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 aldohexose. 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 -CH 2OH
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.

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

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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.

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

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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
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.

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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
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.

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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.
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

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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
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,

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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-
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

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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.

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,

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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
(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

15
 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. 

 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.

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 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
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

17
 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
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.

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 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.

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

19
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.
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

20
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. 

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

21
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.

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.

22
 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
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

23
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
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

24
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
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

25
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
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

26
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
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

27
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
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.

28
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

180 mg/dl = 10 mmol/l

270 mg/dl = 15 mmol/l

288 mg/dl = 16 mmol/l

360 mg/dl = 20 mmol/l

29
 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.

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

30
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

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.

31
 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.

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

32
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.

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.

33
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).
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.

34
 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
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

35
 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.
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

36
 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
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

37
 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
transplant, in which (undifferentiated) hematopoietic stem cells are
transferred.

2.6.2. Active immunity

38
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
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

39
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
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.

40
 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
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

41
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
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

42
 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
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

43
 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)
 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,

44
 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
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,

45
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]

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

46
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
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

47
 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.
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

48
 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
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

49
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
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.

50
 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 (NO 3- >
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 NO 3-.
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 NO 2- is chemically reduced to
NO in acidic microenvironments in the oral cavity. The underlying processes have
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

51
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
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

52
 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.

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

53
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 :
 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

54
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 Pulp
The 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
vessels and nerves that enter through the apical foramen. The coronal pulp is
within the crown. Within the root is the radicular pulp.

55
2.11.3 Gingiva
Gingiva 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
which include serious infections, and it is an issue which needs to be
addressed.

56
 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
CHAPTER 4

DISCUSSION

58
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
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.

59
 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.

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

60
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.

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

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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.

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

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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
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

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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

Classic symptoms : polyuria, polydipsia, polyphagia, weight loss,
1.
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)
Blood glucose levels ≥ 200 mg/dl (11,1 mmol/l) 2 hours after 75 gram
3.
glucose load

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

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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
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.

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 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

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.

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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,
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

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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

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.

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 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
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

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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.

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

71
 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
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

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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.

CHAPTER 5

SUMMARY

5.1 Conclusion

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 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 )

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