of and reduce

bacterial plaque.

A surgical approach is when full thickness tissue flaps are reflected

to expose the root surfaces and gain direct access to them

The efficacy of subgingival plaque and calculus removal utilizing a

non surgical approach is limited. Pockets up to 5mm may be

69

adequately debrided using a closed approach, but deeper pockets

often will require an open or sugical approach.

3. Use good toothbrush. brush your teeth in the right way twice a day

4. Substitute the missing tooth

Sometimes we meet diabetic patient that loss his tooth by itself. So we need

removable dentures for substitute it. Why we do not use permanent false tooth

such as ‘bridge’? Because it makes another teeth also mobiling

How about dental implant? Diabetic patient has serious problem with his

periodontal. Gingival is easy to inflame, then become abscesses. Implant only

makes it worse

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So removable dentures is the best way to substitute the missing tooth. It do

not makes another teeth mobiling, and also safe for the diabetic patient’s

periodontal

PERIODONTIA

Diabetes Mellitus (DM) is a predisposing factor to onset of infection. In the mouth,

DM can increase the number of bacteria that cause abnormalities in the periodontal

tissues and if it continues to cause tooth becomes wobbly.

In Diabetic patient, the risk of getting infected with periodontal tissue even 2-4 times

greater than non-diabetic patients. Chronic periodontal infection causes systemic

inflammation which will increase insulin resistance and hyperglycemia.

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Insulin resistance inhibits optimal glycemic control and increase the risk of heart

disease. Diabetes may be the main cause gingival lesions, xerostomia, hiperaemi

mucosa, palate and tongue felt dry/ burning, loss of tongue papilla and vascular

problems early.

a. It is suggested that the lower the degree of shakiness teeth in patients with

diabetes mellitus, should regularly control the blood glucose level of at least

three months

b. For patients wit IDDM, by inhibiting the inflammatory response against

gram-negative bacterial infections such as those found in periodontal disease.

c. Recommends brushing with a toothpaste contain triclosan/ copolymer of at

least two times a day and HbA1c test at least three monts.

ORAL SURGERY

Tooth extraction in patients with disorders of systemic disease requires serious

consideration of some aspects of action and reaction. Patients with diabetes mellitus

have a higher risk of tooth extraction. Blood clots in people with diabetes mellitus,

either IDDM or NIIDM slightly disturbed. It means the patient’s cloting time does

not like the non-diabetic. One of the acute complications of diabetes mellitus is non

ketotik hiperosmoler coma.

This disease is due to high blood sugar levels exceed 600 mg which resulted in easy

shock patients.

a. After paraesthesia, extraction should be followed by a tampon for 30 minutes.

This is done so that bleeding can be resolved.

b. The addition of insulin to prevent shock

At surgery, there is little difference between patients with DM type 1 and type 2. In

people with type 1 diabetes, before surgery should be performed insulin therapy, by

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giving injections of insulin therapy, by giving injections of insulin because of insulin

are not sufficient. While in type 2 diabetes, need not be given an injection of insulin.

In addition, the provision of local anesthesia, patients with DM should be avoided

from vasoconstrictor substances because they contain adrenaline that can increase

glucose in the blood.

PROSTHODONTIA

Systemic diseases such as diabetes mellitus can inhibit prostodontia maintance.

Serious chronic illness and reduce physiological adaptable. In patients with diabetes

mellitus, patients usually reluctant to return to control because no confidence against

the typical bad breath. This can inhibit the development of growth occurring

observation. In addition, xerostomia is a symptom of diabetes mellitus can also

inhibit Orthodontic retention by inhibiting the adhesion between the base of

removable dentures with oral mucosa with oral mucosa and salivary fluid power

cohesion.

a. Need to avoid major changes in the conditions of the oral cavity or artificial

tooth shape drastically.

b. Avoided printed materials using because these materials adsorbs plaster moist

oral cavity.

ORTHODONTIA

Patients with DM on orthodonsia treatment, for example in the use of orthodontia

device (wire) can causes gingivitis. In DM patients there is a tendency mobile tooth.

This is one of the contra-indication teeth spread, because with the use of wire, will

generate too much pressure on the teeth, so teeth become mobile that will untimately

lead to tooth loss.

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CHAPTER 5

SUMMARY

5.1 Conclusion

The cause of mobile tooth divided into two factors, local factor and systemic

factor. First, local factor caused by streptococcus mutans which is appear plaque

around our tooth and make our mouth become very acid. At last, in our tooth occur

periodentitis and periodental abses which is make mobile tooth. Second, systemic

factor caused by diabetes mellitus. If blood glucose level isn’t controlled influence

mobile tooth. So from our disccusion, we conclude that people’s opinion is wrong.

5.2 Suggestion

To avoid the factors of mobile tooth we should :

1. Increase oral hygine with tooth brushing frequently (Use good toothbrush.

brush your teeth in the right way twice a day )

2. Every 6 month, we must control our tooth condition in dentist

3. Control the glycemia regularly (min. every 3 month) because the good

condition of glycemia will be improve periodontal disease

4. Check your gingival or periodontal, then clean the plaque and calculus every

3-6 month .

5. Use false tooth for diabetes’s suffer ( not allow use implant )

74

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