Download Diabetes Mellitus

Diabetes Mellitus
Sean Ragain MD
What does ‘diabetes’ actually
mean?
 The
word has many origins, and the
medieval latin word diabetes means
to ‘go through’ or ‘pass over’.
 Why do you suppose this definition
made it an adequate word for the
various diseases termed ‘diabetes’?
Diabetes
 Today,
we’ll focus on diabetes
mellitus and its subtypes because
this is what you will see probably
every day.
 Who knows the other type of
diabetes? And what is its cause?
Diabetes insipidus
Who
remembers
this from
anatomy?
 What happens
when ADH
(vasopressin)
production is
compromised?

Diabetes insipidus
 Fairly
rare, has two subtypes.
 First type is called central diabetes
insipidus because this is a problem of
ADH secretion. May be a problem
with the hypothalamus or pituitary
gland, and has many potential
causes. What do you think could
cause such a defect?
Diabetes Insipidus
 Central
DI can be caused by tumor,
injury, infection, autoimmune
process.
 Second type is nephrogenic, meaning
the problem is at the kidney level.
Usually associated with other obvious
renal disease. Ex. CRF, sickle cell
disease, lithium/cochicine toxicity.
Diabetes Insipidus
 Causes
massive polyuria and
polydipsia
 May lead to hypernatremia,
hypotension, and even shock.
 Central diabetes can be fairly easily
treated with intranasal DDAVP.
 Nephrogenic DI is more difficult to
treat, and usually involves treating
the underlying renal disease.
Diabetes Mellitus
 Not
a problem
with ADH, but
a problem with
insulin!!
Diabetes Mellitus
Type I and Type II
 Type I is considered “childhood” or
“insulin-dependent” diabetes, and its
symptoms tend to be more extreme than
type II.
 Prevalence is 1 in 600 in USA and Europe,
much less so in Asia for example.
 Until the 1920’s, this disease was fatal,
and led to a long-suffering and miserable
death.

Diabetes Mellitus, history lesson

Canadian researchers
Frederick Banting and
Charles Best
discovered that
pancreas extract could
lower blood sugar
levels in dogs whose
pancreas had been
removed. This was
soon used on humans
with astounding
results. They received
the Nobel Prize in
1923 for this work,
and few would deny
the impact of their
achievements.
The Pancreas
Endocrine Pancreas
Pancreas
 Both
an endocrine and an exocrine
organ. In fact, 99% of the pancreas
tissue takes part in exocrine
function, leaving 1% for endocrine.
 Wedged in between the acini and
ducts are the islets of langerhans,
which contain alpha, beta, and delta
cells. Which produce insulin?
Pancreas
 The
beta cells produce insulin
 The alpha cells produce glucagon
 The delta cells produce somatostatin
What is normal pancreas endocrine
function?
Increases in blood glucose (after eating)
causes release of insulin from beta cells.
 Insulin stimulates cells of the body to
increase entry of glucose. This is
particularly important in muscle, fat, and
liver cells.
 Glucose levels are returned to “normal”.
 When insulin levels drop, glucagon is
secreted, which causes release of glucose
from areas of storage (liver, muscle etc.).

Balance of
insulin and
glucagon


Maintains a normal
set point for
glucose
concentration at all
times
What are symptoms
of hypoglycemia?
What’s the difference between
Type I and Type II?
Type I is usually acquired earlier in life,
but can occur at any time. It results from
destruction of the beta cells of the
pancreas. What does this do?
 Type II is usually acquired later in life, and
is associated with obesity, sedentary
lifestyle etc. This is a combination of
resistance to insulin, and slight decrease
of insulin production. The beta cells are
impaired, not destroyed (non-insulindependent diabetes).

When someone presents to the ER
with a diabetic crisis, what is the
typical picture?
 Of
course, it depends, but
presentation of type I is often
dramatic, and may lead to
ketoacidosis.
 Ketoacidosis is associated with type
I, but can occur in untreated type II
as well.
Ketoacidosis
If beta cells are destroyed, insulin levels
may drop to nearly zero.
 When this happens, glucose levels
drastically rise. Why?
 Not only is there a rise in blood glucose
(which is bad enough), but the cells are
not getting an energy source, because
they aren’t being stimulated to allow
glucose in.
 Therefore, some texts refer to diabetes as
starvation in the midst of plenty.

Ketoacidosis
So, without glucose, the cells of the body
start to use alternative fuels, such as fats,
glycogen, and proteins to produce energy.
 This is ok in the short term, and in fact,
occurs in all of us to some degree,
especially during intense exercise, or
periods of brief starvation.
 However, without insulin, this continues,
and in a short period can lead to severe
symptoms. What symptoms can you think
of?

