diabetes Flashcards
what happens to the islets in T2D?
alpha cells secrete an abnormally high amount of glucagon, there are fewer beta cells as the mass declines over time. they secrete insufficient levels of insulin over time.
what is marker of T2D after meals?q
there is a blunted insulin response and an overzealous glucagon release.
what are incretins?
synthesized in L cells in the ileum and colon. they are produced in response to incoming nutrients and stimulate insulin secretion.
what is the most important incretin?
glucagon-like peptide 1
what are the actions of GLP-1
enhances glucose dependent insulin secretion. slaws gastric emptying. suppresses glucagon secretion. promotes satiety. receptors are found on islet cells and CNS.
what happens to uncertain secretion during T2D?
it is reduced.
when to treat T2D with metformin?
at the time of diagnosis.
when to treat T2D with insulin?
patients with marked symptoms or elevated blood glucose or A1c levels.
what class is metformin?
biguanide
metformin mechanism?
activates AMP-kinase and inhibits mito isoform of glycerophosphate dehydrogenase. decreases hepatic glucose production
what are the advantages of metformin?
low cost, no weight gain, no hypoglycemia, reduction in cardiovascular and mortality risks.
what class for glibenclamide/glyburide, glipizide, gliclazide, glimepiride
sulfonylurea
mechanism for the sulfonylureas
closes the KATP channel on beta cell membranes. and increases insulin secretion.
side effects for metformin
GI side effects, lactic acidosis, b12 deficiency, contraindicated with renal malfunction.
disadvantages of sulfonylurea
there is hypoglycemia risk, weight gain, may blunt myocardial ischemic preconditioning.
class for repaglinide and nateglinide
meglitinides
mechanism for the meglitinides
closes KATP channels on the beta cell membranes. and increases insulin secretion
disadvantages of the meglitinides
there is hypoglycemia risk, weight gain, may blunt myocardial ischemic preconditioning.
class for pioglitazone
thiazolidinediones
mechanism for pioglitazone
activates the nuclear transcription factor PPAR-gamma. to increase the peripheral insulin sensitivity
advantages of pioglitazone
no hypoglycemia. increases HDL, decreases triglycerides, reduction in MI
disadvantages of pioglitazone
weight gain, edema, HF, bone fractures, increased bladder cancer.
class for rosiglitazone
thiazolidinediones
mechanism for rosiglitazone
activates the nuclear transcription factor PPAR-gamma. to increase the peripheral insulin sensitivity
advantages to rosiglitazone
no hypoglycemia
disadvantages to rosiglitazone
increases in LDL, weight gain, edema, HF, none fractures, cardiovascular events, no CHF patients
class for acarbose and miglitol
glucosidase inhibitors.
mechanism for acarbose and miglitol
inhibits the intestinal glucosidase and slows intestinal carbohydrate metabolism
advantages of acarbose and miglitol
not systemic, decreases the rise in postprandial glucose. weight neutral. no hypoglycemia
disadvantages of acarbose and miglitol
GI, dosing frquency, only modest reduction in the A1c
class for exenatide, liraglutide, albiglutide, dulaglutide.
GLP-1 receptor angonists. activates the incretin receptors.
mechanism for the GLP-1 agonists
activates the receptor, increases insulin, decreases glucagon, slows gastric emptying increases satiety.
advantages of the GLP-1 agonists
weight reduction and potential for the beat-cell mass regeneration.
disadvantages of the GLP-1 agonists
GI, pancreatitis, hypoglycemia, caution in RD, C-cell hyperplasia and medullary thyroid tumors. has to be injected.
what is the class for sitagliptin, alogliptin, saxaliptin, linagliptin
DPP-4 inhibitors, incretin enhancer
mechanism of sitagliptin, alogliptin, saxaliptin, linagliptin
inhibit DPP-4 activity, increases the active GLP1, active GIP, insulin secretion, decreases glucagon.
advantages for sitagliptin, alogliptin, saxaliptin, linagliptin
no hypoglycemia, weight neutral.
disadvantagres for sitagliptin, alogliptin, saxaliptin, linagliptin
urticaria and angioedema, pancreatitis, long term unknown
class for the “flozins”
SGLT2 inhibitors. they reduce the reabsorption in the kidney.
advantages to the flozins
weight loss, and no hypoglycemia
disadvantages of the flozins
hypokalemia, volume depletion, mycotic infections (UTI), HSR, increased LDL, long term unknown.
colesevelem class
bile acid sequester ants. these decrease hepatic glucose production
when is hypoglycemia a problem?
more common with sulfonylurea and insulin therapy. more common in T1D. increased risk if over 60, impaired renal function, poor nutrition, liver disease, increased activity, longer duration DM.
symptoms of hypglycemia
confusion, slurred speech, dizziness, weakness, shaking, palpitations, nervousness, sweating, extreme hunger, HA, mood or behavior swings, tingling of hands tongue or lips, vision changes, poor coordination, unresponsiveness, unconsciousness, or seizures.
what are the treatment recommendations for hypoglycemia
glucose! IF THEY ARE CONSCIOUS. people at high risk for hypo should be given glucagon prescription.
when is the glucagon emergency kit given
when the patient is unconscious or unable to swallow.
who should always have a script for glucagon?
T1D and severe low blood sugar in T2D.
what do we give in the hospital for severe hypoglycemia
IV dextrose
amylin
peptide released with insulin from beta cells in response to eating. absent in T1D, variable in T2D. slows gastric emptying, suppresses postprandial glucagon secretion, may reduce appetite.
pramlitide
synthetic amylin. inject before meals. for use with insulin. may give weight loss. significant risk for hypoglycemia. GI SE. especially nausea.
when is insulin indicated for T2D
glucose toxicity, insufficient endogenous production. contraindication for oral therapy. significant hyperglycemia at presentation. maximum dose of oral agents. surgery, pregnancy, decompensation, serious renal or hepatic disease.
rapid acting insulin analogs
lispro insulin, aspart, glulisine,
intermediate acting insulin analogs
determir insulin, neutral protamine lispro, neutral protamine aspart.
insulin determir characteristics
duration of action dose dependent. lower doses are intermediate acting, higher doses last 24hr. once or twice daily, delayed release from subcut injection site.
glargine insulin
long acting, is a basal formulation.
insulin storage
refrigeration is best. can be stable at RT for up to one month. never freeze and avoid sunlight.
what is lipohypertrophy
atrophy of the subcutaneous fat at the injection site.
