Insulin Basics

There are different types of insulin depending on how quickly they

work, when they peak, and how long they last.
Insulin is available in different strengths; the most common is U-100.
All insulin available in the United States is manufactured in a
laboratory, but animal insulin can still be imported for personal use.

Inside the pancreas, beta cells make the hormone insulin. With each meal,
beta cells release insulin to help the body use or store the blood glucose it
gets from food.
In people with type 1 diabetes, the pancreas no longer makes insulin. The
beta cells have been destroyed and they need insulin shots to
use glucose from meals.
People with type 2 diabetes make insulin, but their bodies don't respond
well to it. Some people with type 2 diabetes need diabetes pills or insulin
shots to help their bodies use glucose for energy.
Insulin cannot be taken as a pill because it would be broken down during
digestion just like theprotein in food. It must be injected into the fat under
your skin for it to get into your blood. In some rare cases insulin can lead to
an allergic reaction at the injection site. Talk to your doctor if you believe
you may be experiencing a reaction.

Types of Insulin

Rapid-acting insulin, begins to work about 15 minutes after

injection, peaks in about 1 hour, and continues to work for 2 to 4
hours. Types: Insulin glulisine (Apidra), insulin lispro (Humalog), and
insulin aspart (NovoLog)

Regular or Short-acting insulin usually reaches the bloodstream

within 30 minutes after injection, peaks anywhere from 2 to 3 hours

after injection, and is effective for approximately 3 to 6 hours. Types:

Humulin R, Novolin R

Intermediate-acting insulin generally reaches the bloodstream

about 2 to 4 hours after injection, peaks 4 to 12 hours later, and is
effective for about 12 to 18 hours. Types: NPH (Humulin N, Novolin N)

Long-acting insulin reaches the bloodstream several hours after

injection and tends to lower glucose levels fairly evenly over a 24-hour
period. Types: Insulin detemir (Levemir) and insulin glargine (Lantus)

Premixed insulin can be helpful for people who have trouble drawing up
insulin out of two bottles and reading the correct directions and dosages. It
is also useful for those who have poor eyesight or dexterity and is
convenient for people whose diabetes has been stabilized on this
combination.

Characteristics of Insulin
Insulin has 3 characteristics:

Onset is the length of time before insulin reaches the bloodstream and
begins lowering blood glucose.

Peaktime is the time during which insulin is at maximum strength in

terms of lowering blood glucose.

Duration is how long insulin continues to lower blood glucose.

Insulin Strength
All insulins come dissolved or suspended in liquids. The standard and most
commonly used strength in the United States today is U-100, which means it
has 100 units of insulin per milliliter of fluid, though U-500 insulin is
available for patients who are extremely insulin resistant.
U-40, which has 40 units of insulin per milliliter of fluid, has generally been
phased out around the world, but it is possible that it could still be found in
some places (and U-40 insulin is still used in veterinary care).

If you're traveling outside of the U.S., be certain to match your insulin

strength with the correct sizesyringe.
http://www.diabetes.org/living-with-diabetes/treatment-andcare/medication/insulin/insulin-basics.html

Reference Range
Insulin is an anabolic hormone that promotes glucose uptake, glycogenesis, lipogenesis, and protein synthesis
of skeletal muscle and fat tissue through the tyrosine kinase receptor pathway. In addition, insulin is the most
important factor in the regulation of plasma glucose homeostasis, as it counteracts glucagon and other
catabolic hormonesepinephrine, glucocorticoid, and growth hormone.
Table 1. Reference Range of Insulin Levels[1] (Open Table in a new window)
Insulin Level

Insulin Level (SI Units*)

Fasting

< 25 mIU/L

< 174 pmol/L

30 minutes after glucose administration

30-230 mIU/L

208-1597 pmol/L

1 hour after glucose administration

18-276 mIU/L

125-1917 pmol/L

2 hour after glucose administration

16-166 mIU/L

111-1153 pmol/L

3 hours after glucose administration

< 25 mIU/L

< 174 pmol/L

*SI unit: conversional units x 6.945

Interpretation
A standard insulin test is positive for endogenous insulin and exogenous insulin. In addition, there is a minimal
cross-reaction with proinsulin and insulinlike growth factors 1 and 2, with the degree of variability depending on
the brand of the testing toolkit and technique used.
Insulin testing is used to assist in identifying causes of hypoglycemia (plasma glucose levels < 55 mg/dL),
especially upon signs and symptoms of hypoglycemia (neurohypoglycopenic and autonomic symptoms). In this
scenario, a 72-hour fasting test is performed. [2]

Insulinoma: High insulin and C-peptide levels

Nonbeta cell tumors: Low insulin and C-peptide levels and high insulinlike growth factor 2 level [3]
Excessive insulin administration: High insulin levels and low C-peptide levels
Insulin secretagogue administration (sulfonylurea and glinides): High insulin and C-peptide levels
Congenital hyperinsulinism (mutation in insulin-secreting gene): High insulin and C-peptide levels
Autoimmunity to insulin or insulin receptor (common in patients receiving insulin or those who have
autoimmune diseases such as systemic lupus erythematosus [SLE] or Hashimoto thyroiditis): Postprandial
insulin is bound to antibodies and dissociated 1 hour later, resulting in an extremely elevated insulin level and
high insulintoC-peptide ratio[4]
Table 2. Interpretation of 72-hour Fasting Test Results [2] (Open Table in a new window)

Condition

Insulin

C-Peptide

Proinsulin

Insulinlike Growth Factor 2

Sulfonylurea

Glucose Level After Administration of Glucagon

Insulinoma

Nonbeta cell tumors

Insulin injection

Sulfonylurea-induced

Conditions associated with elevated insulin levels

Conditions associated with increased insulin resistance[4, 5] (beta cell compensates via hypersecretion of insulin)
include the following:

Obesity
Steroid administration
Acromegaly
Cushing syndrome
Insulin receptor mutation[4]
Type 2 diabetes (early stage)
Conditions associated with increased insulin secretion include the following:

Insulinoma (insulin or proinsulin secreting tumors)

Administration of insulin secretagogues
Excessive administration of insulin is associated with elevated insulin levels.
Conditions associated with decreased insulin excretion include the following [4] :

Severe liver disease

Severe heart failure (liver congestion)
Autoimmunity to insulin or insulin receptor is associated with elevated insulin levels.

