Compare and contrast type 1 and type 2 diabetes in regard to etiology, natural history, and pathogenesis.
o Type 1 Diabetes
10% of the diabetic population
Usually occurs in adolescence or young adulthood
Can occur at any age
Pathophysiology:
Immune-mediated
Type 1 DM ...
RUSH UNIVERSITY COLLEGE OF NURSING
NSG 533--ADVANCED PATHOPHYSIOLOGY
Endocrine Disorders – 17 questions
Compare and contrast type 1 and type 2 diabetes in regard to etiology, natural history, and pathogenesis.
o Type 1 Diabetes
10% of the diabetic population
Usually occurs in adolescence or young adulthood
Can occur at any age
Pathophysiology:
Immune-mediated
Type 1 DM is a slowly progressive autoimmune T cell-mediated disease that occurs in
genetically susceptible individuals
Causes destruction of pancreatic β-cell
o Lymphocyte and macrophage infiltration of the islets resulting in inflammation
(insulitis) and islet β-cell death
o Production of autoantibodies against islet cells, insulin, glutamic acid
decarboxylase (GAD) and other cytoplasmic proteins
Non-immune-mediated
No identified cause
Very small number of cases
Genetic Susceptibility
Concordance rate for type 1 DM is greater in monozygotic than dizygotic twins
In Caucasians, the risk in type 1 DM is 0.2-0.3%
If an individual has type 1 DM, the risk is approximately 5% among his/her siblings
Risk is 3% if mother has the disease
Risk is 6% if father has the disease
Risk is 30-50% for the identical twin of sibling with type 1 DM
The major genetic predisposition appears to be conferred by diabetogenic genes on
the short arm of chromosome 6, either within or in close proximity to the MHC
region, or the human leukocyte antigen (HLA) region
Autoimmunity
Evidence to strongly suggest autoimmunity
o Presence of autoantibodies
o Islet cell antibodies
o Insulin autoantibodies
o Clinical trials of immunosuppressive therapy (e.g. cyclosporine) demonstrated
temporary preservation of Beta-cell function in newly diagnosed type 1 DM
Insulitis
o “Lymphocyte-rich inflammatory infiltrate” noted in pancreas of those newly
diagnosed
o Consistent of other autoimmune processes and establishing a role of T-cell
autoimmunity
Evidence of cell mediated immune process
o Destruction of B-cells mediated by cytokines, produced by cells such as
lymphocytes
Environmental
What environmental factor is the “triggering” event
, Is it Viruses ????????
o Enteroviruses & H. pylori
Does the viral protein contain an amino acid sequence similar to a Beta cell protein?
o This molecular mimicry initiates an immune response w/ destruction of B-cells
Does the virus damage a Beta -cell?
o This initiates an immune response against antigens in virally altered B-cells
with destruction of B-cells
Type 1 diabetes is the result of the human immune system mistaking the body’s beta cells,
which produce insulin, for foreign cells and causing their destruction. Insulin is a protein that
allows the transport of sugar into cells to provide energy. When sugar can’t get from the blood
into the cells, the cells have no access to the glucose they need and cannot function correctly.
The composition of our blood also gets off balance, with high blood sugar levels leading to
detrimental effects on other organs of the body. Injecting synthetic insulin solves this problem
because it keeps blood glucose levels in the right range and helps glucose reach our cells
Treatment:
Diet
Exercise
Insulin
Primarily associated with Type 1 Diabetes: Diabetic ketoacidosis (DKA)
o Type 2 Diabetes
90% of the diabetic population
Usually occurs in midlife
Pathophysiology:
Insulin resistance (insulin normally binds to cell surface receptors)
The binding may be impaired
There may be less receptors
There may be post-receptor defects
Defect in pancreatic β-cell secretion
Treatment:
Diet
Exercise
Oral medications and/or insulin/incretins
Primarily associated with Type 2 Diabetes: Hyperglycemic Hyperosmolar (HHS)
Patients with type 2 diabetes make insulin, but the cells in the body cannot respond to it
adequately so they cannot take up glucose. Later on, especially when treatment fails, type 2
diabetes is aggravated by exhausted beta cells, decreasing their insulin production resulting in
further increases in blood sugar levels. Since beta cells aren’t killed off in type 2 diabetes, at
least initially, blood sugar levels often become elevated at a slower rate than with type 1
diabetes. This means that someone can have high blood sugar for quite sometime without
realizing it, and may only find out they have type 2 diabetes when complications of diabetes
appear, such as damage to eyes, the kidney and nerves. Additionally, this means that treatment
for type 2 diabetes varies from case to case. While insulin therapy is needed for some people
with type 2 diabetes, others are able to use alternative medications. Lifestyle changes such as
diet and exercise have also been known to help type 2 diabetes and are always recommended
, for those with the disease.
List the classic symptoms of diabetes mellitus. (Type 1)
o Polydipsia (increased thirst)
Because of elevated blood glucose levels, water is osmotically attracted from body cells,
resulting in intracellular dehydration and hypothalamic stimulation of thirst
As fluid from the body tissues is reduced and runs through osmosis into the bloodstream
there is a call for more fluids to avoid dehydration at the cellular level. This means that
your brain gets the signal to drink more water as the body feels thirsty.
The excessive sugar buildup in the body is dumped into the kidney and body needs more urine
to get rid of the sugar. This means that the diabetic person needs to drink more fluids to flush
out the sugar that is deposited in the kidneys and so they tend to feel extra thirsty. So both
reasons increase the level of thirst in a diabetic person to higher than that of a healthy person.
o Polyuria (frequent urination)
Hyperglycemia acts as an osmotic diuretic; the amount of glucose filtered by the glomeruli of
the kidneys exceeds the amount that can be reabsorbed by the renal tubules; glycosuria results,
accompanied by large amounts of water lost in the urine
Polyuria happens because as the blood sugar level in the body rises there is an increase in the
osmosis rate of the blood. This results in the drawing out the fluid from the tissues into the
bloodstream. This does not help decrease the blood sugar level but does dilute it to a level
where it is acceptable to the rest of the body’s cells.
Now all this excess fluid in the bloodstream is cleaned out by the kidneys. This results in the
bladder becoming full with urine and so you need to go empty the bladder to relieve the
pressure you feel by urinating.
o Polyphagia (increased hunger)
Depletion of cellular stores of carbohydrates, fats, and protein results in cellular starvation and a
corresponding increase in hunger
Body thinks its starving because it is unable to use glucose stores
o Weight loss
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