INSULIN THERAPY IN TYPE 1 DM: REVIEW

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INSULIN THERAPY IN TYPE 1 DM REVIEW

• ROLA SAAD, M.D.
• PEDIATRIC ENDOCRINOLOGY
• UNSOM

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The primary structure of insulin is made from two
polypeptide chains named subunit A and B. Subunit
A consists of 21 amino acids, whereas subunit B
consists of 30 amino acids. These chains are
connected by two disulfide bridges. Insulin also
forms quaternary structure by creating diamers
using hydrogen bonds and hexamers by bonding with
two zinc ions. Insulin The final product of
insulin only consists of 51 amino acids so it is
quite small compared to other proteins. Insulin's
small size allows it to be a ligand for other
proteins appropriately named insulin receptors.
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The insulin gene is only expressed in B-cells in
the pancreas. When this gene is expressed,
pre-mRNA called proinsulin is made. This
precursor to insulin is only one polypeptide
chain and it contains both subunit A and subunit
B in it. The A subunit is located at the
C-terminus whereas the B subunit is located at
the N-terminus The C subunit, that is cut out of
the end product, is cut out of the polypeptide by
specific proteases
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Computer-generated image of six insulin molecules
assembled in a hexamer, highlighting the
threefold symmetry, the zinc ions holding it
together, and the histidine residues involved in
zinc binding. Insulin is stored in the body as a
hexamer, while the active form is the monomer.
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Insulin absorption ? Insulin activity profiles
show substantial variability both day to day in
the same individuals and between individuals,
particularly children. ? The onset, peak effect
and duration of action depend upon many factors
which significantly affect the speed and
consistency of absorption. ? Young people and
care providers should know the factors which
influence insulin absorption such as Age
(young children, less subcutaneous
fat?faster absorption) . Fat mass (large
subcutaneous fat thickness , lipohypertrophy,
also with rapid-acting analogs ?slower
absorption).
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Dose of injection (larger dose ? slower
absorption). Site and depth of sc injection
(abdomen faster thanthigh no good data exist on
absorption from thigh vs. buttock). Sc versus
im injection (im injection ? faster absorption in
thigh. Accidental im injections can cause
variable glucose control . Exercise (leg
injection, leg exercise ? faster absorption.
Insulin concentration, type and formulation
(lower concentration?faster absorption).
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Ambient and body temperature (higher
temperatures ?faster absorption). ? In general,
the absorption speed of rapid-acting analogs is
less affected by the above mentioned factors . ?
There is no significant difference in the
absorption of glargine from abdomen or thigh.
Exercise does not influence glargine absorption
. ? There is a risk of hypoglycemia if injecting
glargine intramuscularly, particularly in young
and lean individuals . Note Faster absorption
usually results in shorter duration of action.
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Devices for insulin delivery Insulin syringes.
Pen injector devices.
Automatic injection devices.
Jet injectors.
Continuous subcutaneous insulin infusion (CSII).
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Problems with injections ? Local hypersensitivity
reactions to insulin injections are uncommon but
when they do occur, formal identification of the
insulin (or more rarely preservative) responsible
may be possible with help from the manufacturers.
A trial of an alternative insulin preparation may
solve the problem. If true allergy is suspected,
desensitization can be performed using protocols
available from the manufacturers. Adding a small
amount of corticosteroids to the insulin may help.
? Lipohypertrophy with the accumulation of fat in
lumps underneath the skin are common
in children. ? Lipoatrophy is now uncommon since
the introduction of highly purified insulins, but
has been described also with the newer analogs.
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? Painful injections are a common problem
in children. Check angle, length of the needle,
and depth of injection to ensure injections are
not being given intramuscularly and that the
needle is sharp. Reused needles can cause more
pain. Indwelling catheters (Insuflon) can
decreasei njection pain. ? Leakage of insulin is
common and cannot be totally avoided. Encourage
slower withdrawal of needle from skin, stretching
of the skin after the needle is withdrawn, or
pressure with clean finger over the injection
site.
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? Bruising and bleeding are more common
after intramuscular injection or tight squeezing
of the skin.Use of thinner needles have shown
significantly less bleeding at the injection
site. ? Bubbles in insulin should be removed
whenever possible. If the bubble is not big
enough to alter the dose of insulin it should not
cause problems. When using insulin pens, air in
the cartridge can cause drops of insulin
appearing on the tip of the pen needle, if
withdrawn too quickly.
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Currently, children are prescribed human insulins
instead of porcine or bovine insulin because of
low immunogenicity, but in many countries these
are being superceded by analogs.
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LANTUS GLARGINE
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LANTUS (insulin glargine rdna origin injection)
is produced by recombinant DNA technology
utilizing a non-pathogenic laboratory strain of
Escherichia coli (K12) as the production
organism. Insulin glargine differs from human
insulin in that the amino acid asparagine at
position A21 is replaced by glycine and two
arginines are added to the C-terminus of the
B-chain.
Chemically, it is 21A- Gly-30Ba-L-Arg-30Bb-L-Arg-h
uman insulin and has the empirical formula
C267H404N72O78S6 and a molecular weight of 6063.
LANTUS (insulin glargine rdna origin injection)
has a pH of approximately 4.
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Glargine Lack of an accumulation effect of
glargine given on consecutive days has been shown
in one Study. The effect of glargine lasted for
up to 24 hours in adults, however, a waning
effect can be seen approximately 20 hours after
injection. Some children report a burning
sensation when injecting glargine due to the acid
pH. A review of pediatric studies over six
years of once daily insulin glargine found a
comparable or small improvement in HbA1c but a
reduced rate of hypoglycemia, and a greater
treatment satisfaction in adolescents compared to
conventional basal insulins.
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LEVEMIR DETEMIR
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LEVEMIR (insulin detemir rDNA origin injection)
is a sterile solution of insulin detemir for use
as a subcutaneous injection. Insulin detemir is a
long-acting (up to 24-hour duration of action)
recombinant human insulin analog. LEVEMIR is
produced by a process that includes expression of
recombinant DNA in Saccharomyces cerevisiae
followed by chemical modification.
Insulin detemir differs from human insulin in
that the amino acid threonine in position B30 has
been omitted, and a C14 fatty acid chain has been
attached to the amino acid B29. Insulin detemir
has a molecular formula of C267H402O76N64S6 and a
molecular weight of 5916.9.
LEVEMIR has a pH of approximately 7.4.
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Detemir A study with detemir in adults found
the time of action to be between 6 and 23 hours
when doses between 0.1U/kg and 0.8 U/kg were
given. In a pediatric study, 70 of the patients
used detemir twice daily. In adults, studies
with detemir have shown weight reduction or less
weight gain, which has been observed also in
children and adolescents.

