Diabetes mellitus encompasses a spectrum of disease that affects the way in which your body uses glucose (sugar). Glucose is essential to good health; it's a vital source of energy for the body's cells. The brain also uses glucose as the main source of energy. A person's well-being depends on some degree on the efficient use of glucose within the body. Diabetes can cause a wide range of symptoms, including excess sweating, weight loss, and slow healing wounds.
The reasons why someone develops diabetes varies, depending on the type. However, all types of diabetes will result in excessive amounts of glucose in the blood. Excess blood sugar can lead to very serious health issues. Diabetes and sweating is one relatively minor symptom, while permanent blindness is one of the most serious effects of uncontrolled diabetes.
Chronic diabetes manifests as type 1 diabetes and type 2 diabetes. There are also two potentially reversible forms of diabetes. The first is prediabetes; this is when the blood sugar level is higher than normal but not yet high enough to be diagnosed as diabetes. The second type of potentially reversible diabetes is gestational diabetes; this happens during pregnancy but clears up after the birth of the baby.
DIABETES SYMPTOMS
The seriousness of the symptoms can depend on how high or low blood sugar levels are. Some who have diabetes may not detect any symptoms at first, especially if they have prediabetes or type 2 diabetes. However, those with type 1 diabetes tend to have more severe symptoms that manifest more quickly.
SOME TYPE 1 AND TYPE 2 DIABETES SYMPTOMS ARE:
Excessive sweating
Frequent urination and thirst
Extreme hunger and fatigue
Unexplained weight loss
Ketones in the urine
Irritability
Blurred vision
Slow-healing wounds
Although type 1 diabetes can develop at any age, it most often is diagnosed during childhood or adolescence. Type 2 diabetes can also develop at any age, but it's more commonly diagnosed in those over 40 years of age.
DIABETES AND SWEATING
Low blood sugar levels is a part of the diabetic cycle; it's called hypoglycemia. Hypoglycemia will trigger the body into a fight-or-flight response. This, in turn, causes the body to produce more adrenaline and norepinephrine which can cause heavy sweating, as well as diabetes symptoms of anxiety and shakiness.
EXTREME HUNGER AND FATIGUE
The body converts food into glucose so that the body can use that sugar for energy. However, the body's cells require insulin to utilize glucose. If the body doesn't make enough insulin, or if the cells are insulin resistant, the glucose can't fuel the cells, resulting in hunger and fatigue.
FREQUENT URINATION AND EXCESSIVE THIRST
The average person urinates from four to seven times a day. However, those with diabetes may need to urinate a lot more. Normally, the body will reabsorb glucose when it passes through the kidneys. But as diabetes increases the blood sugar, the kidneys may not be able to reabsorb all of it. This triggers the body to produce more urine. More urine requires more fluids, thus, the diabetic becomes thirsty.
UNEXPLAINED WEIGHT LOSS
Insufficient insulin will stop the body from absorbing blood glucose into the body's cells for energy. When this happens, the body will burn muscle and fat for energy. This results in weight loss. Unusual weight loss often occurs prior to a diagnosis of type 1 diabetes. However, unexpected weight loss can also affect those with type 2 diabetes.
KETONES IN THE URINE
If the body's cells receive inadequate amounts of glucose, the body will begin to burn fat for energy. This will produce ketones, which will show up in the urine. High levels of ketones in the urine can indicate diabetic ketoacidosis. This diabetic symptom can lead to a coma or in extreme cases, death.
IRRITABILITY
Low glucose levels may cause a range of emotional symptoms including irritability, moodiness, and belligerence. If a diabetic experiences irritability it's advisable to check their blood sugar levels.
BLURRED VISION
High blood sugar levels can affect your vision; it causes the lens of the eye to swell, which results in temporary blurry eyesight. However, blurry vision can also be the result of low blood sugar. In the case of low blood sugar, vision should return to normal once the blood glucose is back to a normal range. However, if diabetes is not controlled, it can cause irreversible damage to the eyes, resulting in permanent blindness.
SLOW-HEALING WOUNDS
When blood sugar levels are higher than normal, it will prevent oxygen and nutrients from feeding the cells. This will, in turn, stop the immune system from functioning properly. Abnormal blood sugar levels can also increase inflammation, which will affect healing. In extreme cases of uncontrolled diabetic infections, amputations of the feet are not uncommon.
