What is Diabetes Mellitus?

Diabetes mellitus is a common disease where there is too much sugar (glucose) floating
around in your blood. This occurs because either the pancreas can’t produce enough insulin
or the cells in your body have become resistant to insulin.

How does your body normally regulate glucose?

When you eat food, the amount of glucose in your blood skyrockets. That’s because the
food you eat is converted into glucose (usable energy for your cells) and enters your blood
to be transported to your cells around the body. Special cells in your pancreas sense the
increase of glucose and release insulin into your blood. Insulin has a lot of different jobs,
but one of its main tasks is to help decrease blood glucose levels. It does this by activating
a system which transports glucose from your blood into your cells. It also decreases blood
glucose by stimulating an enzyme called glycogen synthase in the liver. This molecule is
responsible for making glycogen, a long string of glucose, which is then stored in the liver
and used in the future when there is a period of low blood glucose. As insulin works on
your body, the amount of glucose in the blood slowly returns to the same level it was before
you ate. This glucose level when you haven’t eaten recently (called fasting glucose) sits
around 3.5-6 mmol/L (70-110 mg/dL). Just after a meal, your blood glucose can jump as
high as 7.8mmol/L (140 mg/dL) depending on how much and what you ate.

Schematic of normal insulin regulation

What happens in diabetes mellitus?
There are two types of diabetes mellitus, type 1 and type 2. In both types, your body has
trouble transporting sugar from your blood into your cells. This leads to high levels of
glucose in your blood and a deficiency of glucose in your cells. The main difference
between type 1 and type 2 diabetes mellitus is the underlying mechanisms that cause your
blood sugar to stray from the normal range.

Type 1 DM:

Type 1 diabetics suffer from a complete lack of insulin in their bodies. Although the exact
cause has not been identified, it is clear that the cells which make insulin are destroyed by
the body’s own immune system. This occurs due to autoimmunity, a process by which the
immune system believes some of the body’s cells are foreign and targets them for
destruction. Eventually, the body destroys all of these cells and the symptoms of diabetes
manifest.

Schematic of insulin regulation with Type 1 Diabetes

Type 2 DM:

People with type 2 diabetes can still make insulin, but their cells have some degree of
insulin resistance. Type 2 diabetes is a continuum which begins with insulin resistance and
can end in loss of insulin secretion. When cells initially become resistant to insulin, the
body increases the amount of insulin made to counteract this effect and keep glucose levels
in a normal range. In fact, early type 2 diabetics have higher levels of insulin in their body
than non-diabetics. Eventually, the body cannot compensate enough, and blood glucose
levels begin to rise. The pancreatic cells begin working overtime to produce more and more
insulin and eventually burn out. As type 2 diabetes continues to progress, patients have to
start taking insulin to ensure they have enough of the molecule in their body.

Schematic of insulin regulation with Type 2 Diabetes

What are the symptoms of diabetes mellitus?
Initial symptoms:

Type 1: The classic initial presentation of type 1 diabetes is increased thirst, increased
urination, weight loss, hunger due to starvation of cells, and fatigue. As blood glucose
levels increase, the body tries to remove excess glucose in the urine and dilute the blood
by increasing water intake. However, many patients are initially diagnosed when they come
to the hospital very sick in a state called diabetic ketoacidosis. This occurs when cells use
alternative energy producing mechanisms, leading to high levels of byproducts called
ketoacids. Ketoacids acidify the blood, leading to dangerous acid-base disturbances.
Diabetic ketoacidosis causes abdominal pain, nausea/vomiting, and drowsiness and is a
potentially life-threatening condition.

Type 2: The symptoms of type 2 DM are similar to type 1, but generally occur later in life
and have a more gradual onset. 40% of patients have no symptoms. The other 60% can
present with increased thirst and urination, diabetic ketoacidosis, or a condition called
hyperosmolar hyperglycemic state, a state of severe dehydration requiring hospitalization.

