3.D Flashcards
What is the normal exocrine and endocrine function of the pancreas?
exocrine: secretes digestive enzymes into the GI tract
endocrine: secretes hormones from the islet of Langerhans
Which hormones are released from the islets of Langerhans?
B cells: insulin
a cells: glucagon
Describe glucose and insulin homeostasis?
homeostasis maintains a balance of large upswings and downswings of blood sugar due to eat; not a straight line
insulin release follows a similar pattern; released in response to high BG levels
When is insulin released and what is its role?
released in response to high blood sugar
promotes uptake, utilization, and storage of glucose (lowers BG concentration)
When is glucagon released and what is its role?
released in response to low blood sugar
increases the hepatic glucose output (increases BG concentration)
What can stimulate insulin release?
elevation of blood glucose
amino acids or fatty acids
GLP-1, GIP, epinephrine, adrenergic and cholinergic stimulation, estrogen
During times of stress, what can antagonize insulin?
glucagon
cortisol
growth hormone
What are the insulin sensitive tissues?
muscle
adipose
liver
brain
Which organ does not require insulin to get glucose?
brain
What is the simple way to describe insulin?
insulin is a “key” for glucose to get into cells
Describe insulin release.
- person eats food and its broken down into glucose
- glucose enters beta cells in pancreas via GLUT2 transporter
- each glucose is broken down to ATP and attaches to an ATP-
sensitive K channel and closes it - causes depolarization-amount of depolarization=amount of
Ca channels that open - Ca enters and facilitates exocytosis of insulin
How does the pancreas know how much insulin to release?
proportional amount of insulin is released is determined by the amount of glucose that enters the beta cell
Describe insulin signal transduction.
- insulin binds to the insulin receptor
- cascade of protein activations and translocation of GLUT4
- glucose enters the cell
- cells converts to whatever is needed
Differentiate between the basal and bolus release rate.
basal: constant release rate, every 3-6min
bolus: at mealtime, insulin is rapidly released in response to
food
What are the incretin hormones?
GLP-1 and GIP
-secreted by GI tract at basal level or bolus
DPP-4
-inactivates the above
True or false: there is a strong correlation between obesity and insulin resistance
true
What causes insulin resistance?
excess nutrition leads to storage of triglycerides in adipose tissue, peripherally then viscerally which causes:
-enhanced sensitivity to counter-regulatory hormones by
expressing more B receptors and activates more cortisol
-lowers insulin receptor affinity
What is diabetes mellitus?
metabolic disorder characterized by the presence of hyperglycemia due to defective insulin secretion, insulin action, or both
Differentiate between type 1 and type 2 diabetes.
type 1: due to defective insulin secretion (auto-immune)
type 2: due to insulin resistance, eventually leading to
defective insulin secretion
What is diabetes insipidus?
more of a kidney disease, deficiency of vasopressin
unrelated to pancreas
only thing in common is polyuria
What are the complications of diabetes?
macrovascular: dyslipidemia, hypertension, CAD, stroke, ED
microvascular: nephropathy, retinopathy, peripheral
neuropathy
What causes type 1 diabetes?
autoimmune destruction of pancreatic beta cells, causing lack of insulin secretion
What are the signs and symptoms of type 1 diabetes?
hyperglycemia
fatigue
polyphagia
weight loss
polyuria
glucosuria
polydipsia
What happens with severe, undiagnosed type 1 diabetes?
diabetic ketoacidosis
-ketones for energy–>keto acids–>coma–>death
What are the distinguishing side effects of diabetic ketoacidosis?
deep and laboured breathing
breath smells like acetone
What is the treatment of type 1 diabetes?
biological insulin
True or false: type 2 has more distinct phases of progression and is slower than the progression of type 1
true
What causes type 2 diabetes?
environment (overeating, sedentary lifestyle, aging)
genetic predisposition
What are the signs and symptoms of type 2 diabetes?
depends on stage of progression
can be asymptomatic at diagnosis
any type 1 signs
overweight or obese (85%)
may have developed complications
What is the treatment of type 2 diabetes?
lifestyle and healthy diet alone or in addition to oral hypoglycemic, may eventually need insulin
What is the goal of giving diabetics oral medications or insulin?
to mimic the normal production and release of insulin to accomplish glucose homeostasis
What is fasting glucose?
no caloric intake for at least 8h, used to indicate BG before a meal (pre-prandial)
mmol/L
snapshot in time
What is post-prandial glucose?
2 hours after a meal
mmol/L
snapshot in time
What is hemoglobin A1C?
an average of blood glucose control over the last 3 months
% of Hb that has been glycosylated, correlates with BG levels
Hb cell lives ~3 months, glycosylation is irreversible
What are the targets of diabetics?
A1C (%): <7.0 (<6.5 or 7.1-8.5 for some ppl)
FPG: 4.0-7.0
PPG: 5.0-10.0, 5.0-8.0 if A1C not met
What is considered to be hyperglycemia? What does it look like?
FPG>7.0mmol/L
polyuria, polydipsia, polyphagia, glucosuria, fatigue
What is considered to be hypoglycemia? What does it look like?