FREQUENT INFECTIONS
High blood sugar can make a diabetic prone to infections. One reason is that yeast feeds on sugar; as a result of the combination of high blood sugar, and lowered immunity, yeast infections can easily get out of control in someone with diabetes.
DIABETIC NEUROPATHY
Neuropathy is a type of nerve damage. High blood sugar can cause damage to the nerves throughout the body. However, diabetic neuropathy most often targets the nerves in the lower legs and feet. Symptoms of diabetic neuropathy can vary from numbness or pain and in the legs and feet to trouble with the urinary tract, the digestive system, the blood vessels, and even the heart. Some diabetics have mild neuropathy symptoms, but other diabetics can experience debilitating pain.
FOUR TIPS FOR MANAGING DIABETES
Effectively controlling diabetes takes daily effort, but the benefits are well worth it. The payoff will be a longer and healthier life.
CHECK YOUR BLOOD SUGAR
Follow your doctor's schedule for checking your blood sugar, and add extra checks periodically. If you feel irritable or begin sweating, do a blood sugar check. Diabetes and sweating is a sign of low blood sugar.
KEEP TRACK OF YOUR CARBS
Carbohydrates convert quickly into sugar once digested. Limit your intake of high carb foods like bread, pasta, potatoes, and chips.
GET REGULAR EXERCISE
Exercise will burn off excess glucose in the blood. Try to get at least 2-3 hours of exercise per week, in daily increments.
KNOW ALL OF YOUR NUMBERS
Blood sugar levels are not the only numbers you need to know. You also need to watch your cholesterol and blood pressure readings.
To sum things up, diabetes can have very serious health complications, but it can be managed. Pay attention to your symptoms, and take the steps necessary to manage your diabetes, not only with medication but with common sense diet and exercise routines. If you like this article, please share!
In diabetes mellitus, your body has trouble moving glucose, which is a type of sugar,
from your blood into your cells.
This leads to high levels of glucose in your blood and not enough of it in your cells,
and remember that your cells need glucose as a source of energy, so not letting the
glucose enter means that the cells starve for energy despite having glucose right on
their doorstep.
In general, the body controls how much glucose is in the blood relative to how much gets
into the cells with two hormones: insulin and glucagon.
Insulin is used to reduce blood glucose levels, and glucagon is used to increase blood glucose
levels.
Both of these hormones are produced by clusters of cells in the pancreas called islets of
Langerhans.
Insulin is secreted by beta cells in the center of the islets, and glucagon is secreted by
alpha cells in the periphery of the islets.
Insulin reduces the amount of glucose in the blood by binding to insulin receptors embedded
in the cell membrane of various insulin-responsive tissues like muscle cells and adipose tissue.
When activated, the insulin receptors cause vesicles containing glucose transporter that
are inside the cell to fuse with the cell membrane, allowing glucose to be transported
into the cell.
Glucagon does exactly the opposite, it raises the blood glucose levels by getting the liver
to generate new molecules of glucose from other molecules and also break down glycogen
into glucose so that it can all get dumped into the blood.
Diabetes mellitus is diagnosed when the blood glucose levels get too high, and this is seen
among 10% of the world population.
There are two types of diabetes - Type 1 and Type 2, and the main difference between them
is the underlying mechanism that causes the blood glucose levels to rise.
About 10% of people with diabetes have Type 1, and the remaining 90% of people with diabetes
have Type 2.
Let’s start with Type 1 diabetes mellitus, sometimes just called type 1 diabetes.
In this situation, the body doesn’t make enough insulin.
The reason this happens is that in type 1 diabetes there is a type 4 hypersensitivity
response or a cell-mediated immune response where a person’s own T cells attack the
pancreas.
As a quick review, remember that the immune system has T cells that react to all sorts
of antigens, which are usually small peptides, polysaccharides, or lipids, and that some
of these antigens are part of our own body’s cells.
It doesn’t make sense to allow T cells that will attack our own cells to hang around,
and so there’s this process to eliminate them called “self-tolerance”.
In type 1 diabetes, there is a genetic abnormality causes a loss of self-tolerance among T cells
that specifically target the beta cell antigens.
Losing self-tolerance means that these T cells are allowed to recruit other immune cells
and coordinate an attack on these beta cells.
Losing beta cells means less insulin, and less insulin means that glucose piles up in
the blood, because it can’t enter the body’s cells.
