04c: Diabetes Part II

Question 1

List the diabetes meds that are “insulin sensitizers”

Answer 1

1. Biguande (Metformin)

2. Thiazolidinediones

Question 2

Main mechanisms by which Metformin workds

Answer 2

1. Increases insulin sensitivity

2. Decreases gluconeogenesis

Question 3

(X) drug is first-line for essentially all patients with DM II

Answer 3

X = Metformin

Question 4

Two main side effects of Metformin. Star the more common one

Answer 4

1. GI (abd cramping, nausea, etc)*

2. Lactic acidosis

Question 5

Contraindications for Metformin use:

Answer 5

1. DM I
2. Renal insufficiency (drug is renally cleared)
3. Liver failure
4. CHF
5. Prior lactic acidosis on metformin

Question 6

Thiazolidinediones (TZDs), such as (X), have which mechanism of action?

Answer 6

X = Piogiltazone

Bind PPAR-y and alpha receptors; increase glucose uptake and decrease gluconeogen

Question 7

Which “insulin sensitizer” med preferred in patients with high lipid profile?

Answer 7

TZDs

Lower TG and increase HDL

Question 8

List the diabetes meds that are “secretagogues”

Answer 8

1. Sulfonylureas

2. Meglitinides

Question 9

Primary mechanism of action of sulfonylurea

Answer 9

Secretagogue (increases beta cell insulin release)

Question 10

DM II: You start your patient on Glipizide and get 80% max effect at half the max dose of the drug. You (do/don’t) decide to increase the dose because:

Answer 10

Don’t; you won’t improve effect, but increase risk for side effects (hypoglycemia, weight gain, drug interactions)

Question 11

(X) DM II meds have black box warning on all first-gen meds since 1970. This is due to which side effect?

Answer 11

X = sulfonylureas (esp glyburide)

Increase CV mortality

Question 12

Meglitinide mechanism of action

Answer 12

Secretagogue

Beta cell depolarization (by closing K-ATP channel) and insulin release

Question 13

(Glipizide/meglitinide) is more useful for post-prandial hyperglycemia than for fasting glucose reduction.

Answer 13

Meglitinide

Question 14

List the “hormone replacement” diabetes meds

Answer 14

1. Alpha-glucosidase inhibitors

2. Amylin replacement

Question 15

Alpha-glucosidase inhibitors mechanism of action

Answer 15

Competitively inhibit hydrolytic enzymes in gut (slows glucose absorption)

Question 16

Alpha-glucosidase inhibitors side effects

Answer 16

Many GI issues (flatulence, diarrhea, cramping) - no longer popular in US

Question 17

List the “incretin mimetics” diabetes meds

Answer 17

1. GLP-1 R agonist

2. DPP-4 inhibitors

Question 18

GLP-1 is a(n) (X) hormone released from (Y). It stimulates:

Answer 18

X = incretin
Y = L cells (in ileum and colon)

Insulin response from beta-cells in glucose-dependent manner

Question 19

GIP is a(n) (X) hormone released from (Y). It stimulates:

Answer 19

X = incretin
Y = K cells (in duodenum)

Insulin response from beta-cells in glucose-dependent manner

Question 20

(GLP1/GIP) (stimulate/inhibit) glucagon secretion from alpha cells.

Answer 20

GLP-1

GIP has no effect on glucagon

Question 21

Exenatide, GLP-1 R agonist, differs in which ways from endogenous GLP-1?

Answer 21

1. Resistant to DDP-4 degradation (so long duration in plasma following SC injection)

Question 22

(X) is the most popular GLP-1 agonists due to its (Y) effects, independent of glucose-lowering effects.

Answer 22

X = Liraglutide
Y = Cardiac benefits

Question 23

(X) DM II meds are associated with medullary thyroid cancer.

Answer 23

X = GLP-1 agonists

Question 24

DM II patient presents with severe RUQ pain, esp after eating fatty meal. She’s diagnosed with cholelithiasis. Which DM II medication may be in her regimen, if this is a side effect of meds?

Answer 24

GLP-1 agonist

Question 25

T/F: GLP-1 agonists are all injectible

Answer 25

True

Question 26

DDP-4 inhibitors are (injectable/oral) meds and should be avoided in which patients?

Answer 26

Oral Patients with heart failure

Question 27

Black box warning on (X) DM II meds for arthralgia.

Answer 27

X = DDP-4 inhibitors

Question 28

(X) meds for DM II work by increasing urinary glucose excretion. These work in which part of kidney?

Answer 28

X = SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) Prox tubule

Question 29

Recent data shows that (X) DM II med causes 2x increase in amputations in patients with CV disease.

Answer 29

X = Canagliflozin (SGLT2 inhibitor)

Question 30

List the human insulin preparations used for DM

Answer 30

Regular, NPH, U500

Question 31

Insulin U500 is used for which patients?

