Introduction to Insulin

Insulin is a drug most associated with diabetes and has proven to be a miracle drug for persons with diabetes. Improvements in insulin are made on a regular basis as new types arrive on the market and combinations of insulin and medication are blended into one injection.  At some time in the future, some of these insulins will be used in a closed-loop system where a continuous glucose meter and an insulin pump can communicate with each other and act like the pancreas in the body which is responsible for insulin secretion and normalization of glucose in the bloodstream.

History of insulin

Insulin was first discovered in 1921, 100 years ago, by a young orthopedic surgeon, Frederick Banting, and his assistant, Charles Best.   In January 1922, a 14-year-old boy dying from diabetes in a Canadian hospital became the first person to receive an insulin injection. Within 24 hours, Leonard’s dangerously high blood glucose levels dropped to near-normal levels.  He lived a healthy life for 13 years dying of pneumonia at 26 years of age.  Insulin initially came from pigs (Novo Nordisk) and cattle (Eli Lilly and company).  In 1978 the first human, manmade insulin was synthesized by David Goeddel and his colleagues.  Only synthesized insulin is used today as they are less allergenic than animal insulins.

What is insulin

Insulin is a hormone produced by the Beta cells and stored in the pancreas; it is secreted into the bloodstream when the body senses the intake of food and begins to work when it encounters glucose or sugar from the food that is eaten.  Insulin can be endogenous or made by the body or insulin can be exogenous or manufactured. Individuals with diabetes may no longer make any insulin, make insufficient insulin, or can no longer use the insulin that is made.   Because of the different kinds of insulin, it can be administered by syringe, pen, or pump.

Insulin Vial & Syringes

Insulin Pen

Insulin Pump

How does insulin work

how does insulin workInsulin acts as a key, opening the channels of the cells of the body to allow the glucose in the bloodstream to enter such cells and be used as energy.

What does insulin do:

  • Allows the cells throughout the body to use glucose for energy
  • Permits glucose uptake by cells in skeletal muscle for physical activity
  • Enables the release of glucose to fuel the brain and nervous system; vital for cognitive activity
  • Keeps glucose in the body at a healthy level and prevents high blood sugar (hyperglycemia) or low blood sugar (hypoglycemia)
  • Stimulates the entry of amino acids (the body’s building blocks) into the cell to promote the protein building necessary for the cell structure and function
  • Enhances fat storage for future use as energy; prevents fat from being used as energy unless needed
  • Promotes the storage of glucose in the liver and muscles as a future energy source; this is called glycogen
  • Prevents the liver from making more glucose when it is not needed.

All of these are primary functions of insulin that are disrupted in the person with diabetes

how our body uses amino acids

Role of insulin in other parts of the body:

  • Promotes increased activity in brain regions associated with learning and memory
  • Controls fluid and sodium levels through excretion in the urine
  • Allows potassium into cells; potassium is important for fluid balance, muscle contraction, and nerve signals.
  • Promotes muscle repair after sickness or injury
  • Converts lipids, a kind of fat, into triglycerides.  Triglycerides can be a source of energy, but a high level of triglycerides can contribute to heart disease.

Triglycerides

How is insulin used:

  • Type 1 Diabetes – Persons with Type 1 Diabetes need an external or exogenous source of insulin to live.  They may have a brief “honeymoon” period where their pancreas still produces insulin but generally that is short-lived.
  • Type 2 Diabetes – Many persons with Type 2 Diabetes use lifestyle changes (exercise and diet) to manage their diabetes.  Some use medications – some of the medications enhances the pancreas’s ability to produce insulin while other medications enhance the body’s muscles’ ability to use the insulin.  Exogenous insulin is used when lifestyle and medications no longer work to control blood glucose levels.

Insulin delivery:

Goal of Insulin TherapyThe pancreas makes and releases a steady stream of insulin (called basal or background insulin) which regulates glucose [Is glucose produced in the liver and released into the bloodstream when not eating. A spike in insulin (called bolus insulin) is released at mealtimes and snack time to cover the glucose in the food eaten.

The goal of insulin therapy is to mimic as much as possible what the pancreas does.  Individuals with Type 1 Diabetes require insulin at least 3 times per day. Some individuals with Type 2 also require insulin 3 times per day to manage their blood glucose levels.