One really important genes involved in regulation of the immune response is the human leukocyte
antigen system, or HLA system.
Although it’s called a system, it’s basically this group of genes on chromosome six that
encode the major histocompatibility complex, or MHC, which is a protein that’s extremely
important in helping the immune system recognize foreign molecules, as well as maintaining
self-tolerance.
MHC is like the serving platter that antigens are presented to the immune cells.
Interestingly, people with type 1 diabetes often have specific HLA genes in common with
each other, one called HLA-DR3 and another called HLA-DR4.
But this is just a genetic clue right?
Because not everyone with HLA-DR3 and HLA-DR4 develops diabetes.
In diabetes mellitus type 1, destruction of beta cells usually starts early in life, but
sometimes up to 90% of the beta cells are destroyed before symptoms crop up.
Four clinical symptoms of uncontrolled diabetes, that all sound similar, are polyphagia, glycosuria,
polyuria, and polydipsia.
Let’s go through them one by one.
Even though there’s a lot of glucose in the blood, it can’t get into cells, which
leaves cells starved for energy, so in response, adipose tissue starts breaking down fat, called
lipolysis, and muscle tissue starts breaking down proteins, both of which results in weight
loss for someone with uncontrolled diabetes.
This catabolic state leaves people feeling hungry, also known as polyphagia.
“Phagia” means eating, and “Poly” means a lot.
Now with high glucose levels, that means that when blood gets filtered through the kidneys,
some of it starts to spill into the urine, called glycosuria.
“Glycos” refers to glucose, “uria” the urine.
Since glucose is osmotically active, water tends to follow it, resulting in an increase
in urination, or polyuria.
“Poly” again refers to a lot, and “uria” again refers to urine again.
Finally, because there is so much urination, people with uncontrolled diabetes become dehydrated
and thirsty, or polydipsia.
“Poly” means a lot, and “dipsia” means thirst.
Even though people with diabetes aren’t able to produce their own insulin, they can
still respond to insulin, so treatment involves lifelong insulin therapy to regulate their
blood glucose levels and basically enable their cells to use glucose.
One really serious complication with type 1 diabetes is called diabetic ketoacidosis,
or DKA.
To understand it, let’s go back to the process of lipolysis, where fat is broken down into
free fatty acids.
After that happens, the liver turns the fatty acids into ketone bodies, like acetoacetic
acid and beta hydroxybutyric acid, acetoacetic acid is a ketoacid because it has a ketone
group and a carboxylic acid group.
Beta hydroxybutyric acid on the other hand, even though it’s still one of the ketone
bodies, isn’t technically a ketoacid since its ketone group has been reduced to a hydroxyl
group.
These ketone bodies are important because they can be used by cells for energy, but
they also increase the acidity of the blood, which is why it’s called keto-acid-osis.
If the blood becoming really acidic can have major effects throughout the body.
Patients can develop Kussmaul respiration, which is a deep and labored breathing as the
body tries to move carbon dioxide out of the blood, in an effort to reduce its acidity.
Cells also have a transporter that exchanges hydrogen ions (or protons—H+) for potassium.
When the blood gets acidic, it is by definition loaded with protons that get sent into cells
while potassium gets sent into the fluid outside cells.
Another thing to keep in mind is that in addition to helping glucose enter cells, insulin stimulates
the sodium-potassium ATPases which help potassium get into cells, and so without insulin, more
potassium stays in the fluid outside cells.
Both of these mechanisms lead to increased potassium in the fluid outside of cells which
quickly makes it into the blood and causes hyperkalemia.
The potassium is then excreted, so over time, even though the blood potassium levels remain
high, overall stores of potassium in the body—which includes potassium inside cells—starts to
run low.
Patients will also have a high anion gap, which reflects a large difference in the unmeasured
negative and positive ions in the serum, largely due to this build up of ketoacids.
Diabetic ketoacidosis can happen even in people who’ve already been diagnosed with diabetes
and currently have some sort of insulin therapy.
In states of stress, like an infection, the body releases epinephrine, which in turn stimulates
the release of glucagon.
Too much glucagon can tip the delicate hormonal balance of glucagon and insulin in favor of
elevating blood sugars and can lead to a cascade of events we just described—increased glucose
in the blood, loss of glucose in the urine, loss of water, dehydration, and in parallel
a need for alternative energy, generation of ketone bodies, and ketoacidosis.
