Treatment of Diabetes: Insulins

Question 1

Normal basal pattern of insulin secretion

Answer 1

• Basal secretion of insulin occurs without exogenous stimuli to maintain a certain concentration of insulin at all times, even while fasting.
• Stimulated insulin secretion occurs in response to exogenous stimuli.
• A plasma glucose of greater than 100 mg/dL is the most potent stimulus for insulin release.

Question 2

Characteristics of stimulated insulin release

Answer 2

• Initial release of insulin in response to ingestion of food is termed “first-phase insulin secretion”.
  
  • This occurs approximately 8-10 minutes after food is ingested
• If glucose concentrations remain high, insulin release drops off but begins to rise again to a steady level termed “second-phase insulin secretion”.
• peripheral insulin concentration increases and peaks 30-45 minutes after starting a meal

Question 3

Glucose response to physiologic insulin secretion

Answer 3

• The postprandial glucose concentration falls rapidly in response to insulin, reaching baseline levels 90-120 minutes after eating.
• Physiologic insulin secretion consists of a constant basal level of insulin secretion and prandial secretion associated with ingestion of food.

Question 4

Major classes of insulins

Answer 4

• basal
• pranidal
• biphasic (mixed)

Question 5

General characteristics of basal insulins

Answer 5

• Long acting insulin analogues: given once daily for basal coverage
• Intermediate acting NPH (neutral protamine Hagedorn): twice daily injections, treats mid day hyperglycemia associated with lunch, acts as basal insulin

Question 6

General characteristics of prandial insulins

Answer 6

• Rapid acting insulin analogue: injected just before a meal to prevent hyperglycemia, also used in insulin pumps and IV infusions
• Short acting human insulin: administered before meals to prevent hyperglycemia.
  
  • Can be sub-q or IV if DKA, hyperosmotic hyperglycemic state, or other inpatient cases

Question 7

General characteristics of biphasic (mixed) insulins

Answer 7

Human and analogues: attain short term coverage for meals and longer basal effects.

Question 8

Basal insulins: pharmacokinetics (onset, peak, duration of action)

Answer 8

• NPH
  
  • onset = 2 - 4 hr
  • peak = 6 - 7 hr
  • duration =10 - 20 hr
• Detemir
  
  • onset = 1 hr
  • duration = 10 - 20 hr
• Glargine
  
  • onset = 1.5 hr
  • duration = ~24 hr

Question 9

Prandial insulins: pharmacokinetics (onset, peak, duration of action)

Answer 9

• Humalog, Novolog, Apidra
  
  • onset = 5 - 15 min
  • peak =1 - 1.5 hr
  • duration = 3 - 5 hr
• Regular (U100)
  
  • onset = 30 - 60 min
  • peak = 2 hr
  • duration = 6 - 8 hr

Question 10

Biphasic insulins: pharmacokinetics (onset, peak, duration of action)

Answer 10

• Humalog 75/25
  
  • onset = 5 - 15 min
  • peak = 30 - 90 min
  • duration = 15 - 18 hr
• Humalog 50/50
  
  • onset = 5 - 15 min
  • peak = 30 - 90 min
  • duration = 15 - 18 hr
• Novolog
  
  • onset = 10 - 20 min
  • peak = 1.5 - 3 hr
  • duration = 10 - 20 hr

Question 11

Standard of care for T1D glycemic management

Answer 11

• intensive multiple-dose insulin therapy, which provides more physiologic replacement of insulin
• This also called “basal-bolus” therapy, and allows patients more flexibility in the timing, size and composition of meals.

Question 12

T1D tx example: gliargine + rapid-acting insulin

Answer 12

• Glargine injected once daily (at bedtime or before breakfast) provides basal coverage for ~24 hours.
• “Meal boluses” consisting of set doses of rapid-acting insulin or doses calculated using carbohydrate content of the meal are administered just before each meal.
• Additional insulin is often added to correct high pre-meal blood glucose values using a “correction factor” or “sensitivity factor”.

Question 13

T1D tx example: Glargine + NPH + rapid-acting

Answer 13

• this regimen uses the NPH peak to cover lunch, and eliminates the need for a lunchtime injection which can be troublesome for patients at school or work.
• Detemir or Glargine then provides basal coverage overnight and into the next day.

Question 14

T1D tx examples

Answer 14

1. morning/evening glargine (24-hr basal coverage) + pre-meal rapid acting insulin analog (post-prandial coverage)
2. morning NPH (peak cover post-prandial lunch) + evening glargine (overnight/next day basal coverage) + pre-breakfast/dinner rapid acting insulin analog (post-prandial coverage)

Question 15

Clinical scenarious prompting use of insulin therapy in T2D

Answer 15

1. Pt.s experiencing marked weight loss with fasting blood glucoses >250 mg/dL, random glucoses of >300 mg/dL, and/or hemoglobin A1c of >10%
   
   1. signs of severe insulin deficiency
2. Pt.s w/ hospital admission for hyperglycemic hyperosmolar state or diabetic ketoacidosis.
   
   1. Pt.s placed on intravenous insulin infusions, and discharged on subcutaneous insulin regimens

Question 16

General characteristics of inpatient management of DM

Answer 16

• Inpatient hyperglycemia is associated with significant adverse outcomes
• insulin is preferred agent for control of inpatient hyperglycemia

Question 17

Goals/management of inpatient glucose in critically ill vs. noncritically ill patients

Answer 17

• Critically ill
  
  • goals: BG between 140-180 mg/dL
  • tx: start IV insulin @ BG > 180 mg/dL
• Noncritically ill
  
  • goals: random BG < 180 mg/dL; premeal BG < 140 mg/DL
  • tx: scheduled subcutaneous insulin
    
    • insulin analogs preferred