Insulin

- Oral glucose load is more efficient than IV glucose in raising serum insulin levels

-Glucose digestion starts in the mouth

- Abdominal injections of insulin are absorbed faster than those at other body sites and are more consistent

- Cloudy insulin bottles should be rolled rather than shaken to mix the contents

- Shaking the bottle can cause bubbles and lead to an inaccurate dosing

- Heat and massage can increase subcutaneous absorption and cooling can decrease absorption

- Insulin sites should be rotated to prevent lipodystrophy

- Lipodystrophy occurs when the same site is repeatedly used for injection

- Lipodystrophy is an atrophy or hypertrophy of the tissue, which can interfere with insulin absorption

- Illness and stress increase the need for insulin

- Hypokalemia can result from large doses of insulin

Adverse Reactions

Hypoglycemic reactions

- Insulin shock can occur from too much insulin

- Symptoms of hypoglycemic reaction disappear immediately with the administration of sugar

- Symptoms of hypoglycemic reactions (insulin shock):

- Nervousness

- Trembling

- Lack of coordination

- Cold and clammy skin

- Headache

- Incoherent or combative nature

- The Somogyi effect is a hypoglycemic condition that occurs between 2-4 a.m.

- Caused by a rapid decrease in blood glucose during nighttime hours, which stimulates the release of cortisol, glucagon, and epinephrine

- The Somogyi effect can be prevented by decreasing the bedtime insulin dosage

Hyperglycemic reactions

- Ketoacidosis and hyperglycemia can result from insufficient insulin

- Symptoms of ketoacidosis include polyuria, extreme thirst, fruity breath odor, Kussmaul breathing (deep, rapid, labored, dyspneic), rapid, thready pulse, poor skin turgor, and blood glucose >250mg/dL

- Hyperglycemia upon awakening is known as the dawn phenomenon

- Managing the dawn phenomenon is to ==increase bedtime dose insulin==

- Symptoms include headache, night sweats, and nightmares

- Ketoacidosis results from excessive build up of ketones in the body

- Fat metabolism results in the production of ketones which are used as an alternative fuel source when there is no glucose metabolism

Types of Insulin

Rapid-acting and short-acting insulin are clear solutions with no added substances to prolong action. Intermediate-acting insulins are cloudy and may contain zinc or proteins to prolong the action of insulin

Rapid-Acting Insulin

- R-A insulin act faster than regular insulin and should be administered within 10-15 minutes before mealtime. Food should be present before the administration of insulin

- Patients who take R-A insulin usually require intermediate acting insulin as well

Types of R-A Insulin

The Acronym GOAL can be used to remember the rapid-acting insulin types

- Insulin Glulisine

- Insulin Aspart

- Oral Inhalation Insulin

- Insulin Lispro

Short-Acting Insulin

- S-A insulin has an onset of 15-30 minutes with a peak action in 1.5-3.5 hours and a duration of 4-12 hours

- Regular insulin is a S-A insulin that can be given IV or SQ

- Regular insulin should be given 30-60 minutes before meal time

- ==Regular can be combined with NPH in commercially premixed bottles

- Combinations come as 70NPH/30R or 50NPH/50R

Intermediate-Acting Insulin

- I-A insulins have a longer onset onset time than short acting insulins

- ==I-A insulin has an onset of 1-2 hours, a peak action of 4-12 hours, and a duration of 14-24 hours

- Neutral Protamine Hagedorn (NPH) is an intermediate-acting insulin that contains the protein protamine which prolongs the action of insulin

- Intermediate-acting insulins are the only type (rapid, short, intermediate, long) that are innately cloudy

Long-Acting & Ultra-Long Acting Insulin

- Long-acting and UL-acting insulins have the longest onset times and longest duration of actions

- These insulins provide basal insulins which prevent high glucose between meals and overnight

- These insulins have a lower incidence of nocturnal hypoglycemia because of the sustained release

Types of L-A Insulins

Insulin Detemir

- Onset: 6-8 hours

- Total duration 24 hours

Types of UL-A Insulins

Insulin Glargine

- Onset: 1-1.5 hours

- Glargine insulin provides steady, continuous insulin release over 24 hours

- Glargine is usually administered once a day at bedtime

- More pain is associated with this insulin compared to NPH

Insulin Degludec

- Onset: 1 hour

- Peak action is at 12 hours

- Total duration: 42 hours

Pharmacokinetics & Pharmacodynamics

Pharmacokinetics

- All insulin can be given SQ but only regular insulin can be given IV

- Insulin is metabolized by the liver and excreted in urine

Pharmacodynamics

- The peak action of insulin is important because of the possibility of a hypoglycemic reaction (insulin shock) occurring during that time

- Signs of hypoglycemic reaction:

- Nervousness

- Tremors

- Confusion

- Diaphoresis

- Tachycardia

- Simple-sugar foods and drinks should always be kept with the patient to prevent hypoglycemic shock

- If the patient is unable to ingest fast-acting carbs, glucagon can be given to release glucose from glycogen stores

- Glucagon can raise blood glucose within 10 minutes

## Drug Interactions

- Thiazide diuretics, glucocorticoids, thyroid agents, and estrogen can all raise blood glucose

- Can cause secondary DM in prediabetic patients

- Tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), aspirin products, and oral anticoagulants all decrease blood glucose

- Beta-blockers, sulfonylureas, meglitinides, and alcohol can have additive hypoglycemic effects

- Beta-blockers inhibit the SNS and hepatic glucose productions

- Beta-blockers can also mask the symptoms of insulin shock (diaphoresis, tremors, tachycardia, palpitations)