Interestingly, both ketone bodies break down into acetone and escape as a gas by getting
breathed out the lungs which gives a sweet fruity smell to a person’s breath.
In general though, that’s the only sweet thing about this illness, which also causes
nausea, vomiting, and if severe, mental status changes and acute cerebral edema.
Treatment of a DKA episode involves giving plenty of fluids, which helps with dehydration,
insulin which helps lower blood glucose levels, and replacement of electrolytes, like potassium;
all of which help to reverse the acidosis.
Now, let’s switch gears and talk about Type 2 diabetes, which is where the body makes
insulin, but the tissues don’t respond as well to it.
The exact reason why cells don’t “respond” isn’t fully understood, essentially the
body’s providing the normal amount of insulin, but the cells don’t move their glucose transporters
to their membrane in response, which remember is needed for glucose to get into the cell,
these cells therefore they have insulin resistance.
Some risk factors for insulin resistance are obesity, lack of exercise, and hypertension,
and the exact mechanisms are still being explored.
For example, an excess of adipose tissue—or fat—is thought to cause the release of free
fatty acids and so-called “adipokines”, which are signaling molecules that can cause
inflammation, which seems related to insulin resistance.
However, many people that are obese are not diabetic, so genetic factors probably play
a major role as well.
We see this when we look at twin studies as well, where having a twin with type 2 diabetes
increases the risk of developing type 2 diabetes, completely independent of other environmental
risk factors.
In Type 2 diabetes, since tissues don’t respond as well to normal levels of insulin,
the body ends up producing more insulin in order to get the same effect and move glucose
out of the blood.
They do this through beta cell hyperplasia, an increased number of beta cells, and beta
cell hypertrophy, where they actually grow in size, all in this attempt to pump out more
insulin.
This works for a while, and by keeping insulin levels higher than normal, blood glucose levels
can be kept normal, called normoglycemia.
Now, along with insulin, beta cells also secrete islet amyloid polypeptide, or amylin, so while
beta cells are cranking out insulin they also secrete an increased amount of amylin.
Over time, amylin builds up and aggregates in the islets.
This beta cell compensation, though, isn’t sustainable, and over time those maxed out
beta cells get exhausted, and they become dysfunctional, and undergo hypotrophy and
get smaller, as well as hypoplasia and die off.
As beta cells are lost and insulin levels decrease, glucose levels in the blood start
to increase, and patients develop hyperglycemia, which leads to similar clinical signs that
I mentioned before, like polyphagia, glycosuria, polyuria, and polydipsia.
But unlike type 1 diabetes, there is generally some circulating insulin in type 2 diabetes
from the beta cells that are trying to compensate for the insulin resistance.
This means that the insulin/glucagon balance is such that diabetic ketoacidosis doesn’t
usually develop.
Having said that, a complication called hyperosmolar hyperglycemic state (or HHS) is much more
common in type 2 diabetes than type 1 diabetes - and it causes increased plasma osmolarity
due to extreme dehydration and concentration of the blood.
To help understand this, remember that glucose is a polar molecule that cannot passively
diffuse across cell membranes, which means that it acts as a solute.
So when levels of glucose are super high in the blood (meaning it’s a hyperosmolar state),
water begins to leave the body’s cells and enter the blood vessels, leaving the cells
relatively dry and shriveled rather than plump and juicy.
Blood vessels that are full of water lead to increased urination and total body dehydration.
And this is a very serious situation because the dehydration of the body’s cells and
in particular the brain can cause a number of symptoms including mental status changes.
In HHS, you can sometimes see mild ketonemia and acidosis, but not to the extent that it’s
seen in DKA, and in DKA you can see some hyperosmolarity, so there is definitely overlap between these
two syndromes.
Besides type 1 and type 2 diabetes, there are also a couple other subtypes of diabetes
mellitus.
Gestational diabetes is when pregnant women have increased blood glucose which is particularly
during the third trimester.
Although ultimately unknown, the cause is thought to be related to pregnancy hormones
that interfere with insulin’s action on insulin receptors.
Also, sometimes people can develop drug-induced diabetes, which is where medications have
side effects that tend to increase blood glucose levels.
The mechanism for both of these is thought to be related to insulin resistance (like
type 2 diabetes), rather than an autoimmune destruction process (like in type 1 diabetes).
