Pathophysiology of Diabetes

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Diabetes is a chronic metabolic disorder in
which the body cannot metabolize
carbohydrates, fats, and proteins because
of a lack of, or ineffective use of, the
hormone insulin.

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 I. Type 1 (IDDM) or juvenile- onset diabetes)

A. Causes
– 1. Genetic predisposition.
– 2. Environmental exposure: virus, toxin, stress.
– 3. Autoimmune reaction: beta-cells that pro-
duce insulin in the pancreas are destroyed.
When 80-90% of the beta-cells are destroyed,
overt symptoms occur.

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B. Characteristics
– 1. Usually occurs before 30 years of age, but
can occur at any age. Peak incidence occurs
during puberty, around 10-12 years of age in
girls and 12-14 years in boys.*
– 2. Abrupt onset of signs and symptoms of
hyperglycemia: increased thirst and hunger,
frequent urination, weight loss, and fatigue.
– 3. Ketosis prone.

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II. Type 2 (NIDDM, or adult-onset diabetes)

A. Causes
– 1. Insulin resistance: unable to utilize insulin that the
body makes because of cell-receptor defect; glucose
is unable to be absorbed into cells for fuel.
– 2. Decreased insulin secretion: pancreas does not
secrete enough insulin in response to glucose levels.
– 3. Excess production of glucose from the liver: result
of defective insulin secretory response.

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B. Characteristics
– 1. Usually occurs after 30 years of age, but is now
occurring in children and adolescents..
– 2. Strong genetic predisposition.
– 3. Frequently obese.
– 4. Not prone to ketoacidosis until late in course or
with prolonged hyperglycemia.
– 5. May or may not have symptoms of hyperg-
lycemia.
– 6. May also have extreme tiredness, blurred vision,
delayed healing, numbness and tingling of hands and
feet, recurring yeast infection.
– 7. Children between the ages of 10-19 that have one
or more of the following are at an increased risk:
• Family history
• Member of certain ethnic populations listed above in B.2.
• Overweight
• Sedentary lifestyle
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 III. Gestational Diabetes Mellitus (GDM)
A. CAUSES
– 1. Insulin resistance due to pregnancy
– 2. Genetic predisposition
B. Characteristics
– 1. Carbohydrate intolerance during pregnancy
identified via 1-hour screen using a 50-g oral glucose
load (performed between 24th and 28th week of
gestation unless otherwise indicated). If the 1-hour
screen for glucose is >140 mg/dl (>7.8 mmol/l), a full
diagnostic 100-g, 3-hour oral glucose tolerance test
(OGTT) is indicated.

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In the fasting state, if nothing happened to
prevent it, blood glucose would start to go down.
The normal physiology of the fasting state is to
secrete some glucagon and keep hepatic
glucose output high enough to keep blood
glucose from falling into the hypoglycemic
range. Insulin levels then fall to a basal level. As
a result, blood glucose tends to stay up.
In the fed state, the glucagon effect is dampened
and the insulin effect is amplified so that blood
glucose is reduced. This is normal physiology.

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If you have type 2 diabetes, you have too
much alpha-cell function, meaning too
much glucagon moving glucose out of the
liver, and you do not have enough insulin
activity to stimulate uptake of glucose in
muscle and adipose tissue. Keep that in
mind when you think about what the
incretins are going to do.

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 SCREENING TEST

Urine Glucose
Fasting Blood Sugar
Two – Hour Postprandial Blood Glucose

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 Diagnostic Tests
Oral Glucose Tolerance Test ( OGTT)
IV GTT

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A glucose tolerance test in medical
practice is the administration of glucose to
determine how quickly it is cleared from
the blood.
The glucose is most often given orally so
the common test is technically an oral
glucose tolerance test (OGTT).

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Normal fasting plasma glucose is less than
100 mg/dL; in a 2-hour glucose tolerance
test, the 2-hour value should be less than
140 mg/dL. We diagnose diabetes if either
the fasting blood glucose is above 126
mg/dL on two occasions, or the 2-hour
glucose tolerance test is above 200
mg/dL.

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 1999 WHO Diabetes criteria - Interpretation of Oral Glucose Tolerance Test

Impaired Fasting Impaired Glucose Diabetes

Glucose Glycaemia Tolerance Mellitus
NORMAL
levels
(I.F.G.) (I.G.T.) (D.M.)

Venous
Fasting 2hrs Fasting 2hrs Fasting 2hrs Fasting 2hrs
Plasma
> 6.1 &
(mmol/l) <6.1 <7.8 <7.8 <7.0 >7.8 >7.0 >11.1
<7.0

>110 &
(mg/dl) <110 <140 <140 <126 >140 >126 >200
<126

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In addition, other studies have shown that
impaired glucose tolerance increases the
mortality rate in the population. This slide
looks at the mortality hazard over a 10-
year period in about 25,000 people in
different categories of glucose tolerance,
normal being on the bottom with the least
mortality. The worst mortality hazard is in
those individuals who have diagnosed
diabetes
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