Diabetes Flashcards
Why does insulin response to oral glucose exceed response to IV glucose?
- Incretin Hormones (i.e. GLP-1)
- synthesized in L cells of ileum and colon in response to incoming nutrients
- stimulate insulin secretion, suppress glucagon
What is first-line treatment along with lifestyle interventions at the time of type 2 diabetes diagnosis? Mechanism?
Metformin
–> Activates hepatic AMP-kinase; decreases hepatic glucose production (decreases overnight fasting glucose)
What are the advantages and disadvantages of Metformin therapy?
Advantages: no weight gain, no hypoglycemia; reduction in cardiovascular events and mortality; cheap
Disadvantages: GI side effects (usually transient), lactic acidosis (rare) - contraindicated in renal disease; Vit B deficiency
What are the 4 Sulfonylureas? Mechanism?
Glipizide (Glucotrol) Glyburide Glimepiride Gliclazide -->Closure of ATP-sensitive K+ channels on β-cell plasma membrane --> stimulation of insulin release
What are the advantages and disadvantages of Glyburide and those in its class?
(sulfonylureas- stimulate insulin release)
Advantages: Reduction in cardiovascular events and mortality; cheap
Disadvantages: Weight gain; hypoglycemia (since glucose-independent)
What are the 2 Meglitinide agents? Mechanism?
Repaglinide
Nateglinide
–> Closure of ATP-sensitive K+ channels on β-cell plasma membrane –> stimulation of insulin release
What are the 2 classes that stimulate insulin secretion? What is the major difference?
Sulfonylureas & Meglitinides
- -> Meglitinides are more rapid-acting with a shorter duration and taken before each meal (less risk hypoglycemia); also cost more
- ->Sulfonylureas are taken once a day
What are 2 Thiazolidinediones that activate PPAR in Diabetes management? Mechanism? Which one has an increased risk of bladder cancer and which is contraindicated in heart disease?
Pioglitazone - (bladder cancer)
Rosiglitazone - (heart disease)
–>Binds PPAR-γ, a nuclear transcription factor; increases peripheral insulin sensitivity
What are 2 α-glucosidase inhibitors? Mechanism? What is the main side effect?
Acarbose
Miglitol
–> Taken with each meal to competitively inhibit break down of carbohydrates into simple sugars, delaying GI carbohydrate absorption & reducing postprandial glucose levels
-SE: GI- gas, flatulence, diarrhea (more popular in elderly)
What are 2 Diabetic agent classes that increase incretin effects? Mechanism and effect?
GLP-1 agonists (incretin memetics)
DPP-4 inhibitors (prevents degradation of GLP-1)
-Increase insulin secretion
-decrease glucagon secretion
What are the 2 incretin mimetics? Advantages and Disadvantages?
(GLP-1 agonists)
Exenatide
Liraglutide
-Advantages: Leads to weight reduction (increases satiety, slows gastric emptying) ; may improve β-cell mass
-Disadvantages: Acute pancreatitis; GI (nausea, vomiting, diarrhea); expensive & injection only
What are the 4 DPP-4 inhibitors? Advantages, Disadvantages?
Sitagliptin
Vildagliptin
Saxagliptin
Linagliptin
-Advantages: No hypoglycemia, weight neutrality
-Disadvantages: Urticaria/angioedema; pancreatitis; expensive
What Diabetic agent reduces glucose reabsorption in the kidney? Advantages and Disadvantages?
Canagliflozin (SGLT2 inhibitor)
- Advantages: No hypoglycemia; weight loss possible
- Disadvantages: UTIs; genital mycotic infections; volume depletion; hyperkalemia; hypersensitivity
Which agent may be given if patient is diabetic and also hyperlipidemic? Mechanism? Advantages and Disadvantages?
Colesevelam (Bile acid sequestrant)
- Advantages: No hypoglycemia; decreased LDL cholesterol
- Disadvantages: Increase in triglycerides; constipation; may interfere with absorption of other medications
What is a diabetic agent that is rarely used and works by altering hypothalamic regulation of metabolism increasing insulin sensitivity?
Bromocriptine (Dopamine-2 agonist)
Which diabetic agent is injected in combination with short or rapid-acting insulin before each meal? Mechanism? What’s a significant risk? SE?
Pramlintide (amylin analog)
- -> Mimics amylin: slows gastric emptying, suppresses postprandial glucose secretion, may reduce appetite
- hypoglycemia is significant risk
- SE: GI side effects (especially nausea)
What are the least expensive insulin agents available that are often used together? Disadvantages?
Regular - short-acting
NPH - intermediate acting
-Regular 3x (bfast, lunch, dinner) and NPH 1x at bedtime
or
-Regular 2x (bfast, dinner) and NPH 2x (bfast, dinner)
[greater likelihood of nocturnal hypoglycemia or fasting hyperglycemia]
What are 3 rapid-acting insulin agents? Onset, peak and duration times?
Lispro
Aspart
Glulisine
OoA: 5-30 min; PA: 0.5-3 hrs; DoA: 3-5 hrs
What is the onset, peak and duration times of regular insulin?
(short-acting)
OoA: 30-60 min; PA: 1-5 hrs; DoA: 6-8 hrs
What are 4 intermediate-acting insulin agents? Onset, peak and duration times?
NPH; NPL; NPA
OoA: 1-4 hrs; PA: 4-10 hrs; DoA: 14-24 hrs
Detemir (duration is dose-dependent)
OoA: 3-4 hrs; PA: 4-8 hrs; DoA: 6-24 hrs
What are 2 agents that can be used as basal insulin? What is important about these agents?
Detemir (at high doses DoA can reach 24hrs)
Glargine (OoA: 2-3 hrs; PA: none; DoA: 24-30 hrs)
–should not be mixed with other insulin preparations
What is the most common insulin agent concentration? What concentration is used for severe insulin resistance?
Most common- U-100 (100 units insulin/ml)
Severe insulin resistance- U-500
What is the only insulin agent that may be used to treat diabetic ketoacidosis?
Regular Insulin
- only agent that can be given IV
- plasma half-life <9min
Premixed Insulins are rarely used in type 1 diabetes- what are the disadvantages of premixed agents?
- loss of flexibility matching carbohydrate intake and physical activity
- harder to treat short-term high or low blood glucose
- hypoglycemia risk
What is the treatment for hypoglycemia in the hospital setting? and in the home setting?
In both cases, if patient is able they should ingest glucose (pill or food)
If patient in hypoglycemic coma:
-Hospital: IV dextrose
-Home: glucagon injection by caregiver
What are some side effects of Aspart and those in its class?
(insulin agents)
- hypoglycemia
- weight gain (glycosuria reduced, fuel-storage mechanisms restored, overeat due to fear of hypoglycemia)
- lipoatrophy (at site of injection; uncommon)
- lipohypertrophy (need to rotate site of injection to prevent)
What is the only type of insulin used in pump therapy?
rapid-acting:
insulin delivered every few minutes in small amounts with bolus doses for meals
(lispro, aspart, glulisine)
What is continuous glucose monitoring?
SQ electrochemical sensor measures interstitial glucose and sends information to transmitter and pump every 5 minutes where data can be viewed and acted on in real-time; alarms when low/high
