DM Injectable Meds

Question 1

Function of Amylin

Answer 1

• secreted by the beta cells of the pancreas
• suppresses postmeal glucagon secretion
• regulates rate of gastric emptying from stomach to small intestine
• regulates plasma glucose concentration

Question 2

Function of Glucagon

Answer 2

• secreted by alpha cells of the pancreas
• break down glycogen in the liver and muscles
• increases the glucose levels in the blood

Question 3

Types of Injectable Antiglycemics

Answer 3

1. Insulin
2. GLP-1 Agonists (Glucagon -like peptide 1)
3. Amylin Mimetics

Question 4

Rapid Acting Insulin Injectable Analogs

Answer 4

• Meds:
  
  • Glulisine (Apidra)
    
    • glutamic acid substitution
  • Aspart (Novolog, Fiasp)
    
    • Aspartic acid substitution
  • Lispro
    
    • Lysine before proline, instead of other was around
• Comments:
  
  • monotherapy or combo with oral agents
  • flexible dosing, rapid onset
  • safe in pregnancy, renal failure, liver dysfxn
  • Drug of Choice for high glycemic resistance
• SEs;
  
  • hypoglycemia, weight gain, lipodystrophy, local skin rxn

Question 5

Regular Human Insulin Properties

Answer 5

• After SQ injection:
  
  • the insulin gets diluted with the interstitial fluid → hexamers (with zinc ions in the middle) break down into dimers → then become monomers (which are biologically active
  • This is the rate limiting step in absorption
• Disadvantages:
  
  • hexamers are too big to cross the vascular endothelium
  • effects are delayed (30-60min lag time)
    
    • hypoglycemia is delayed
  • onset is slow
  • clearance is slow

Question 6

When to Use Insulin?

Answer 6

• preferred tx when A1C > 9%
• Pt does not have an adequate response to oral antiglycemics:
  
  • if A1C > 8.5% → multi-dose insulin regimen
  • if A1C ≤ 8.5% → once-daily insulin regimen preferred
• Factors to Consider:
  
  • current glycemic control
  • need for fasting and/or postprandial coverage
  • lifestyle requirements
  • liver or kidneys diseases
  • other oral antiglycemics

Question 7

Estimating Basal and Pre-Meal Insulin Requirements

Answer 7

• Estimating Basal Insulin:
  
  • ~50% of total daily daily insulin dose (TDD)
  • conservative approach: reduce the calculated 50% dose by 20% to avoid hypoglycemia
    
    • ex: TDD =25 units → 50% basal = 12.5 units → 20% reduction = 10 units basal
• Estimating pre-meal insulin:
  
  • ~50% TDD → divided into 3 doses (i.e. breakfast, lunch, dinner)

Question 8

Estimating insulin: carb ratio

Answer 8

• Rapid Acting Insulin Analog
  
  • “500 rule” → 500/TDD = grams of carb: 1 unit of insulin
    
    • pt requireds 50 units/day of rapid acting insulin → 500/50 = 10gm of carbs: 1 unit of rapid-acting insulin
• Regular Insulin:
  
  • “450 rule” → 450/TDD

Question 9

Determine the Correction Factor for Insulin Dosage

Answer 9

• Determine how far the BG drops per unit of insulin given:
  
  • Rapid-Acting insulin → use “1700 rule” or “2100 rule”
    
    • ex: pt needs 28 units/d of insulin (TDD) → 1700/28 = 60 mg/dL drop in BG for every 1 unit of rapid acting insulin
    • Regular insulin → use “1500 rule”
      
      • ex: 1500/28 = 54 mg/dL drop in BG for every 1 unit of “regular insulin”

Question 10

What causes Fasting Hyperglycemia (i.e. Morning hyperglycemia)?

