Insulins

Question 1

1. Describe the physiologic pattern of insulin secretion.

Answer 1

endocrine pancreas secretes about 30 units of insulin a day, even when not eating. Basal secretion of insulin occurs without exogenous stimuli to maintain a certain concentration of insulin at all times. Stimulated insulin secretion (food!) occurs in response to exogenous stimuli.

First Phase: Initial, acute rise in insulin. Happens rapidly in response to ingested food, then drops off.

Second Phase: Slower, longer rise in insulin in response to prolonged hyperglycemia. This occurs approximately 8-10 min after food is ingested: peripheral insulin concentration increases and peaks 30-45 minutes after starting a meal.

Question 2

4. Describe 2 situations in which insulin therapy is used in type 2 diabetes.

Answer 2

Insulin treatment for Type II is usually started when lifestyle modifications and non-insulin combinations don’t achieve target blood glucose levels. It is also started when the patient has contraindications for using other diabetes medications (renal dysfunction, hepatic dysfunction, congestive heart failure). Insulin can be started earlier or later in the progression of therapies depending on various factors (some data suggests that starting insulin earlier can help preserve some beta-cell function).

ALWAYS use insulin for Type II Diabetes when:
You see signs of insulin deficiency on presentation
Weight loss
Fasting blood glucose >250 mg/dL
Random blood glucose >300 mg/dL
Hemoglobin A1c >10%
Patient requires hospital admission for diabetic emergency
Hyperglycemic hyperosmolar state
Diabetic ketoacidosis

Question 3

5. Give an example of physiologic insulin dosing for type 1 diabetes.

Answer 3

Standard of care for T1D is intensive multiple-dose insulin therapy in an effort to more closely mimic physiologic insulin release. Also called “basal-bolus” therapy, it lets patients have more flexibility in terms of timing, sizing, and meal composition.

KEY POINT: You want to PREVENT hyperglycemia by getting AHEAD of the game!! If your blood sugar is too high at lunch, means your insulin was TOO LOW at breakfast! Need to adjust ahead of time, e.g. don’t necessarily need to increase insulin at lunch, but need to increase at BREAKFAST so it doesn’t get high in the first place! (See question 4 of Friday’s review).

DAWN PHENOMENON: hyperglycemia in response to an early morning surge in growth hormone.

Take Glargine at bedtime or pre breakfast to give a basal insulin level.
take rapid acting, before each meal.

Question 4

6. Explain the basic principles of inpatient management of diabetes.

Answer 4

Hyperglycemia in hospitalized patients:
Diagnosed or undiagnosed diabetes
Consequence of the physiologic stress of illness or surgery
Result of medications, or enteral or parenteral nutrition

Rational: Inpatient hyperglycemia is associated with significant adverse outcomes. Controlling hyperglycemia improves outcomes such length of stay, infection incidence, and in some studies, ICU and in-hospital mortality.

Guidelines

Critically Ill Inpatients

• Start insulin if BG >180 mg/dL,
• Maintain BG at 140-180 mg/dL

If they come in with DKA or hyperosmotic state, they have to leave the hospital with insulin.

If they come in on other diabetic meds, stop them and use insulin

Question 5

glucose stimulated insulin release steps

Answer 5

Glucose taken up by glucose transporter.

Increased production of ATP blocks an ATP-sensitive K+ channel, thereby closing it and depolarizing the cell.

Depolarization opens VGCC and Ca+2 rushes into the cell.

Calcium influx allows granules containing insulin to fuse with the cell membrane and release insulin into the blood!

Question 6

Rapid-Acting Insulin

Answer 6

Lispro, Aspart, Glulisine
Found that changing certain amino acids or amino acid positions on one of the insulin chains can make the insulin act way faster.

Onset of action = 5-15 minutes with a peak at 1-1.5 hours and a duration of 3-5 hours
Really good for immediate insulin control (right before you eat – less “planning”)
Sub-Q injection or in an insulin pump
Monomers dissociate shortly after injection – rapid activation
Need to have your meal on the table before you inject your rapid-acting insulin!

Insulin has two chains: A (21 amino acids) and B (30 amino acids)
Lispro: 28th amino acid of B chain (lysine) switched with 29th amino acid of B chain (proline)
Aspart: 29th amino acid of B chain changed to aspartate
Glulisine: 3rd amino acid of B chain (lysine) switched with 29th amino acid of B chain (glutamate)

Question 7

Regular Insulin

Answer 7

Humulin R, Novolin R

Recombinant human insulin; small amounts of zinc improve stability & shelf-life

Also short-acting
Onset of action = 30-60 minutes with a peak of 2 hours and duration of 6-8 hours
Sub=Q injection or IV

Take insulin half an hour before you eat, and then you can eat!

Problem: If you get distracted and don’t eat in ½ an hour, you’ll be hypoglycemic

Question 8

Intermediate-acting Insulin (NPH)

Answer 8

Onset of action delayed compared to other insulins by adding soluble crystalline zinc insulin with protamine zinc insulin

Onset of action = 2-4 hours with a peak at 6-7 hours and a duration of 10-20 hours

Can use it as a basal insulin if you inject 2x a day

Only insulin that comes as a cloudy solution

Can use in combination with other insulins (in same syringe)

Question 9

Long-Acting Insulin

Answer 9

Glargine, Detemir (Insulin analogues)

Added arginines in Glargine = more soluble in an acidic environment  when it is injected into the neutral pH environment of subcutaneous tissue, it forms precipitates that slowly release insulin into the circulation

Onset of action = 1-1.5 hours with no real peak and a duration of 24 hours (Glargine) or 17 hours (Detemir)
Used to simulate basal insulin secretion
Sub-Q injection only

CANNOT MIX in same syringe with any other insulin!!!
Makes other insulins precipitate

Question 10

Insulin Preparations (Mixes)

Answer 10

Allows you to mix NPH with regular insulin
Cover a meal AND have basal coverage
NPH + regular - inject 30 minutes QAC
70/30 (70% NPH, 30% regular)
50/50 (50% NPH, 50% regular)
Insulin analog premixes - inject 15 minutes QAC
Intermediate plus humalog
75/25 (75% NPL, 25% humalog)
50/50 (50% NPL, 50% humalog)
Intermediate plus novolog
70/30 (70% intermediate-acting, 30% novolog)
Why use?
If patient has vision loss from diabetes, combination mixes can make it easier for them to take insulin
Don’t need to mix different bottles that are hard to read themselves
Increase compliance
However, injecting insulin is not really physiological, and ratios in mixes are set: if you don’t need that exact ratio, you can run into trouble!