Answer 31

Very Obese | It's regular insulin, 5x concentrated

Question 32

Insulin analogues are divided into which subcategories?

Answer 32

Long-acting (glargine, detemir, degludec) Short-acting (aspart, glulisine, lispro)

Question 33

Goal HbA1c for adult diabetic patients:

Answer 33

Less than 7%

Question 34

Goal pre-prandial/fasting glucose level for diabetic patients:

Answer 34

80-130 mg/dL

Question 35

Goal post-prandial glucose level for diabetic patients:

Answer 35

under 180 mg/dL

Question 36

Why is goal HbA1c for peds diabetic patients (lower/higher) than that for adults?

Answer 36

Higher (7.5% or so) Safe value since kids may not express hypoglycemia symptoms as clearly

Question 37

T/F: All-cause mortality is lower in DM patients who undergo "intensive" therapy (bring glucose levels down to near-normal values).

Answer 37

False! Higher mortality in this group

Question 38

First stage of diabetic retinopathy is called (X) and is characterized by which changes?

Answer 38

X = background diabetic retinopathy 1. Pericyte and Endothelial cell loss (apoptosis) 2. Microaneurysms 3. Vascular BM thickening

Question 39

(Increased/decreased) (X) growth factor levels play critical role in diabetic neuropathy. What causes these pathologic levels?

Answer 39

Increased X = angiogenic - FGF, IGF, TGFbeta, VEGF (neovascularization) Ischemia (impaired retinal blood flow, capillary occlusion)

Question 40

Neovascularization: why are new vessels a bad thing?

Answer 40

``` Vessels are leaky (abnormal) Uncontrolled growth (grow into macula - a forbidden area with no vessels normally) ```

Question 41

List the three key complications/changes in diabetic retinopathy

Answer 41

1. Retinal detachment 2. Uncontrolled angiogenesis 3. Leaky cap's (macular edema)

Question 42

Which tools/tests can be used to inspect eye for changes in diabetic retinopathy

Answer 42

1. Retinal angiography (inject dye, observe/take pics of retina) 2. OCT scanner

Question 43

Diabetic retinopathy: which tool used to assess retinal thickening?

Answer 43

OCT scanner

Question 44

Macular edema in diabetic patient can be easily diagnosed via (X) tool

Answer 44

X = OCT scanner

Question 45

T/F: Glaucoma is the leading cause of blindness worldwide.

Answer 45

False - second leading cause

Question 46

Aqueous humor formation involves which 3 stages?

Answer 46

1. Blood flows (in cap's) to ciliary process 2. Ultrafiltration (plasma into interstitium and ciliary epithelia) 3. Secretion (from ciliary epithelial cells into post chamber)

Question 47

Aqueous humor outflow path is to (X) compartment, passing one-way valve formed by which structures?

Answer 47

X = anterior chamber Lens and iris

Question 48

From (anterior/posterior) chamber, aqueous humor pass through (X), enters (Y) canal and then out into venous circulation

Answer 48

Ant X = trabecular meshwork (TMW) Y = canal of schlemm

Question 49

What's the mechanism behind (open/closed)-angle glaucoma in diabetic patients?

Answer 49

Open-angle (angle between iris and lens still open); High glucose-induced excess synthesis of ECM in TMW and Schlemm's canal blocks aqueous humor outflow

Question 50

Diabetic patient presents with visual complaints. He reports spotty blank areas in visual field. This is consistent with which diabetic eye complication?

Answer 50

Retinopathy

Question 51

Diabetic patient presents with visual complaints. She feels like her vision has been reduced to a small area in the center (decreased vision on all sides). This is consistent with which diabetic eye complication?

Answer 51

Glaucoma

Question 52

List some meds used to treat open-angle glaucoma by decreasing aqueous humor production

Answer 52

Timolol, Dorzolamide

Question 53

List some meds used to treat open-angle glaucoma by increasing outflow of aqueous humor

Answer 53

Latanoprost, pilocarpine

Question 54

DM patients have (X)-fold increased risk of developing cataracts. The key mechanism behind this is excess (Y).

Answer 54

``` X = 4 Y = sorbitol (due to high glucose levels) - disrupts osmotic balance in lens ```

Question 55

High (X) levels in DM causes lens to (swell/shrink), damaging lens fibers and forming cataract

Answer 55

X = sorbitol | Swell (hydropic lens)

Question 56

Increased free radical formation in diabetes has been shown to cause which eye complication?

Answer 56

Cataracts

Question 57

Diabetic patient presents with visual complaints. She feels like she's been having "misty" vision. This is consistent with which diabetic eye complication?

Answer 57

Cataract

Question 58

Rx of cataracts for DM

Answer 58

Early cataract extraction

Question 59

(Duration/severity) of diabetes/hyperglycemia is key to development of ocular complications.

Answer 59

Both; note that severity of hyperglycemia can be controlled