Oral Glycemic 1

Question 1

What are the two primary techniques to assess glycemic control?

Answer 1

patient self-monitoring glucose levels

Hemoglobin A1C

Question 2

What is the difference between Type 1 and Type 2 DM?

Answer 2

1- autoimmune, beta cell destruction–> no insulin production
2- progressive insulin secretory defect

Question 3

Outside of DMT1 and DMT2, what are some other specific types of Diabetes?

Answer 3

Gestational diabetes
genetic defects in beta cell function/ insulin action
diseases of exocrine function
drug/chemical induced

Question 4

The lecture described two studies relating glycemic control to complications of DM, what was the result?

Answer 4

better glucose control decreases both microvascular and macrovascular complications

Question 5

How do you treat Type 1 DM? Type 2?

Answer 5

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

Question 6

How does Type 2 DM develop?

Answer 6

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

Question 7

what are incretin hormones?

Answer 7

• synthesized in L cells in the ileum and colon
• secreted in response to incoming nutrients
• stimulate insulin secretion

Question 8

how were incretin hormones first discovered?

Answer 8

insulin response to oral glucose was greater than the response to IV glucose

Question 9

what is the most important incretin hormone in humans?

Answer 9

glucagon-like peptide 1 (GLP1)

Question 10

What is the t1/2 of GLP1? Where are GLP1 receptors? How is it metabolized?

Answer 10

t1/2: 2-3 min
receptors in islet cells, CNS, plus more
metabolized by DPP-4
*secretion impaired by DMT2

Question 11

What does GLP1 do?

Answer 11

• enhances glucose-dependent insulin secretion
• slows gastric emptying
• suppresses glucagon secretion
• promotes satiety
• enhances beta cell proliferation (probably only in rodents)
• may improve insulin sensitivity

Question 12

What are the pathophys. mechanisms of DMT2?

Answer 12

decreased incretin effect
increased hepatic glucose prouction
decreased peripheral glucose uptake
increased pancreatic glucagon secretion
decreased pancreatic insulin secretion

Question 13

What is the target HbA1C for diabetics?
pre-prandial plasma glucose?
post-prandial plasma glucose?

Answer 13

<180

Question 14

What class is metformin in?

Answer 14

biguanides

Question 15

what is the mechanism of metformin (biguanides)?

Answer 15

activates AMP-kinase–> decreases hepatic glucose production and intestinal glucose absorption, increases insulin action

Question 16

how do sulfonylureas work? what are some of their names?

Answer 16

they close the K-ATP channels on beta cell plasma membranes--> increases insulin secretion 
Glibenclamide/Glyburide
Glipizide
Gliclazide
Glimepiride

Question 17

What class are Repaglinide and Nateglinide in? How do they work?

Answer 17

class: meglitinides
mech: same as sulfonylureas

Question 18

Pioglitazone: class and MOA?

Answer 18

class: Thiazolidinediones
MOA: activates nuclear transcription factor PPAr-gamma–> increases peripheral insulin sensitivity

Question 19

Why is Pioglitazone infrequently used?

Answer 19

lots of side effects: weight gain, edema, HF, bone fractures, increased risk of bladder cancer

Question 20

what is the newer Thiazolidinedione that has less side effects than Pioglitazone?

Answer 20

Rosiglitazone

Question 21

what are the alpha-glucosidase inhibitors and what is their MOA?

Answer 21

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

Question 22

GLP1 Receptor agonists: names and MOA

Answer 22

Exenatide, liraglutide
MOA: activates GLP1 receptors–> increased insulin secretion, decreased glucagon secretion, slows gastric emptying, increased satiety

Question 23

What is unique about the mode of delivery for the GLP1 receptor agonists?

Answer 23

they are only injectable, unlike most other non-insulin tx for DMT2

Question 24

What are the DPP4 inhibitors and how do they wrk?

Answer 24

Sitagliptin, Vildagliptin, saxagliptin, linagliptin

moa: inhibits DPP4 activity–> increase GLP1, GIP and insulin concentration, decrease glucagon
* *expensive

Question 25

what class is Canagliflozin? moa?

Answer 25

sodium glucose cotransporter 2 inhibitor = SGLT2

moa: reduces glucose resorption in the kidney–> increases urinary glucose excretion
* *no hypoglycemia
* **may cause volume depletion, genital mycotic infections, UTIs, expensive

Question 26

What are the bile acid sequestrants and how do they work? when is it used?

Answer 26

Colesevelam
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

Question 27

Bromocriptine is a ________ agonist. It works by______. What does it do to insulin? Side effects?

Answer 27

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

Question 28

Name the non-insulin tx for DMT2 that cause weight gain

Answer 28

sulfonylureas
meglitinides
thiazolidinediones

Question 29

Name the non-insulin tx for DMT2 that cause weight loss

Answer 29

GLP1 receptor agonists

SGLT2

Question 30

What two classes of non-insulin tx for DMT2 are both cheap and work well when used together?

Answer 30

Biguanides (metformin) and sulfonylureas (glibenclamide, Glipizide, Gliclazide, Glimepiride)