Diagram of symptoms of diabetes mellitus

Long-term complications of Diabetes Mellitus:
Many of the major complications of diabetes, including coronary artery disease,
cardiovascular disease, peripheral vascular disease, and cerebrovascular disease are caused
by damage to large vessels in the body. High glucose levels lead to chronic inflammation
in the body, including the walls of the arteries in the blood. This chronic inflammation
leads to atherosclerosis, a buildup of a plaque with a fibrous cap on the walls of the arteries.
This narrows the arteries and leads to decreased blood flow in the arteries. In addition,
these plaques can rupture and lead to the formation of a blood clot which blocks off blood
flow. If this happens in the brain or the heart, it causes a stroke or a heart attack.

High blood glucose levels may also damage the smallest vessels in the body, leading to
multiple long-term microvascular complications. This damage both destroys the cells in
the blood vessels and leads to decreased blood flow and tissue death. Poorly controlled
diabetes can cause retinopathy (damage to the retina in the eyes, leading to blindness),
nephropathy (damage to the kidneys resulting in kidney failure), neuropathy (damage to
your nerves, which can cause numbness or tingling), and gastroparesis (dysfunction of your
digestive system causing chronic vomiting and abdominal pain). All of these symptoms
are caused by glucose-induced damage to blood vessels.

Diabetes has a large negative effect on the body’s immune system. High glucose levels
ramp up the activity of immune cells. These cells eventually become exhausted and
desensitized, decreasing their effectiveness against invading pathogens. Poorly controlled
diabetics are more prone to severe skin infections and have longer hospital stays for
infections like pneumonia or urinary tract infections.

How likely are you to get it?

It’s unclear who gets type 1 diabetes or how to prevent it. Given the main cause of type 1
diabetes is autoimmunity, environmental factors are likely the largest risk factor. Type 2
diabetes, on the other hand, is directly related to obesity and diet. Overweight individuals
become more and more resistant to insulin and are much more likely to get diabetes.
Physical fitness and a healthy diet are the most important aspects of type 2 diabetes
prevention. Both types of diabetes have genetic predispositions, with type 2 having a larger
genetic component to the disease.

How do you treat it?

The only effective treatment in type 1 diabetes is administering insulin as these patients no
longer produce it. There are many different types of insulin and different regimens but
many patients will use a long-acting insulin at night supplemented by a short-acting insulin
before meal times. Newer treatment regimens include the use of an insulin pump where
blood glucose levels are entered into a machine which then uses an algorithm to pump
insulin into the body.

Type 2 diabetics have more options. Initial therapy for type 2 diabetics with mild disease
is lifestyle modification: a healthy diet with exercise to help lose weight. If this fails, the
first medication used is typically Metformin, a drug which stops the liver from making
glucose in a process called gluconeogenesis. It also increases the number of insulin
receptors present on cells, so they become more sensitive to insulin. In between Metformin
and insulin therapy are a number of drugs which help increase the release of insulin from
the pancreas. These include sulfonylureas, a-glucosidase inhibitors, and glinides.

Consider the following:

Sometimes, pregnant women can develop diabetes while they are pregnant, a process called
gestational diabetes. This usually reverses once they give birth, but can persist after the
pregnancy. Gestational diabetes is similar to type 2 diabetes: the hallmark of this disease
is insulin resistance.

During the second trimester, pregnant women increase their resistance to insulin and have
higher blood sugar levels, likely to increase delivery of glucose to the fetus. Most women
increase the amount of insulin produced from the pancreas, but women with gestational
diabetes cannot produce enough and functionally become type 2 diabetics throughout their
pregnancy.

Diabetes can alter your body’s response to certain diseases. For example, diabetics who
have heart attacks are more likely to present with atypical symptoms (and oftentimes
present without chest pain altogether). This is likely partly due to nerve damage. Many
diabetics have peripheral neuropathy, a nerve condition where they feel constant numbness
and tingling in their toes and feet and have trouble recognizing pain in those limbs. These
patients likely have nerve damage to other parts of their body, including their heart. The
atypical symptoms lead to a delay in diagnosis of heart attacks.