Answer 10

• insufficient basal dose of insulin
  
  • i.e. hepatic glucose output is too high
• insufficient dinner coverage
  
  • i.e. not enough short acting insulin was given
• reactive hyperglycemia
  
  • usually in response to a nocturnal hypoglycemic episode
  • somogyi effect or rebound hyperglycemia rare & more often associated with DM type I
• too many late night snacks

Question 11

Somogyi Effect or Rebound Hyperglycemia

Answer 11

rare & more often associated with DM type I

• hypoglycemia in the middle of the night → increase counter-regulatory hormones (glucagon, epi, cortisol, & growth hormones) → hyperglycemia in the AM
• Hyperglycemia is atypical in AM with treatment resistance even when insulin dose was increased

Question 12

Dawn Phenomenon

Answer 12

• Rise of BG occurs between 4-8am after a physiological low point of BG level (not hypoglycemic state) occurs between 12-3am.
  
  • secondary to rising of growth hormones, cortisol, glucagon, or epinephrine
    
    • 30-40 mg/dL increase
• Tx:
  
  • increase basal insulin (i.e. insulin glargine) would be indicated
  • if hypoglycemia occurs 4-8 hrs post dose → change basal insulin to BID dosing

Question 13

GLP-1 Receptor Agonists: MOA & SEs

Answer 13

Incretin Mimetic

monotherapy: A1C reduced by 0.8-0.9%; combined therapy with others PO: A1C reduced by 1%

• What do these do:
  
  • stimulate insulin secretion
  • delays GI emptying
  • reduces postprandial glucagon level
  • improves satiety
• SEs:
  
  • GI: N/V/D
  • hypoglycemia, pancreatitis
  • weight loss
  • do not use in gastroparesis or severe GI disease or severe renal dz
  • BBW: potential risk for medullary thyroid carcinoma (MTC) & thyroid tumor sxs
    
    • for Semaglutide
• Ending in either “senatide or zenatide”:
  
  • these are derived from lizards
    
    • so more side effects/adverse rxn can be seen
• “glutide” endings:
  
  • are not derived from a lizard
    
    • so less adverse effects with these

Question 14

GLP-1 Receptor Agonist Meds

Answer 14

• Exenatide (Byetta)
  
  • (Bydureon) → from gila monster or heloderma lizard venom
• Liraglutide (victoza)
  
  • if Renal impairment = NO adjustment
• Dulaglutide
  
  • if Renal or hepatic dysfunction = no adjustment
  • SEs: N/V/D, abd pain, tachycardia av block, PR prolongation
  • causes thyroid C-cell tumors in rats
• Lixisenatide (adlyxin)
• Lixisenatide/Insulin Glargine (Soliqua)
  
  • eGFR = 15-30 ml/min – CAUTION
• Semaglutide (Ozempic)
  
  • BBW: potential risk for medullary thyroid carcinoma (MTC) & thyroid tumor sxs

Question 15

Amylin Receptor Agonist

Answer 15

• Pramlintide (Symlin or Symlinpen)
• MOA:
  
  • effects same as GLP-1 receptor agonist
  • stimulates insulin secretion
  • delays GI emptying
  • reduces glucagon level
• When to use:
  
  • use immediately before meals
  • use in combo with insulin or other PO antihyperglycemics
  • do not use in gastroparesis
• SE:
  
  • nausea, decreased appetite
  • HA, hypoglycemia
  • weight loss (mild)

Question 16

Precipitating Factors for DKA

Answer 16

• infx
• omission/inadequate insulin
• MI/stroke/trauma
• meds – steroids, thiazides, sympathomimetics

Question 17

DKA: Hyperglycemia, Ketosis, Acidosis

Answer 17

• Hyperglycemia (>250 mg/dL)
• Ketosis:
  
  • negative charged ions
  • Anion Gap > 12 mEq/L (ref range: 3-11)
  • Na - (Cl + H3CO)
• Acidosis
  
  • arterial pH ≤ 7.3

Question 18

Management of DKA

Answer 18

• continue until pt is stable:
  
  • glucose: 150-250 mg/dL
  • acidosis resolved
  • insulin reduced 0.5-0.1 units/kg/hr
• Give long acting insulin as soon as pt is eating (allow overlap–SubQ and IV)