Diagnosing type 1 or type 2 diabetes is done by getting a sense for how much glucose is
floating around in the blood and has specific standards that the World Health Organization
uses.
Very commonly, a fasting glucose test is taken where the person doesn’t eat or drink (except
water, that’s okay) for 8 hours and has their blood tested for glucose levels.
Levels of 100 110 milligrams per deciliter to 125 milligrams per deciliter indicates
prediabetes and 126 milligrams per deciliter or higher indicates diabetes.
A non-fasting or random glucose test can be done at any time, with 200 milligrams per
deciliter or higher being a red flag for diabetes.
Another test is called an oral glucose tolerance test, where a person is given glucose, and
then a blood samples are taken at time intervals to figure out how well it’s being cleared
from the blood, the most important interval being 2 hours later.
Levels of 140 milligrams per deciliter to 199 milligrams per deciliter indicate prediabetes
and 200 or above indicates diabetes.
Another thing to know is that when blood glucose levels get high, the glucose can also stick
to proteins that are floating around in the blood or in cells.
So that brings us to another type of test that can be done which is the HbA1c test,
which tests for the proportion of hemoglobin in red blood cells that has glucose stuck
to it - called glycated hemoglobin.
HbA1c levels of 5.7% to 6.4% indicates prediabetes, and 6.5% or higher indicates diabetes.
This proportion of glycated hemoglobin doesn’t change day to day, so it gives a sense for
whether the blood glucose levels have been high over the past 2 to 3 months.
Finally, we have the C-peptide test, which tests for this byproduct of insulin production.
If the level of C-peptide is low or absent, it means the pancreas is no longer producing
enough insulin, and the glucose can’t enter the cells.
For type I diabetes, insulin is the only treatment option.
For type II diabetes, on the other hand, lifestyle changes, like weight loss and exercise, along
with a healthy diet and oral antidiabetic medications, like metformin and several other
classes, can sometimes be enough to reverse some of that insulin resistance and keep blood
sugar levels in check.
However, if oral antidiabetic medications fail, type II diabetes can also be treated
with insulin.
Something to bear in mind is that insulin treatment comes with a risk of hypoglycemia,
especially if insulin is taken without a meal.
Symptoms of hypoglycemia can be mild, like weakness, hunger, shaking, but they can progress
to loss of consciousness and seizures in severe cases.
In mild cases, drinking juices, or eating candy, or sugar, may be enough to bring blood
sugar up.
But in severe cases, intravenous glucose should be given as soon as possible.
The FDA has also recently approved intranasal glucagon as a treatment for severe hypoglycemia.
Ok, now, over time, high glucose levels can cause damage to tiny blood vessels, called
the microvasculature.
In arterioles, a process called hyaline arteriolosclerosis where the walls of arterioles where they develop
hyaline deposits, these deposits of proteins, and these make them hard and inflexible.
In capillaries, the basement membrane can thicken and make it hard for oxygen to easily
move from the capillary to the tissues, causing hypoxia.
One of the most significant effects is that diabetes increases the risk of medium and
large arterial wall damage and subsequent atherosclerosis, which can lead to heart attacks
and strokes, major causes of morbidity and mortality for patients with diabetes.
In the eyes, diabetes can lead to retinopathy and evidence of that can be seen on a fundoscopic
exam that shows cotton wool spots or flare hemorrhages - and can eventually cause blindness.
In the kidneys, the afferent and efferent arterioles, as well as the glomerulus itself
can get damaged which can lead to a nephrotic syndrome that slowly diminishes the kidney’s
ability to filter blood over time - and can ultimately lead to dialysis.
Diabetes can also affect the function of nerves, causing symptoms like a decrease in sensation
in the toes and fingers, sometimes called a stocking-glove distribution, as well as
causing the autonomic nervous system to malfunction, and that system controls a number of body
functions - everything from sweating to passing gas.
Finally, both the poor blood supply and nerve damage, can lead to ulcers (typically on the
feet) that don’t heal quickly and can get pretty severe, and need to be amputated.
These are some of the complications of uncontrolled diabetes, which is why it’s so important
to, diagnose and control diabetes through a healthy lifestyle, medications to reduce
insulin resistance and even insulin therapy if beta cells have been exhausted.
While type 1 diabetes can not be prevented, type 2 diabetes can.
In fact, many people with diabetes can control their blood sugar levels really effectively
and live a full and active life without any of
the complications.
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