Type 1 Diabetes

Question 1

Where does insulin secreted by the pancreas mostly go?

Answer 1

To the liver via the portal vein.

Question 2

4 important cell types in the islets of Langerhans?

Answer 2

beta cells - insulin
alpha cells - glucagon
delta cells - somatastatin (supresses both insulin and glucagon)
pancreatic polypeptide cells - unknown function

Question 3

In what form is insulin synthesize in beta cells? How is it released?

Answer 3

Starts as pre-proinsulin.
Cleaved in ER to proinsulin.
Proinsulin cleaved to insulin + C peptide.
Insulin + C peptide are released from secretory vesicles.

Question 4

4 necessary conditions for proper insulin function?

Answer 4

Beta cells must be there. <- problem in T1D
Beta cells must make insulin.
Beta cells must secrete insulin in response to glucose.
Insulin signaling in target cell must function.

Question 5

Other molecule missing in T1D that may be useful to administer?

Answer 5

IAPP aka amylin.

Question 6

How is endogenous insulin measured?

Answer 6

By measuring levels of C-peptide, not insulin itself.

allows you to monitor while giving exogenous insulin

Question 7

3 different ways to stimulate insulin secretion?

Answer 7

Nutrient load - mainly glucose.
Autonomic - seeing/smelling food -> vagal stimulation. (also fight-or-flight turns it off).
Hormonal - incretins (GLP-1 and GIP)

Question 8

2 ways to inhibit insulin secretion?

Answer 8

Starvation/hypoglycemia.

Hormonal - glucagon, epinephrine, growth hormone, cortisol.

Question 9

2 types of T1D?

Answer 9

Autoimmune (most common)

Non-autoimmune

Question 10

Other, less common forms of diabetes mellitus? (aside from T1D, T2D, and gestationaL)

Answer 10

LADA - latent autoimmune diabetes of adulthood.
Monogenic diabetes (beta cells don't work properly)
Secondary to other conditions (drugs, endocrinopathies, infections, etc.)
Pancreatic disease.

Question 11

3 major things that distinguish T1D from T2D?

Answer 11

There’s no insulin at all.
Way easier to get diabetic ketoacidosis (DKA).
Auto-antibodies.

Question 12

Do beta cells die in T2D?

Answer 12

Yes, but only late in the disease process.

Question 13

Boards question: You see a women with recurrent yeast infections…

Answer 13

Rule out diabetes.

Question 14

Why does glucose get into the urine?

Answer 14

Transporters for reabsorption are overwhelmed.

Question 15

Prevalence of T1D in US people under 20?

Geographic bias?

Answer 15

0.25%

More common in North American and northern European areas.

Question 16

Risk factors for T1D?

Answer 16

Lots of stuff:
Viral infections, immunizations (small effect… but really?), diet (cow’s milk?), high SES, obesity, Vitamin D deficiency… etc.

Question 17

4 auto-antibodies found in T1D? How sensitive / specific are these for T1D, roughly?

Answer 17

Islet-cell antibodies (ICA).
Insulin autoantibodies (IAA).
Antibodies to glutamic acid decarboxylase (GAD).
ZnT8…
(others exist)
These tend to be highly specific, but less sensitive. (people without T1D don’t have them, but some people have T1D and don’t have them)

Question 18

What process could trigger autoimmunity in T1D?

Answer 18

Some environmental factor that causes antigen release from beta cells.

Question 19

What can you see on histology of the pancreas in T1D?

Answer 19

Cellular infiltrate of macrophages and lymphocytes, destroying beta cells.
(high rates of co-morbidity with other autoimmune diseases)

Question 20

What’s a typical presentation of LADA?

Answer 20

Something that looks like T2D in a lean adult (>25 years), but doesn’t respond to oral glucose-lowering meds.
Antibodies found, C-peptide’s low.

Question 21

What does a basal-bolus insulin regimen try to do?

Answer 21

Mimic nature. (more on this in the insulin lecture)

Question 22

Does intensive therapy help prevent the negative sequelae of T1D?

Answer 22

Yes.

Question 23

3 effects of missing insulin in DKA, each on a specific tisse?

Answer 23

Liver: glucose production not suppressed -> high glucose -> drawing water into serum -> polyuria -> DEHYDRATION.
Muscle: lack of glucose uptake and anabolism -> WEIGHT LOSS.
Adipose: ketone production -> ACIDOSIS.

Question 24

7 signs of DKA?

Answer 24

Tachycardia (probs due to dehydration)
Hypotension (probs due to dehydration)
Dehydration
Hyperventilation (acidosis)
Weight loss
Fruit odor (ketosis)
Altered mental status

Question 25

6 symptoms of DKA?

Answer 25

Nausea/vomiting.
Thirst/polyuria
Weakness/anorexia
Abdominal pain
Visual disturbances
Somnolence.

Question 26

2 urgent problems in DKA?

Answer 26

Hyperosmolar (too much sugar) dehydration.

Acidosis

Question 27

2 adverse events of DKA treatment?

Answer 27

Cerebral edema

Hypokalemia

Question 28

Treatment of DKA?

Answer 28

Insulin!

Correct fluid and electrolyte balance (esp. K+).

Question 29

From CPC: What’s weird about measuring K+ levels in ketoacidosis?

Answer 29

K+ actually looks high because cells are exchanging H+ for K+, but really K+ overall is low and needs to be given.
(This will make more sense after renal. Hopefully.)