Flashcards in Oral Glycemic 1 Deck (30)
What are the two primary techniques to assess glycemic control?
patient self-monitoring glucose levels
What is the difference between Type 1 and Type 2 DM?
1- autoimmune, beta cell destruction--> no insulin production
2- progressive insulin secretory defect
Outside of DMT1 and DMT2, what are some other specific types of Diabetes?
genetic defects in beta cell function/ insulin action
diseases of exocrine function
The lecture described two studies relating glycemic control to complications of DM, what was the result?
better glucose control decreases both microvascular and macrovascular complications
How do you treat Type 1 DM? Type 2?
Type 1: insulin required
Type 2: 1st diet and exercise + initiate metformin
- if they are markedly symptomatic +/- elevated blood glucose/ A1c--> consider insulin
- if noninsulin monotherapy at max dose does not reach target A1c--> add second oral agent
How does Type 2 DM develop?
alpha cells dysfunction-->secrete inappropriately high levels of glucagon + amyloid plaques + fewer beta cells --> secrete insufficient levels of insulin=> HYPERGLYCEMIA
beta cell mass decreases over time => disease progression
what are incretin hormones?
-synthesized in L cells in the ileum and colon
-secreted in response to incoming nutrients
-stimulate insulin secretion
how were incretin hormones first discovered?
insulin response to oral glucose was greater than the response to IV glucose
what is the most important incretin hormone in humans?
glucagon-like peptide 1 (GLP1)
What is the t1/2 of GLP1? Where are GLP1 receptors? How is it metabolized?
t1/2: 2-3 min
receptors in islet cells, CNS, plus more
metabolized by DPP-4
*secretion impaired by DMT2
What does GLP1 do?
-enhances glucose-dependent insulin secretion
-slows gastric emptying
-suppresses glucagon secretion
-enhances beta cell proliferation (probably only in rodents)
-may improve insulin sensitivity
What are the pathophys. mechanisms of DMT2?
decreased incretin effect
increased hepatic glucose prouction
decreased peripheral glucose uptake
increased pancreatic glucagon secretion
decreased pancreatic insulin secretion
What is the target HbA1C for diabetics?
pre-prandial plasma glucose?
post-prandial plasma glucose?
What class is metformin in?
what is the mechanism of metformin (biguanides)?
activates AMP-kinase--> decreases hepatic glucose production and intestinal glucose absorption, increases insulin action
how do sulfonylureas work? what are some of their names?
they close the K-ATP channels on beta cell plasma membranes--> increases insulin secretion
What class are Repaglinide and Nateglinide in? How do they work?
mech: same as sulfonylureas
Pioglitazone: class and MOA?
MOA: activates nuclear transcription factor PPAr-gamma--> increases peripheral insulin sensitivity
Why is Pioglitazone infrequently used?
lots of side effects: weight gain, edema, HF, bone fractures, increased risk of bladder cancer
what is the newer Thiazolidinedione that has less side effects than Pioglitazone?
what are the alpha-glucosidase inhibitors and what is their MOA?
acarbose and miglitol
MOA: inhibits intestinal alpha-glucosidase--> slows carb breakdown
**nonsystemic, must take with every meal, no as effective as metformin in reducing A1c
GLP1 Receptor agonists: names and MOA
MOA: activates GLP1 receptors--> increased insulin secretion, decreased glucagon secretion, slows gastric emptying, increased satiety
What is unique about the mode of delivery for the GLP1 receptor agonists?
they are only injectable, unlike most other non-insulin tx for DMT2
What are the DPP4 inhibitors and how do they wrk?
Sitagliptin, Vildagliptin, saxagliptin, linagliptin
moa: inhibits DPP4 activity--> increase GLP1, GIP and insulin concentration, decrease glucagon
what class is Canagliflozin? moa?
sodium glucose cotransporter 2 inhibitor = SGLT2
moa: reduces glucose resorption in the kidney--> increases urinary glucose excretion
***may cause volume depletion, genital mycotic infections, UTIs, expensive
What are the bile acid sequestrants and how do they work? when is it used?
moa: binds bile acids/ cholesterol
this is primarily used for HTN but it shows a modest reduction in A1c so it could be a good drug for diabetics with HTN
Bromocriptine is a ________ agonist. It works by______. What does it do to insulin? Side effects?
bromocriptine is a dopamine-2 agonist
it works by activating dopaminergic receptors--> alters hypothalamic regulation of metabolism and increases insulin sensitivity
* bonus: No hypoglycemia
Side effects: dizziness/ syncope, nausea, fatigue, rhinitis
Name the non-insulin tx for DMT2 that cause weight gain
Name the non-insulin tx for DMT2 that cause weight loss
GLP1 receptor agonists