Conditions associated with decreased insulin levels

Conditions associated with beta-cell destruction include the following:

Post pancreatectomy
Chronic pancreatitis
Autoimmune destruction
Type 1 diabetes
In type 2 diabetes (late stage), beta cells fail to secrete insulin for maintaining the blood glucose level, owing to
insulin resistance and genetic defect.[6]
Increased insulinlike growth factor levels are associated with nonbeta cell tumors.

Collection and Panels

Method: Radioimmunoassay; enzyme-linked immunosorbent assay (ELISA)

Specifics for collection and panels are as follows:

Specimen type: Blood serum

Container: Vacutainer, red top
Collection method: Venipuncture
Specimen volume: 1 mL
Measure blood glucose and C-peptide level in same sample
An 8-hour fasting specimen required

Other instructions
A 72-hour fasting test is used to identify causes of postabsorptive hypoglycemia. [2]The patient is instructed to
fast, and plasma glucose, insulin, proinsulin, and C-peptide levels are measured every 6 hours until the plasma
glucose level is less than 65 mg/dL, after which the testing frequency is increased to every 1-2 hours. Fasting is
ended when plasma glucose levels are less than 45 mg/dL accompanied by signs and symptoms of
hypoglycemia. At the endpoint, a blood sample is collected and tested for glucose, insulin, proinsulin, Cpeptide, beta-hydroxybutyrate, and sulfonylurea levels. The patient is given 1 mg of intravenous glucagon, and
the response of the blood glucose level is measured.

Background
Description
Biosynthesis[7, 4, 8]
Insulin is a peptide hormone that is secreted from beta cells of the islets of Langerhans in the pancreas. It is
initially synthesized in endoplasmic reticulum and Golgi apparatus as proinsulin; it is then cleaved to insulin and
C-peptide. Although insulin and C-peptide are cosecreted in equal molar proportions, the ratio of serum insulin
to C-peptide is 1:5-15. Fifty to sixty percent of insulin is extracted by the liver before it reaches systemic
circulation, and it has a half-life of only 4 minutes. In contrast, C-peptide and proinsulin are excreted via the
kidney.[6]
Function
Insulin is an anabolic hormone that promotes glucose uptake, glycogenesis, lipogenesis, and protein synthesis
of skeletal muscle and fat tissue through the tyrosine kinase receptor pathway. In addition, insulin is the most
important factor in the regulation of plasma glucose homeostasis, as it counteracts glucagon and other
catabolic hormonesepinephrine, glucocorticoid, and growth hormone.
Secretion
In normal physiology, insulin secretion is induced by elevated plasma glucose levels. Glucose diffuses to beta
cells through glucose transporter 2 (GLUT2) and activates the glycolysis pathway, leading to elevated
adenosine triphosphate (ATP) levels. Increasing ATP levels induce ATP-sensitive K + channels to shut down and
subsequently stimulate depolarization of the beta-cell membrane. Then, voltage-gate Ca 2+ channels are opened
to increase cytosolic Ca2+ and trigger insulin exocytosis.[6] However, high insulin levels in a hypoglycemic state
have been found in a hypersecretory state; an example is insulinoma, in which insulin is secreted in at a high
rate independent from the plasma glucose level.

Interestingly, oral administration of glucose is more effective in increasing insulin secretion than intravenous
glucose (called "incretin effect"). Carbohydrate meals potentiate insulin secretion through multiple
gastrointestinal hormones (incretin hormones), including cholecystokinin, glucagonlike peptide-1 (GLP-1), and
gastric-inhibiting polypeptide (GIP).[6, 9]

Indications/Applications
Insulin testing is used to assist in identifying causes of hypoglycemia (plasma glucose levels < 55 mg/dL),
especially upon signs and symptoms of hypoglycemia (neurohypoglycopenic and autonomic symptoms). In this
scenario, a 72-hour fasting test is performed. [2]
Insulin testing is also used to assist in diagnosing early type 2 diabetes, in which there is a relatively increased
production of insulin with a concurrent increase in blood glucose levels.
In addition, insulin testing is used to help differentiate type 1 and type 2 diabetes.

Considerations
Insulin levels may be falsely elevated by the following:

Amino acid (leucine, arginine, and lysine)

Steroid
Insulin secretagogue (sulfonylurea and glinide)
Estrogen[10]
Beta2 agonist
Insulin levels may be falsely decreased by the following:

Acarbose, metformin, octreotide, and beta-blocker

Hemolysis (insulin-degrading enzyme in red blood cell released) [4]
Hemodialysis

http://emedicine.medscape.com/article/2089224-overview#showall

Table 1. Insulin Types[1] (Open Table in a new window)

Insulin Type

Onset

Peak

Duration

Ultra short acting: insulin lispro, insulin aspart, insulin glulisine

12-30 min

0.5-3 hr

3-5 hr

Short acting: regular insulin

30 min

2.5-5 hr

4-24 hr

Intermediate acting: insulin NPH

1-2 hr

4-12 hr

14-24 hr

Long acting: insulin glargine, ultralente insulin

3-4 hr

No defined peak

24 hr