FPG<4.0mmol/L
mild–>moderate–>severe–>coma/death
autonomic–>neurological changes
What are the characteristics that vary with insulin treatment?
onset of action
time to peak glycemic effect
duration of action
appearance
What is the faster acting bolus insulin?
insulin aspart (Fiasp)
What are the rapid acting bolus insulin analogues?
insulin lispro (Humalog)
insulin aspart (NovoRapid)
insulin glulisine (Apidra)
What are the rapid acting insulins?
insulin, regular U100 (Humulin R & Novolin Toronto)
-bolus
insulin regular U500 (bolus and basal)
What is the intermediate acting basal insulin?
insulin, NPH (Humulin N & Novolin NPH)
What are the long acting basal insulin analogues?
insulin detemir (Levemir)
insulin glargine (Lantus)
insulin degludec (Tresiba)
Which insulin has a cloudy appearance?
insulin, NPH (Humulin N & Novolin NPH)
Describe how insulin detemir works.
after injection, self-associates and binds to albumin–>slowly released from subcutaneous tissue into blood stream, at a slow, predictable rate
Describe how insulin degludec works.
forms multihexamers following SC injection, leading to a depot–>delayed absorption from SC tissue and also binding to albumin leads to longer time profile
Describe how insulin glargine works.
an acidic product in the vial, once injected SC the acidic solution is neutralized, and forms micro-precipitates–>slow dissolve at a slow, predictable rate
What are the routes of administration for insulin?
subcutaneously-layer of fat (most common)
with an insulin pump (continuous subcutaneous)
IV (R or Toronto, emergency only)
True or false: all insulins can be mixed
false
What are the devices for insulin administration?
insulin pens (user-friendly, simple)
insulin pumps (intense management needed)
What is lipodystrophy?
abnormal distribution of fat (atrophy and hypertrophy)
repeated injections of insulin into the same tissue over and over causes the tissue to adapt
What can worsen lipodystrophy?
frequent needle re-use
What is the suggestion for insulin injection sites?
rotate injections systematically within the same anatomical region (abdomen, thigh, under arm, love handles)
-rate of absorption remain similar
-reduces chances of lipodystrophy
Rank the ordering of injection sites in speed/consistency of absorption.
abdomen>arm>thigh>buttock
What can increase insulin absorption?
exercise
heat
massage
injection into muscle
What can decrease insulin absorption?
cold
lipohypertrophy
decreased blood flow
How should insulin be stored?
stored unopened insulin in the fridge
in-use vials & cartridges may be stored at room temp for 28d
-Humalog (lispro) states not to re-refrigerate pens when in use
-insulin detemir (Levemir) stable for 42d not refrigerated
avoid freezing or direct sunlight
What are the classes of oral hypoglycaemic?
metformin
sulfonylureas
repaglinide
thiazolidinediones
acarbose
DPP4 inhibitors
GLP-1 agonists
SGLT-2 inhibitors
What is the MOA of metformin?
increases AMPK activity
-enhances insulin sensitivity to tissue
-decreases hepatic gluconeogenesis
-decreases intestinal glucose absorption
What is often the first drug prescribed in type 2 diabetes?
metformin
What are the main adverse effects of metformin?
nausea (take with food)
diarrhea (transient-titrate slowly)
lactic acidosis (rare)
What are the sulfonylureas?
glyburide
gliclazide
glimepiride
What is the MOA of sulfonylureas?
enhance insulin secretion from the pancreas
-inhibits ATP-sensitive K channels to stimulate insulin
secretion from the functioning B cells
What are the main adverse effects of sulfonylureas?
hypoglycemia (main one)
-avoid in elders
weight gain
nausea
rash
hepatotoxicity (dont take with alcohol)
What is the MOA of repaglinide?
same mechanism as sulfonylureas but works much quicker and less effectively
What is required when taking repaglinide?
repaglinide requires the presence of glucose to exert its action
must be taken before (30mins) OR with a meal
“skip a meal, skip a dose; add a meal, add a dose”
What is the main adverse effect of repaglinide?
hypoglycemia (less than sulfonylureas)
weight gain
What are the thiazolinediones?
rosiglitazone
pioglitazone
What is the MOA of thiazolinediones?
enhance insulin sensitivity at target tissues like metformin
-agonist for PPARy
-PPARy: receptor that forces insulin receptor to the surface,
combating insulin resistance
What are the main adverse effects of thiazolinediones?
edema and fluid retention
headache
weight gain
increased risk of fractures
increased risk of CV events
What is the MOA of acarbose?
inhibits a-glucosidase, which reduces the rate of absorption of carbohydrates from the GI tract
What is required when taking acarbose?
taken with meals
What are the main adverse effects of acarbose?
abdominal cramping
diarrhea
flatulence
malabsorption of vits/mins, other drugs
What do we give someone who is hypoglycemic while taking acarbose?
glucose tabs
milk
honey
What are the DPP-4 inhibitors?
linagliptin
alogliptin
sitigliptin
saxagliptin
What is the MOA of DPP-4 inhibitors?
inhibit the breakdown of incretins, increasing and prolonging their activity
instructing pancreas to release more insulin for longer
What are the adverse effects of DPP-4 inhibitors?
hypoglycemia
cough
nasopharyngitis
rash
hypersensitivity
muscle aches/joint pain
pancreatitis
What are the GLP-1 agonists?
exenatide
liraglutide
dulaglutide
semaglutide
lixisenatide
What is the MOA of GLP-1 agonists?
mimic endogenous GLP-1
results in increased satiety, reduced gastric emptying, greater insulin secretion
What are the SGLT-2 inhibitors?
dapaglifozin
empaglifozin
canaglifozin
ertugliflozin
What is the MOA of SGLT-2 inhibitors?
increases excretion of glucose in the kidney by preventing glucose reabsorption, therefore reducing blood glucose levels
What are the main adverse effects of SGLT-2 inhibitors?
diuretic effect
hypotension
polydipsia
increased rate of UTIs
MUST HAVE ADEQUATE KIDNEY FUNCTION