Ketoacidosis
A
byproduct of fat metabolism is
ketone bodies.
 These lead to increased acidity in the
bloodstream, which causes a natural
drop in blood pH.
 These individuals will often have a
sweet, almost fruity odor to their
breath known as acetone breath.
Ketoacidosis
How does a person compensate for a drop
in pH, especially in the short term?
 Kussmaul breathing!!!
 Tachypnea and hyperpnea, an attempt to
bring pH back to normal by blowing off
CO2.
 Also, the kidneys will increase secretion of
hydrogen ion to increase pH.

Ketoacidosis
What are the consequences of all that
excess glucose?
 If glucose is above 170 mg/dL, the kidney
tubules will be unable to reabsorb glucose
adequately, leading to glucosuria. Also,
this added solute in the glomerular filtrate
draws more water into the urine, causing
polyuria.
 This in turn leads to extreme thirst and
dehydration.

Ketoacidosis
How do most people with type II
diabetes present?
Again, this depends, and if the person
never sees a doctor, they may present in
ketoacidosis. Usually, they are diagnosed
by routine blood tests for glucose.
 This test is only considered diagnostic if a
person is fasting 12 hrs before blood is
drawn.
 The WHO considers a fasting glucose level
above 126 mg/dL to be diagnostic for
diabetes mellitus.

Diagnosis and monitoring
A
very helpful adjunct test for
diabetics is the level of Hemoglobin
A1C (glycosylated hemoglobin). This
is a better indicator of long-term
glucose levels, as hemoglobin
becomes stongly bonded to excess
glucose molecules. Normal Hgb A1C
should be below 6% of total Hgb.
With poor control, this number will
rise.
Type II diabetes mellitus
Again, this is usually a combination of
insulin resistance at the cellular level, and
some impairment of insulin production.
 Without going into unnecessary detail, it is
sufficient to know that many years of poor
eating/exercising habits along with excess
body fat leads to overproduction of insulin.
Eventually, the beta cells tire out.
 Also, constant exposure to high levels of
insulin causes cells to downregulate their
insulin receptors. What does that mean?

Type II diabetes mellitus
 Decreased
production and resistance
at the cellular level causes a wide
variety of glucose abnormalities.
 Often, the patient feels just fine,
which may lead to poor compliance
with medications and
recommendations.
Symptoms of Diabetes
 Many
of the
symptoms of
type II
diabetes are
a result of
long-term
elevated
glucose
levels.
Call social services?
Symptoms and consequences of
long-term hyperglycemia

Vascular disease
–
–
–
–
Myocardial infarction
Stroke
PVD
Impotence
Neuropathy
 Retinopathy
 Renal Disease
 Skin disease
 Gastroparesis

Diabetic Neuropathy

Neuropathic Ulcers, may
lead to amputation!!
Diabetic Neuropathy
 What
is a
bacteria that
loves diabetic
ulcers?
Transtibial Amputation
Diabetic Retinopathy
Diabetic Retinopathy
Gastroparesis
 All
neurons of the body are affected
by high blood sugar, including
autonomic neurons!!
 The gut may become partially
paralyzed, which can lead to nausea,
vomiting, diarrhea, constipation (you
name it!).
What do the stats say?
2
out of 3 diabetics die from heart
disease or stroke!!!
 Quality of life is greatly reduced in
untreated diabetes mellitus (type II).
Treatment
Lifestyle changes – most bang for the
buck, most difficult to implement. A lot of
personal glucose monitoring is required to
titrate medications. Patients may keep a
log of glucose levels at various times of
the day, write them down, and bring these
logs to doctor visits.
 Insulin – injections, pumps, pens. Usually
for type I, but may be needed in severe
type II. This is life-saving for type I
patients!

Types of Insulin
 NPH
 Humalog
 Novolog
 Apidra
 Lantus
Treatment
Sulfonylureas –
Increase insulin
release from the
endocrine pancreas,
and decrease glucose
production by liver.
Will this help type I
patients?
 Examples –
acetohexamide,
chlorpropamide,
glipizide, glimepride.

Treatment
 Biguanides
– Example – Metformin. Decreases
hepatic glucose output. This is similar
to the action of sulfonylureas, without
increasing insulin secretion. This is
sometimes preferable when patients on
sulfonylureas experience hypoglycemia.
Treatment
 Acarbose
– Decreases absorption of
starch and disaccharides in the gut.
 Doesn’t affect insulin secretion or
insulin sensitivity in the tissues.
Treatment
 Finally,
the Glitazones
– Including troglitazone and rosiglitazone.
– Increases the sensitivity of cells to
insulin.
The End