Diabetes Flashcards
Describe how glucose trigger insulin secretion from pancreatic beta cells.
GLUT2 transporter glucose into cell of pancreatic beta
glucose is broken down and increases the ATP
High ATP inhibits K+ channel.
Depolarization.
Voltage-gated Ca++ channel opens, and Ca++ comes in.
Ca++ causes the release of insulin vesicles
Which tissues in the body have insulin-dependent glucose transporters? What is the effect of insulin on these?
adipose tissue
skeletal muscle
**insulin also increases the amount of GLUT4 receptors on the surface
Describe the basic symptoms of diabetes?
hyperglycemia polyuria polydipsia polyphagia (can't get glucose you do have in your cells!) weight loss (if Type I)
What is the dangerous thing to watch out for w/ Type I and Type II diabetes?
Type 1: diabetic ketoacidosis
Type II: HHS: hyperosmolar hyperglycemic state
Where are the beta cells and alpha cells located within the pancreas?
beta cells are inside. Think: insulin is inside.
alpha cells are on the periphery
delta cells are interspersed.
What is a strange thing that glucagon stimulates?
the release of insulin
T/F Insulin crosses the placenta.
False. it does not. glucose does
What are 2 weird functions of insulin?
Na+ retention in the kidneys
increased cellular uptake of K+ and amino acids (be are building things here, people!)
WHere is GLUT1 found?
brain, RBCs, cornea
Where is GLUT2 found?
pancreatic beta cells
kidney
liver
SI
Where is GLUT3 found?
brain
Where is GLUT5 found?
this is the fructose one
spermatocytes
GI tract
Which antibody is found in Type 1 diabetes?
islet cell antibody
for glutamic acid decarboxylase (GAD)
What is the genetic association w/ Type I diabetes?
HLA-DR3, HLA-DR4
What histo is seen in Type II diabetes?
islet amyloid polypeptide deposits
What are some different treatment options for neuropathic pain from diabetes?
gabapentin
pregabalin
duloxetine
amitriptyline
What are the 2 main categories of complications in diabetes?
non-enzymatic glycosylation
osmotic damage
what types of damage do you see with non-enzymatic glycosylation?
small vessel disease: retinopathy, glaucoma, neuropathy, nephropathy. leaky vessels. thickening of basement membrane
large vessel atherosclerosis contributor. Gangrene. MI.
What’s the deal with the retinopathy produced by diabetes?
nonprolif phase and then proliferative phase where you get the growth of a ton of blood vessels
leaky vessels. hemorrhage. blindness possible.
**may also see cotton wool spots (non-specific)
What types of damage do you see with osmotic damage in diabetes?
neuropathy (motor, sensory, autonomic)
cataracts
**think about sorbitol accumulation in tissue w/ aldolase reductase and without sorbitol dehyrogenase
Which tissues have aldolase reductase, but not sorbitol dehydrogenase? What is this MOA and damage?
Glucose–>Sorbitol via aldolase reductase
Sorbitol–>Fructose via sorbitol dehydrogenase
**schwann cells, lens, retina, kidney
Describe what is going on with DKA in T1DM emergencies.
insulin deficiency-determines severity
glucagon increases–>glucose increases & ketone bodies increase
**glucose leads to polyuria and dehydration
**ketone bodies are acids, leads to anion gap metabolic acidosis
get kussmaul respirations to try to compensate
no serum hyperosmolarity
Describe what is going on w/ HHS in T2DM emergencies.
no ketoacidosis
roughly normal insulin levels
this insulin inhibits lipolysis and ketone body formation
no kussmaul
extreme hyperglycemia>800
serum hyperosmolar>340!
Presenting symptoms: may be confusion, coma
What is the treatment for diabetic ketoacidosis?
ICU
IV Fluids (To fix dehydration)
Insulin drip (for the purpose of inhibiting lipolysis and ketone formation)
Monitor anion gap acidosis
Give insulin or even insulin and glucose until gap is closed
fix potassium and magnesium
What is the treatment for HHS?
