04c: Diabetes Part II Flashcards
List the diabetes meds that are “insulin sensitizers”
- Biguande (Metformin)
2. Thiazolidinediones
Main mechanisms by which Metformin workds
- Increases insulin sensitivity
2. Decreases gluconeogenesis
(X) drug is first-line for essentially all patients with DM II
X = Metformin
Two main side effects of Metformin. Star the more common one
- GI (abd cramping, nausea, etc)*
2. Lactic acidosis
Contraindications for Metformin use:
- DM I
- Renal insufficiency (drug is renally cleared)
- Liver failure
- CHF
- Prior lactic acidosis on metformin
Thiazolidinediones (TZDs), such as (X), have which mechanism of action?
X = Piogiltazone
Bind PPAR-y and alpha receptors; increase glucose uptake and decrease gluconeogen
Which “insulin sensitizer” med preferred in patients with high lipid profile?
TZDs
Lower TG and increase HDL
List the diabetes meds that are “secretagogues”
- Sulfonylureas
2. Meglitinides
Primary mechanism of action of sulfonylurea
Secretagogue (increases beta cell insulin release)
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:
Don’t; you won’t improve effect, but increase risk for side effects (hypoglycemia, weight gain, drug interactions)
(X) DM II meds have black box warning on all first-gen meds since 1970. This is due to which side effect?
X = sulfonylureas (esp glyburide)
Increase CV mortality
Meglitinide mechanism of action
Secretagogue
Beta cell depolarization (by closing K-ATP channel) and insulin release
(Glipizide/meglitinide) is more useful for post-prandial hyperglycemia than for fasting glucose reduction.
Meglitinide
List the “hormone replacement” diabetes meds
- Alpha-glucosidase inhibitors
2. Amylin replacement
Alpha-glucosidase inhibitors mechanism of action
Competitively inhibit hydrolytic enzymes in gut (slows glucose absorption)
Alpha-glucosidase inhibitors side effects
Many GI issues (flatulence, diarrhea, cramping) - no longer popular in US
List the “incretin mimetics” diabetes meds
- GLP-1 R agonist
2. DPP-4 inhibitors
GLP-1 is a(n) (X) hormone released from (Y). It stimulates:
X = incretin Y = L cells (in ileum and colon)
Insulin response from beta-cells in glucose-dependent manner
GIP is a(n) (X) hormone released from (Y). It stimulates:
X = incretin Y = K cells (in duodenum)
Insulin response from beta-cells in glucose-dependent manner
(GLP1/GIP) (stimulate/inhibit) glucagon secretion from alpha cells.
GLP-1
GIP has no effect on glucagon
Exenatide, GLP-1 R agonist, differs in which ways from endogenous GLP-1?
- Resistant to DDP-4 degradation (so long duration in plasma following SC injection)
(X) is the most popular GLP-1 agonists due to its (Y) effects, independent of glucose-lowering effects.
X = Liraglutide Y = Cardiac benefits
(X) DM II meds are associated with medullary thyroid cancer.
X = GLP-1 agonists
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?
GLP-1 agonist
T/F: GLP-1 agonists are all injectible
True
DDP-4 inhibitors are (injectable/oral) meds and should be avoided in which patients?
Oral
Patients with heart failure
Black box warning on (X) DM II meds for arthralgia.
X = DDP-4 inhibitors
(X) meds for DM II work by increasing urinary glucose excretion. These work in which part of kidney?
X = SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin)
Prox tubule
Recent data shows that (X) DM II med causes 2x increase in amputations in patients with CV disease.
X = Canagliflozin (SGLT2 inhibitor)
List the human insulin preparations used for DM
Regular, NPH, U500
Insulin U500 is used for which patients?
Very Obese
It’s regular insulin, 5x concentrated
Insulin analogues are divided into which subcategories?
Long-acting (glargine, detemir, degludec)
Short-acting (aspart, glulisine, lispro)
Goal HbA1c for adult diabetic patients:
Less than 7%
Goal pre-prandial/fasting glucose level for diabetic patients:
80-130 mg/dL
Goal post-prandial glucose level for diabetic patients:
under 180 mg/dL
Why is goal HbA1c for peds diabetic patients (lower/higher) than that for adults?
Higher (7.5% or so)
Safe value since kids may not express hypoglycemia symptoms as clearly
T/F: All-cause mortality is lower in DM patients who undergo “intensive” therapy (bring glucose levels down to near-normal values).
False! Higher mortality in this group
First stage of diabetic retinopathy is called (X) and is characterized by which changes?
X = background diabetic retinopathy
- Pericyte and Endothelial cell loss (apoptosis)
- Microaneurysms
- Vascular BM thickening
(Increased/decreased) (X) growth factor levels play critical role in diabetic neuropathy. What causes these pathologic levels?
Increased
X = angiogenic -
FGF, IGF, TGFbeta,
VEGF (neovascularization)
Ischemia (impaired retinal blood flow, capillary occlusion)
Neovascularization: why are new vessels a bad thing?
Vessels are leaky (abnormal) Uncontrolled growth (grow into macula - a forbidden area with no vessels normally)
List the three key complications/changes in diabetic retinopathy
- Retinal detachment
- Uncontrolled angiogenesis
- Leaky cap’s (macular edema)
Which tools/tests can be used to inspect eye for changes in diabetic retinopathy
- Retinal angiography (inject dye, observe/take pics of retina)
- OCT scanner
Diabetic retinopathy: which tool used to assess retinal thickening?
OCT scanner
Macular edema in diabetic patient can be easily diagnosed via (X) tool
X = OCT scanner
T/F: Glaucoma is the leading cause of blindness worldwide.
False - second leading cause
Aqueous humor formation involves which 3 stages?
- Blood flows (in cap’s) to ciliary process
- Ultrafiltration (plasma into interstitium and ciliary epithelia)
- Secretion (from ciliary epithelial cells into post chamber)
Aqueous humor outflow path is to (X) compartment, passing one-way valve formed by which structures?
X = anterior chamber
Lens and iris
From (anterior/posterior) chamber, aqueous humor pass through (X), enters (Y) canal and then out into venous circulation
Ant
X = trabecular meshwork (TMW)
Y = canal of schlemm
What’s the mechanism behind (open/closed)-angle glaucoma in diabetic patients?
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
Diabetic patient presents with visual complaints. He reports spotty blank areas in visual field. This is consistent with which diabetic eye complication?
Retinopathy
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?
Glaucoma
List some meds used to treat open-angle glaucoma by decreasing aqueous humor production
Timolol, Dorzolamide
List some meds used to treat open-angle glaucoma by increasing outflow of aqueous humor
Latanoprost, pilocarpine
DM patients have (X)-fold increased risk of developing cataracts. The key mechanism behind this is excess (Y).
X = 4 Y = sorbitol (due to high glucose levels) - disrupts osmotic balance in lens
High (X) levels in DM causes lens to (swell/shrink), damaging lens fibers and forming cataract
X = sorbitol
Swell (hydropic lens)
Increased free radical formation in diabetes has been shown to cause which eye complication?
Cataracts
Diabetic patient presents with visual complaints. She feels like she’s been having “misty” vision. This is consistent with which diabetic eye complication?
Cataract
Rx of cataracts for DM
Early cataract extraction
(Duration/severity) of diabetes/hyperglycemia is key to development of ocular complications.
Both; note that severity of hyperglycemia can be controlled
