Download Diabetes - ClassNet

DIABETES
Also known as Diabetes Mellitus, it is a group of metabolic diseases in which a person has
chronically high blood glucose levels (high blood sugar). This high blood sugar produces the
symptoms of frequent urination, increased thirst and increased hunger.
If left untreated or simply ignored, diabetes can cause many complications. Acute
complications include ketoacidosis and coma. Long-term complications can include heart
disease, kidney failure, and damage to the eyes and tissues at the extremities (mainly toes and
feet).
Diabetes is a result of either a lack of insulin production or under-production by the beta cells of
the pancreas or because cells of the body lose sensitivity to the insulin that is produced. In both
cases, the result is an excess of glucose in the blood as the body’s tissues are unable to transport
glucose across the cell membrane for use as energy.
There are three main types of diabetes mellitus:
Type 1 DM results from the body's failure to produce insulin. This form was previously
referred to as "insulin-dependent diabetes mellitus" (IDDM) or "juvenile diabetes"
because it is usually diagnosed in children. Type I Diabetes includes latent autoimmune
diabetes in adults, which results when the T-Cells of a person’s immune system attack
and damage or destroy the beta cells on the Islets of Langerhans of the pancreas. About
10% of people with diabetes are this type. Type I diabetes is partly inherited with
multiple genes known to increase the risk. Onset can be triggered by one or more factors
including viral infection or diet.
Type 2 DM results from insulin resistance, a condition in which cells fail to use insulin
properly, sometimes also with an absolute insulin deficiency. This form was previously
referred to as non-insulin-dependent diabetes mellitus (NIDDM) or "adult-onset
diabetes". Type 2 diabetes is due primarily to lifestyle factors and genetics. Obesity,
lack of physical activity, poor diet and stress are the leading risk factors. In early stages,
therapeutic drugs which improve insulin sensitivity of the body’s tissues or reduce
glucose production by the liver can help to reduce hyperglycemia.
Gestational diabetes, is the third main form and occurs when pregnant women without a
previous diagnosis of diabetes develop a high blood glucose level.
While diabetes is a serious disease, identifying the symptoms early greatly increases the
prospects for a healthy, relatively normal life for diabetic patients. Signs and symptoms in
children include:
 Drinking and urinating more
 Bedwetting
frequently than usual
 Lack of energy
Other signs and symptoms include:





Unusual thirst
Frequent urination
Sudden or unusual weight gain/loss
Extreme fatigue/lack of energy
Blurred vision



Frequent or recurring infections
Cuts and bruises that are slow to heal
Tingling or numbness in hands and
feet
Blood sugar/blood glucose levels are typically used to test for pre-diabetes or diabetes. In
general, blood glucose concentrations greater than 7.0mmol/L are higher than normal and cause
for concern. Readings are normally taken after the person has fasted (nothing to eat or drink) for
about 8 hours. This generally allows enough time for the body to convert excess glucose in the
blood to glycogen for storage in the liver.
Patients with undiagnosed or untreated diabetes may suffer from ketoacidosis, a condition
which results from a shortage of insulin. Without glucose to power the cell’s metabolic
processes, the cells will switch to metabolizing fatty acids. This produces acidic ketone bodies
as metabolic waste products. Symptoms of ketoacidosis are nausea, vomiting, excessive thirst,
panting or deep gasping breathing, excessive urine production and severe abdominal pain, along
with severe hyperglycemia. A patient may have “ketone breath”, a fruity odour resulting from
the volatile nature of ketones (they evaporate in air – which happens when blood saturated with
ketones circulates through the lungs). Patients with ketoacidosis may also seem confused,
lethargic or may fall unconscious. Diabetic ketoacidosis is a medical emergency and can lead to
death if untreated.
Diabetic ketoacidosis arises because of a lack of insulin in the body. The lack of insulin and
corresponding elevation of glucagon leads to increased release of glucose by the liver (a process
that is normally suppressed by insulin). High glucose levels spill over into the urine, taking
water and dissolved sodium and potassium along with it in a process known as osmotic diuresis.
This leads to dehydration, and extreme thirst. The absence of insulin also leads to the release of
free fatty acids from adipose tissue which are converted, again in the liver, into ketone bodies.
These can serve as an energy source in the absence of insulin-mediated glucose delivery and is a
protective mechanism in case of starvation. The ketone bodies however, turn the blood acidic
(metabolic acidosis). The body initially buffers the change with the bicarbonate buffering
system, but this system is quickly overwhelmed and other mechanisms must work to compensate
for the acidosis. One such mechanism is hyperventilation to lower the blood carbon dioxide
levels. Untreated, ketoacidosis can cause cerebral edema (brain swelling) which can cause
headache, coma, loss of the pupillary light reflex and death. Blood glucose levels in patients
with ketoacidosis usually exceed 13.8mmol/L.
Coma, or more specifically, hyperosmolar hyperglycemic coma results when high blood
glucose levels result in extreme dehydration. The major difference between a patient in a
hyperosmolic hyperglycemia state (HHS) and ketoacidosis is that blood glucose levels in HHS
are extremely high, greater than 40-50mmol/L. The increasing glucose concentration and
resulting volume depletion due to excess kidney function may result in:



