Let’s talk about the pathogenesis.
This is the most important called non-enzymatic
What does that mean?
With all that glucose that’s circulating,
it will then bind to protein.
It will cause and wreak havoc up and down
the body through depositing in the capillary
When it does so, it will cause arteriolosclerosis.
If it’s in the capillary, it will then cause
non-enzymatic glycosylation therefore compromise
proper exchange of nutrients.
Altered carbohydrate metabolism and a second
pathogenesis here is that you want to know
about sorbitol and that’s because with all
that glucose instead of going through the
glycolytic pathway, might end up going through
what’s known as aldose reductase.
With that aldose reductase and sorbitol, specifically
in the lens, remember what I told you?
If you start a patient with diabetes over
long period of time, what colour could that
In Greek, cataract means waterfall.
When you take a look at the waterfall, what
colour is that water when it’s falling over
Opaque and white, that’s what cataract means
in Greek, you find whiteness over the lens.
That’s because sorbitol accumulating in
the lens is going to cause waterfall, ha-ha,
into the lens.
In other words, increased osmotic pressure.
Unregulated glucose intake by these tissues
partially explains why these are the main
diabetes mellitus targets.
The increased glucose metabolized by the enzyme
aldose reductase to sorbitol.
That’s an important point, make sure you
pay attention to that enzyme.
Two major pathogeneses that I just walked
The most important would be non-enzymatic
glycosylation neg or you might have heard
of AGE, advanced glycosylate end-product,
one and the same; capillary membrane destruction.
Remember the arteriolosclerosis that you find
with diabetes, that’s called hyaline arteriolosclerosis
and do not forget about the sorbitol pathogenesis.
Quickly, type I versus type II, a brief, beautiful
summary of things that we’ve looked at.
In your head now, you should have a firm understanding
as to why these things are taking place.
Type I weight please… normal or thin; type
First step of management type II diabetic,
lose the weight.
Age type I… young; by young we mean still
less than 20 or 30 about 22, 23, but usually
younger, but you never know.
Remember the other differential that you want
to keep in mind called unconventional or MODY
in which is called Maturity Onset of Diabetes
in Young, in which I told you to focus upon
a deficiency in your glucokinase gene.
If it’s type II a little bit older, 30,
obese, insulin resistance.
Type I with glycaemic pattern all over the
place because of insulin pump; type II less
Insulin sensitivity… in type I, perfectly
normal hence the insulin pump; in type II,
if the receptors are not working, how in the
world is insulin even being properly responded
Insulin sensitivity reduced in type II.
What about oral agents?
Only effective in type II.
Antibody status… in type I, remember the
I told you about your glutamic acid decarboxylase,
a type II hypersensitivity, that’s autoimmunity,
so antibody status positive in type I, negative
in type II.
Remember the autoimmune disease within the
thyroid, the pancreas, the adrenal… polyglandular
C-peptide level undetectable in type I.
When would you see C-peptide level be high
in type II, early or late disease?
Early will be high, late undetectable or very,
very slightly detectable.
What does C-peptide mean to you?
Endogenous production of insulin.
strong family history in type II.
Other autoimmune disorders for sure in type
I and I walked you through all of these, your
patients here tend to be more of females.