Now, we’ll talk about the pathogenesis, this is the most important.
It's called non-enzymatic glycosylation. 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 membrane.
When it does so, it will cause arteriosclerosis.
If it's in the capillary, it will then cause non-enzymatic glycosylation
and therefore compromise proper exchange of nutrients.
Altered carbohydrate metabolism and a second pathogenesis here is that you wanna know about sorbitol
and that’s because with all that glucose, instead of going to the glycolytic pathway,
it might end up going through what's known as aldose reductase.
With that aldose reductase in sorbitol specifically in the lens,
remember what I told you if you started with a patient with diabetes over a long period of time,
what color could their lens be?
In Greek, cataract means waterfall.
When you take a look at the waterfall, what color is that water when it's falling over the cliff?
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 into the lens,
in other words, increase osmotic pressure.
Unregulated glucose intake by this tissues partially explains why these are the main diabetes mellitus targets.
The increase glucose metabolized by the enzyme aldose reductase to sorbitol,
that’s an important point, make sure that you pay attention to that enzyme.
Two major pathogeneses that I just walked you through, the most important will be non-enzymatic glycosilation, neg,
or you might have heard of AGE, advanced glycosilated end-product - one and the same.
Capillary membrane destruction, remember the arteriosclerosis
that you found with diabetes that’s called hyaline atherosclerosis
and do not forget about the sorbitol pathogenesis.
Quickly type 1 versus type 2, a brief beautiful summary of the things that you would look at in your head now,
you should have a firm understanding as to why these things are taking place.
Type 1, weight please - normal or thin, type 2, overweight.
First step of management, type 2 diabetic lose the weight.
Age: Type 1, 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 wanna keep in mind called unconventional or MODY
in which it’s called Maturity onset of Diabetes in the young,
in which I told you to focus upon a deficiency in glucokinase gene.
If its type 2, a little bit older, 30, obese, insulin resistance.
Type 1, with glycemic pattern all over the place because of insulin pump, type 2, less variable.
Insulin sensitivity in type 1, perfectly normal hence the insulin pump.
In type 2, if the receptors aren't working how in the world is insulin even being properly responded to?
Insulin sensitivity reduced in type 2.
What about oral agents? Only effective in type 2.
Antibiotic status. In type 1 remember the topic insulitis?
I told you about your glutamic acid decarboxylase, a type 2 hypersensitivity that’s auto immunity.
So antibiotic status positive in type 1, negative in type 2.
Remember the autoimmune disease within the thyroid, the pancreas, and the adrenal, polyglandular endocrinopathy.
C-peptide level, undetectable in type 1.
When would you see C-peptide level be high in type 2?
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.
Family history - strong family history in type 2.
Other autoimmune disorders for sure in type 1 and I’ll walk you through all of these,
your patients here tend to be more of females.