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Due to inadequate production or utilization of insulin.

Major public health problem

because complications include HTN, hyperlipidemia, and can cause many serious
health problems.

More than 57 million American adults have prediabetes (fasting glucose of 100-125)
risk factor for diabetes and cardiovascular disease.
7th leading cause of death, affects 25.8 million people, additional 7 million people are
unaware that they have disease.

FBS greater than 100mg/100ml of blood is now considered indicative of insulin

resistance, risk for diabetic complications. 2 hour PP of 200mg/dl

55-60% carbohydrates (complexrice, pasta, whole grain foods, legumes)

20-25% fats
12-20% protein

Insulin is a hormone produced by the beta cells of the pancreas. Insulin is necessary
for the cells to use glucose.

Alpha cells secrete glucagon, which raises blood sugar by triggering the release of
glucose from cell storage cells.
Beta cells secret insulin, which lowers blood glucose. Insulin is secreted daily directly
into liver circulation, occurs within 10 minutes of eating.
Delta cells secrete somatostatin, which inhibits secretion of insulin, glucagon, and
growth hormone from pituitary gland.

Beta cells measure blood glucose levels (usually by the amount of ATP produced by
the mitochondria), then deliver the required amount of insulin for the glucose to enter
the cells.

Insulin stimulates the active transport of glucose into the cells

When insulin is absent, glucose cant enter most cellsremains in the bloodstream
Increased glucose in the blood increases osmolality, which stimulates the thirst center.

Think of each of the billions of cells in your body as tiny machines. Like all
machines, they need fuel. The foods you eat (carbohydrates, proteins, and fats) are
broken down to provide fuel for the cells, the mail fuel being glucose (a simple sugar).

Polyuria-water follows the glucose that is lost in the urine (spilled over)
Polydipsia-loss of water, leading to extracellular dehydration.
Polyphagia-chronic catabolism of fat and protein with relative cellular starvation.
Even with consumption of extra calories, weight loss frequently occurs.

These hormones are produced by separate, specialized cells of the pancreas-Islets of

Insulin released by beta cells of this area.
Insulin levels are low between meals.
Glycogenesis is conversion of glucose to glycogen, insulin promotes this process.

Endocrine=a gland that secretes directly into the bloodstream

Exocrine=a gland whose secretion reaches an epithelial surface either directly or
through a duct.
Exocrine secretion of pancreas secretes enzymes for digestion, sodium bicarbonate to
neutralize stomach acid.

Excess glucose is stored in the liver and muscles as glycogen. Free fatty acids are
stored as triglycerides in fat cells. When blood sugar is low, the liver glycogen is
released and transformed to glucose to be utilized.
In fasting state, insulin secretion is reduced, increased gluconeogenesis in the liver and
kidneys by the breakdown of liver glycogen.
When more glucose is present in liver cells then can be metabolized for energy or
stored as glycogen, insulin causes the excess glucose to be coverted to free fatty acids
which then convert to ketone bodies (provides backup energy source).

Absolute insulin deficiency=the pancreas produces no insulin, or very little insulin.

TYPE 1 diabetes
Relative insulin deficiency=pancreas produces either normal or excessive amount of
insulin, but the body is unable to utilize effectively. Glucose level is elevated. Also
known as insulin resistance. TYPE 2 diabetes

The pancreas initially produces more insulin, causing hyperinsulinemia. Even with
increased amount of insulin available, the cell receptors dont recognize it.
Insulin is also a growth factor, high levels trigger other problems associated with type
2 diabetes (endothelial dysfunction and atherosclerosis).

Glycagon is considered a couterregulatory hormone, elevated blood glucose levels.

Gluconeogenesis=conversion of amino acids into glucose. Breakdown of glycogen to

Lipolysis=fat breakdown
Proteolysis=protein breakdown

Elevated blood sugar


3 Ps
Abdominal pain
Increased rate of infections
Visual changes
changes in sensation

Weight loss

Low blood sugar (usually below 50)






Can be caused by insulin

Caused by the destruction of the beta cells, so insulin is missing.

Abnormal antibodies are found in these patients, so etiology is autoimmune. Can be
environmental trigger, such as a virus, which initiates the autoimmune process.

Onset-when insulin will begin to affect, go to work

Peak-when insulin is working the hardest, at the highest level.
Duration-length of time the insulin will be effective.
Regular, NPH, 70/30, Lantus, Humalog, Supra-lente
Rotating injection sites in same area allows similar absorption (abdomen fastest)

The amount of insulin is normal, BUT the tissues are resistant to it.
Insulin is defective or insufficient OR there is cellular insensitivity to insulin.

