Insulin Basics There are different types ofinsulindepending 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 thepancreas, beta cells make thehormoneinsulin.
With each meal, beta cells release insulin to help the body use or
store theblood glucoseit gets from food.In people withtype 1
diabetes, the pancreas no longer makes insulin. The beta cells have
been destroyed and they need insulin shots to useglucosefrom
meals.People withtype 2 diabetesmake insulin, but their bodies
don't respond well to it. Some people withtype 2 diabetesneed
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 theproteinin food. It must
be injected into thefatunder your skin for it to get into your
blood.In some rare cases insulin can lead to an allergic reaction
at theinjectionsite. 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 orShort-acting insulinusually 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
insulingenerally 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
insulinreaches 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
InsulinInsulin has 3 characteristics: Onsetis the length of time
before insulin reaches the bloodstream and begins lowering blood
glucose. Peaktimeis the time during which insulin is at maximum
strength in terms of lowering blood glucose. Durationis how long
insulin continues to lower blood glucose.Insulin StrengthAll
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-and-care/medication/insulin/insulin-basics.htmlReference
RangeInsulin 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 LevelInsulin Level (SI Units*)
Fasting< 25 mIU/L< 174 pmol/L
30 minutes after glucose administration30-230 mIU/L208-1597
pmol/L
1 hour after glucose administration18-276 mIU/L125-1917
pmol/L
2 hour after glucose administration16-166 mIU/L111-1153
pmol/L
3 hours after glucose administration< 25 mIU/L< 174
pmol/L
*SI unit: conversional units x 6.945
InterpretationA 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)ConditionInsulinC-PeptideProinsulinInsulinlike Growth
Factor 2SulfonylureaGlucose Level After Administration of
Glucagon
Insulinoma
Nonbeta cell tumors
Insulin injection
Sulfonylurea-induced
Conditions associated with elevated insulin levelsConditions
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 secretagoguesExcessive 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
levelsConditions associated with beta-cell destruction include the
following: Post pancreatectomy Chronic pancreatitis Autoimmune
destruction Type 1 diabetesIn 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 PanelsMethod: 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 requiredOther instructionsA 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, C-peptide,
beta-hydroxybutyrate, and sulfonylurea levels. The patient is given
1 mg of intravenous glucagon, and the response of the blood glucose
level is measured.BackgroundDescriptionBiosynthesis[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]FunctionInsulin 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.SecretionIn
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 Ca2+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/ApplicationsInsulin 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.ConsiderationsInsulin levels may be falsely elevated by
the following: Amino acid (leucine, arginine, and lysine) Steroid
Insulin secretagogue (sulfonylurea and glinide) Estrogen[10] Beta2
agonistInsulin 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
TypeOnsetPeakDuration
Ultra short acting:insulin lispro,insulin aspart,insulin
glulisine12-30 min0.5-3 hr3-5 hr
Short acting:regular insulin30 min2.5-5 hr4-24 hr
Intermediate acting:insulin NPH1-2 hr4-12 hr14-24 hr
Long acting:insulin glargine, ultralente insulin3-4 hrNo defined
peak24 hr