IV fluids
insulin–for the purpose of decreasing serum glucose
potassium
What are some common triggers of DKA in T1DM patients?
undiagnosed diabetes-first presentation! missed insulin doses dehydration alcohol or drug abuse Severe medical illness (MI, CVA, trauma) infection (pneumonia, gastroenteritis, UTI)
What are the short-acting insulins used with meals?
aspart
glulisine
lispro
What are the long-acting 24 hour insulins?
glargine
detemir
Regular insulin is usu depleted at about ___ hours.
6 hours
NPH is a type of insulin that lasts ___ hours.
12 hours, fully gone by 18 hours
What are incretins?
made in GI
increase insulin secretion
messed up in T2DM
Ex: GLP-1
What is the MOA of DPP-4 inhibitors?
inhibit DPP-4, which inhibits GLP-1 and other incretins
What is the effect of incretin?
increase insulin
decrease glucagon
delays gastric emptying
What are the DPP-4 inhibitors?
sitagliptin
saxagliptin
alogliptin
linagliptin
What is the MOA of GLP-1 agonists?
act like an incretin
exenatide is made from a hormone found in Gila monster saliva
**increase satiety and may even cause weight loss!
What are the SE of GLP-1 agonists?
nausea
increased risk for acute pancreatitis
What are the GLP-1 agonists?
exenatide
liraglutide
albiglutide
dulaglutide
What is the MOA of SGLT-2 inhibitors?
inhibit sodium glucose linked transporter in the kidney
blocks reabsorption of glucose
**can also cause weight loss
What is the SE of SGLT-2 inhibitors?
need normal kidney
can increase risk of UTIs b/c of increased glucose down there
mycosis possible
What are the SGLT-2 inhibitors?
dapagliflozin
empagliflozin
canagliflozin
Which diabetes meds have hypoglycemia as an SE?
sulfonylureas
insulin
Which drugs are not safe in patients with fluid balance problems, such as CHF?
TZDs
Which drugs should not be used in patents with kidney dysfunction?
metformin
SGLT-2 inhibitors
sulfonylureas
Which drugs may actually help w/ weight loss?
metformin
DPP-4 inhibitors
GLP-1 agonist
SGLT-2 inhibitors
What is a useful diabetes med for patients with kidney dysfunction,b /c it is metabolized by the liver?
TZDs
Which drugs decrease hepatic gluconeogenesis?
metformin
TZDs
What is a possible non-insulin treatment for patients with organ failure?
DPP-4 inhibitors
What are possible fatal effects of DKA?
cardiac arrhythmias b/c of altered K+ & Mg
-include Vtach and torsades de point(mg)
Mucormycosis–>brain abscess if sinus infection
What are the biguanides and their MOA?
metformin
basically, decrease gluconeogenesis, increase glycolysis, increase peripheral glucose uptake and increase insulin sensitivity
**can be used if patients don’t have islet cell function
What are the SE & contraindications of metformin?
GI upset
lactic acidosis–watch for patients w/ renal insufficiency
What is the MOA of sulfonylureas? And the 2nd gen drugs?
inhibit K+ pump on pancreatic beta cells. Cause depolarization, ca++ influx and release of insulin
Glimepiride
Glipizide
Glyburide
What are the SE of the 2nd gen sulfonylureas?
hypoglycemia
weight gain
What are the 1st gen sulfonylureas and their potential side effects?
chlorpropamide
tolbutamide
disulfiram-like reaction
hypoglycemia risk
What is the MOA of TZDs? What are they?
increase insulin sensitivity by binding to PPARgamma
regulates fatty acid storage and glucose metabolism
pioglitazone
rosiglitazone
What are the SE of TZDs?
Weight gain
Edema->bad for CHF
hepatotoxicity
What is the MOA of amylin analogs?
Pramlintide
decrease gastric emptying
decrease glucagon
**amylin usu released w/ insulin
What is the MOA of the alpha glucosidase inhibitors?
Acarbose
Miglitol
intestinal brush border enzyme inhibitors
decreases carb absorption
GI disturbances!!