Possible that unidentified genetic trait causes the pancreas to secrete altered insulin, or
cause the insulin receptors or secondary messengers to fail to response to insulin.
Could be genetic link with obesity d/t prolonged stimulation of the insulin receptor
(possibly lead to decrease in the number of receptors on body cells)

The insulin secretion is often delayed, lessening the total amount released. This
worsens as the person ages.
Examples are:
Secretagogues (sulfonylurea agents)increases insulin secretion AMARYL and
Meglitinide Analogsincreases insulin secretion STARLIX
Biguanidesreduces hepatic glucose production and tissue sensitivity to insulin
Alpha-Glucosidase inhibitorsprevent postmeal elevation in glucose PRECOSE
Thiazolidinedionesimproves tissue sensitivity to insulin ACTOS AVANDIA
DPP4 Inhibitorsinhibit the enzyme that inactivates the incretin hormones=more
natural incretin hormones better regulate blood glucose (glucagon levels are decreased
and insulin secretion from pancreas beta cells is increased JANUVIA

Diagnosed with abnormal glucose tolerance test at 28 weeks.

In a high-glucose environment, a greater percentage of the hemoglobin is glycosylated

(sugar-coated cells, which causes them to function improperly)
The value reflects the average blood glucose level for the preceding 2-3 months, it can
evaluate long-term therapy effectiveness.

Insulin also stimulates protein synthesis and free fatty acid storage in adipose tissues.

Brain2.5 times more likely to have a stroke

Eyesleading cause of new adult blindness
Heart2-4 times more likely to have heart disease. 75% of diabetic deaths are related
to heart disease.
Kidneysleading cause of end-stage renal disease
Feet80% of lower limb nontraumatic amputations are diabetics. Most common
cause of peripheral neuropathy.

Worsened with increased carbohydrate consumption: metabolized into glucose and

fails to be utilized by liver and skeletal muscle, more elevated blood glucose levels
and glycosuria.

Microvascular changes occur to the small arterioles, capillaries and venules.

Macrovascular changes occur to the large and medium arteries, and all organs and
tissues of the body suffer as a result.
Microvascular complications are caused by the thickening of the basement membrane
of the small vessels. This thickening leads to ischemia, decreased passage of oxygen
and nutrients to tissues.
Macrovascular complications are caused by the development of atherosclerosis, leads
to poor blood flow.

CVA is especially true for type 2 diabetics d/t atherosclerosis. Which, combined with
HTN, weakens and can ultimately burst the vessels.
PVD occurs from severe atherosclerosis, contributes to need for amputations.
Impotence is often seen in long-term diabetics.

Diabetes is also associated with the development of cataracts and glaucoma.

The most serious vision loss is retinopathy (damage to the retina from loss of oxygen).
The retina uses a high amount of oxygen, and with chronic decreases of hypoxia, there
is breakdown in the capillary structure, microaneurysm formation, and spots of
hemorrhage. Then inflammatory system is activated, leads to scarring of the retina.
Interstitial edema occurs, and intraocular pressure rises.

Nephropathy from diabetes is the #1 cause of kidney failure in the U.S.

Damage to the glomerular capillaries caused by HTN and high plasma
glucosethickening of the basement membrane and glomerular enlargement.
Nodular, sclerotic lesions then develop among the glomeruli, blocking flow and
causing further damage.
First symptoms include spilling of urine protein, and if damage continues, ability to
secrete hydrogen ions decreases which affects acid-base balance (causes metabolic

DM damages the sensory and motor components, caused by chronic hypoxia of the
nerve cells as well as effects of hyperglycemia.
Demyelination damage causes slowing of the nerve conduction and loss of feeling.
Loss of temperature and pain sensation predisposes to unnoticed injury.
These injuries + poor blood flow + impaired immune system #1 cause of foot
amputations in the U.S. (other than trauma)

Early signs and symptoms include 3 Ps, headache, fatigue, anorexia (fat and protein
are depleted, loss of lean muscle mass)
Fat metabolism produces acidic substances called ketone bodies, accumulate and lead
to metabolic acidosis.

In response to insulin deficiency, the body uses fats and proteins to meet cellular
metabolic needs hyperglycemia, metabolic acidosis.

Increase in potassium as water moves out of cell and K+ moves with it.
When potassium moves back into the cells with insulin, places the patient at risk for