Flashcards in Type 1 Diabetes Deck (29)
Where does insulin secreted by the pancreas mostly go?
To the liver via the portal vein.
4 important cell types in the islets of Langerhans?
beta cells - insulin
alpha cells - glucagon
delta cells - somatastatin (supresses both insulin and glucagon)
pancreatic polypeptide cells - unknown function
In what form is insulin synthesize in beta cells? How is it released?
Starts as pre-proinsulin.
Cleaved in ER to proinsulin.
Proinsulin cleaved to insulin + C peptide.
Insulin + C peptide are released from secretory vesicles.
4 necessary conditions for proper insulin function?
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.
Other molecule missing in T1D that may be useful to administer?
IAPP aka amylin.
How is endogenous insulin measured?
By measuring levels of C-peptide, not insulin itself.
(allows you to monitor while giving exogenous insulin)
3 different ways to stimulate insulin secretion?
Nutrient load - mainly glucose.
Autonomic - seeing/smelling food -> vagal stimulation. (also fight-or-flight turns it off).
Hormonal - incretins (GLP-1 and GIP)
2 ways to inhibit insulin secretion?
Hormonal - glucagon, epinephrine, growth hormone, cortisol.
2 types of T1D?
Autoimmune (most common)
Other, less common forms of diabetes mellitus? (aside from T1D, T2D, and gestationaL)
LADA - latent autoimmune diabetes of adulthood.
Monogenic diabetes (beta cells don't work properly)
Secondary to other conditions (drugs, endocrinopathies, infections, etc.)
3 major things that distinguish T1D from T2D?
There's no insulin at all.
Way easier to get diabetic ketoacidosis (DKA).
Do beta cells die in T2D?
Yes, but only late in the disease process.
Boards question: You see a women with recurrent yeast infections...
Rule out diabetes.
Why does glucose get into the urine?
Transporters for reabsorption are overwhelmed.
Prevalence of T1D in US people under 20?
More common in North American and northern European areas.
Risk factors for T1D?
Lots of stuff:
Viral infections, immunizations (small effect... but really?), diet (cow's milk?), high SES, obesity, Vitamin D deficiency... etc.
4 auto-antibodies found in T1D? How sensitive / specific are these for T1D, roughly?
Islet-cell antibodies (ICA).
Insulin autoantibodies (IAA).
Antibodies to glutamic acid decarboxylase (GAD).
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)
What process could trigger autoimmunity in T1D?
Some environmental factor that causes antigen release from beta cells.
What can you see on histology of the pancreas in T1D?
Cellular infiltrate of macrophages and lymphocytes, destroying beta cells.
(high rates of co-morbidity with other autoimmune diseases)
What's a typical presentation of LADA?
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.
What does a basal-bolus insulin regimen try to do?
Mimic nature. (more on this in the insulin lecture)
Does intensive therapy help prevent the negative sequelae of T1D?
3 effects of missing insulin in DKA, each on a specific tisse?
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.
7 signs of DKA?
Tachycardia (probs due to dehydration)
Hypotension (probs due to dehydration)
Fruit odor (ketosis)
Altered mental status
6 symptoms of DKA?
2 urgent problems in DKA?
Hyperosmolar (too much sugar) dehydration.
2 adverse events of DKA treatment?
Treatment of DKA?
Correct fluid and electrolyte balance (esp. K+).