Altered mental status
Sensory or motor impairment
Increased thirst



Tremors or depressed reflexes
Heart attack or stroke
Death
All forms of diabetes increase the
risk of long-term complications.
These complications typically
develop after many years (10–20),
but may be the first signs or
symptoms in those who have
otherwise not received a diagnosis
before that time.
The major long-term
complications relate to damage to
blood vessels. These complications
can be grouped into microvascular
disease (damage to small blood
vessels) and macrovascular disease
(damage to larger arteries).
The primary microvascular
complications of diabetes include
damage to the eyes, kidneys, and
nerves. Damage to the eyes, known
as diabetic retinopathy, is caused by
damage to the blood vessels in the retina of the eye, and can result in gradual vision loss and
potentially blindness. Damage to the kidneys, known as diabetic nephropathy, can lead to tissue
scarring, urine protein loss, and eventually chronic kidney disease, sometimes requiring dialysis
or kidney transplant. Damage to the nerves of the body, known as diabetic neuropathy, is the
most common complication of diabetes. The symptoms can include numbness, tingling, pain,
and altered pain sensation, which can lead to damage to the skin. Diabetes-related foot problems
(such as diabetic foot ulcers) may occur, and can be difficult to treat, occasionally requiring
amputation.
The primary macrovascular complications of diabetes include coronary artery disease (angina
and myocardial infarction), stroke, and peripheral vascular disease. About 75% of deaths in
diabetics are due to coronary artery disease.
The HPA axis is an integral part of the neuroendocrine system with an important role in
maintaining homeostasis under varying physical and psychological stresses encountered by the
body. The HPA axis regulates the production and release of glucocorticoid (GR) hormones by
the adrenal glands. Under normal conditions, the activity of the HPA axis is regulated by the
day/night cycles of the body’s circadian rhythms. It’s a complex web of interaction in which the
hypothalamus secretes CRF and vasopressin which then stimulates the pituitary gland to release
ACTH, which in turn activates glucocorticoid production in the adrenal cortex.
Besides being regulated by circadian rhythm, the HPA Axis is also the major system that
responds to stress. It’s part of the homeostatic control mechanism that provides resistance to
changes in the body’s environment. When subjected to stress, affected regions of the brain
activate the amygdala (a key component of the limbic system that coordinates negative
emotional responses to threatening stimulus) which triggers the hypothalamus, leading to HPA
axis activation and glucocorticoid production. Glucocorticoids affect energy metabolism and
cardiovascular responses by preparing tissues for the physical needs that may be needed for the
body to respond to stress. They can also suppress immune and neurological function.
HPA axis activity is regulated by a glucocorticoid(GR) negative feedback mechanism involving
the hypothalamus and pituitary gland. GR acts on the hypothalamus to suppress CRF and ACTH
production which should restore homeostasis. However in situations in which there is long-term
stress, the HPA axis can become “hyperactivated”, overwhelming the feedback mechanism and
disrupting metabolic systems in similar ways as with diabetes. Patients with Type I diabetes
typically present increased activity of the HPA axis, resulting in increased levels of
glucocorticoids and other complications related to diabetes including hypertension, immune
suppression and increased risk of depression. One explanation for the hyperactivity of the HPA
axis in diabetics is the chronic effect of hyperglycemia-induced stress as chronically high blood
glucose levels induce an increase in glucocorticoid production.
A reduction in insulin levels characterizes Type 1 diabetes and diabetes also increases glucagon
levels as the body tries to reduce blood glucose. However, increased glucagon levels also
activate the HPA axis. As a result, increased levels of glucagon in diabetic patients can also
contribute to the overproduction of glucocorticoids which culminate in the development or
aggravation of diabetic complications.
Resources:
1. http://www.diabetes.ca/
2. http://en.wikipedia.org/wiki/Diabetes_mellitus
3. http://omicsonline.org/from-type-1-diabetes-hpa-axis-to-the-disease-complications-21556156.S12-002.pdf
QUESTIONS:
1. What types of cells on the pancreas are responsible for insulin production? Where,
exactly are they located?
2. What causes Type 1 diabetes?
3. What are the most common symptoms of diabetes?
4. If left untreated, diabetic hyperglycemia can result in two progressively more severe
conditions. What are they? How is each characterized?
5. What is the approximate blood glucose level that defines diabetes?
6. What long-term complications can result from diabetes?
7. What is the danger of chronic glucocorticoid overproduction? How is this linked to
diabetes?
8. The connection between diabetes, the stress response and the HPA Axis has only very
recently been identified. A disease called Cushing Syndrome has also been linked to
both HPA dysfunction and diabetes. Using your textbook, find out what Cushing
Disease/Cushing Syndrome is.
9. Using the internet at home, research Cushing Syndrome/Cushing Disease more
thoroughly and identify the signs, symptoms, tests and treatments for the disease.
10. Investigate the connection between long-term exposure to stress and dysfunctional HPA
axis. Are there any similarities between the effects of diabetes and long-term stress on
the HPA axis?