The group of persons with diabetes currently on any insulin or insulin and oral medications was about 29.1 % from 2005-2012.  It had risen since 1999-2004 by about 4%. from 24.8%. According to the CDC in 2015, only 14% of adults with diabetes used insulin and 13% used insulin with oral medication.   The duration of diabetes is much greater for those on insulin than for those on oral medications.  Age is not a factor in the prevalence of insulin use.  Insulin use is less prevalent among Mexican Americans than whites or African Americans.  With insulin use, 31.4 % of people with diabetes had an HbA1c of < 7%, and 61.7% had an HbA1c of <8 %.

Types of insulin and how they vary:

Five types of insulin are in use, based on how long they work in the body.  Categories include rapid-acting, short-acting, intermediate-acting, long-acting, and mixed.  Some insulins look clear while others look cloudy.  Cloudy insulin must be gently rolled between both hands to remix or resuspend the insulin.  If insulin is supposed to be clear but looks cloudy, it should not be used.  If you do not know if your insulin should be clear or cloudy, consult with your diabetes educator, pharmacist, or physician.

Insulins vary in concentration from U100 to U-200, U-300, with U-500 being the most concentrated.  Concentrated insulins are designed for individuals who need larger doses.  Insulin not only varies by duration (how long they last in the body before its effects are worn off), but also (they begin to work) and peak time (when they reach its highest level of action).  The characteristics of various  insulins can be grouped in the following manner:

Types of Insulin, and their Onsets, Peaks, and Duration Times (chart constructed with information contained in literature of:  Cleveland Clinic, and www.diabeteshealth.com)

Type of Insulin

Name of insulin

Onset

Peak

Duration

Rapid-ActingApidra5-15 minutes1-3 hours3-5 hours
Novolog10-15 minutes1-3 hours3-5 hours
Humalog U-100/U-20010-15 minutes1-3 hours3-5 hours
Lyumjev U-100/U-20015-20 minutes1-3 hoursUp to 5 hours
Afrezza powderLess than 15 minutes12-15 minutes3 hours
Admelog15-30 minutes2 hoursLess than 7 hours
Short-ActingNovolin R/ Humulin R, Humulin R 50030-60 minutes2-4 hours5-8 hours
Intermediate-ActingNovolin N, Humulin N1-2 hours4-12 hours14-24 hours
Long-ActingLevemir1 hour3-14 hoursUp to 24 hours
Lantus, Basaglar3-4 hoursNo peakUp to 24 hours
Toujeo6 hoursNo peakUp to 36 hours
Tresiba1 hourNo peakUp to 42 hours
XultophySeveral hoursNo peak24 hours
SoliquaSeveral hoursNo peak24 hours
Mixed (rapid & intermediate, mixed)70/300.5-1 hour2-12 hours10-16 hours
50/500.5-1 hour2-12 hours10-16 hours
Humalog Mix 75/255- 20 minutes1-2 hours10-16 hours
Humalog Mix 50/505-20 minutes1-2 hours10-16 hours
Novolog Mix 70/305-20 minutes1-2 hours10-16 hours

Insulin use

All insulins are available in a vial to be used in a syringe and quite a few come in disposable or cartridge refill pen format.  Only the 3 rapid-acting insulins, Apidra, Novolog, and Humalog, can be used in insulin pumps.  The pump automatically delivers small amounts of insulin every few minutes acting like a basal dose; as a result, longer-acting insulins are not used.  The pump user can additionally provide bolus doses with a press of a button and release as many insulin units as needed to cover their meal or snack.

Storage requirements

Insulins vary vastly by the length of storage time permitted when open and unopened.   When opened this can range from 14 days to 42 days, depending on the insulin and the format (pen or vial). Insulin can be stored at room temperature when opened (56 degrees to 80 degrees).  Store the remainder of the insulin in the refrigerator not to exceed the expiration date.  Rotating insulins whether in vials or pens is a good idea so they do not expire before use.  To maximize shelf-life, place insulins on the center shelf of the refrigerator with the temperature being 36 degrees to 46 degrees.  Insulin, when unopened, generally expires after 1 year.

References: