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