• Detemir is characterized by a more reproducible
• pharmacokinetic profile than glargine in children
  and adolescents with type 1 diabetes .

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Rapid acting insulin analogs Several novel
insulin analogs have been developed. Three rapid
acting types are currently available for children
(aspart, glulisine, lispro). They have a
rapid onset and shorter duration of action than
regular insulin. The rapid acting analogs can
when necessary be given immediately before meals
because there is evidence that the rapid
action not only reduces postprandial
hyperglycemia but nocturnal hypoglycemia may also
be reduced. offer the useful option of being
given after food when needed (e.g. infants and
toddlers who are reluctant to eat). give a
quicker effect than regular insulin when treating
hyperglycemia, with or without ketosis, including
sick days. are most often used as prandial or
snack boluses in combination with longer acting
insulins. are most oftenly used in insulin
pumps.
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HUMOLOG
(insulin lispro injection, USP rDNA origin)
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HUMALOG (insulin lispro injection, USP rDNA
origin) is a rapid-acting human insulin analog
used to lower blood glucose. Insulin lispro is
produced by recombinant DNA technology utilizing
a non-pathogenic laboratory strain of Escherichia
coli. Insulin lispro differs from human insulin
in that the amino acid proline at position B28 is
replaced by lysine and the lysine in position B29
is replaced by proline. Chemically, it is
Lys(B28), Pro(B29) human insulin analog and has
the empirical formula C257H383N65O77S6 and a
molecular weight of 5808, both identical to that
of human insulin. . Insulin lispro has a pH
of 7.0 to 7.8.
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NOVOLOGINSULIN ASPART rDNA
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NovoLog (insulin aspart rdna origin inj) (insulin
aspart rDNA origin injection) is a rapid-acting
human insulin analog used to lower blood glucose.
NovoLog (insulin aspart rdna origin inj) is
homologous with regular human insulin with the
exception of a single substitution of the amino
acid proline by aspartic acid in position B28,
and is produced by recombinant DNA technology
utilizing Saccharomyces cerevisiae (baker's
yeast). Insulin aspart has the empirical
formula C256H381N65O79S6 and a molecular weight
of 5825.8.
NovoLog (insulin aspart rdna origin inj) has a pH
of 7.2-7.6
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Serial mean serum glucose collected up to 6 hours
following a single pre-meal dose of NovoLog
(insulin aspart rdna origin inj) (solid curve)
or regular human insulin (hatched curve) injected
immediately before a meal in 22 patients with
type 1 diabetes.
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Mean blood glucose profiles following intravenous
infusion of NovoLog (insulin aspart rdna origin
inj) (hatched curve) and regular human insulin
(solid curve) in 16 patients with type 1
diabetes. R represents the time of autonomic
reaction
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Serial mean serum free insulin concentration
collected up to 6 hours following a single
pre-meal dose of NovoLog (insulin aspart rdna
origin inj) (solid curve) or regular human
insulin (hatched curve) injected immediately
before a meal in 22 patients with type 1 diabetes
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How should I store NovoLog (insulin aspart rdna
origin inj) ? All Unopened NovoLog (insulin
aspart rdna origin inj)
Keep all unopened NovoLog (insulin aspart rdna
origin inj) in the refrigerator between 36 to
46F (2 to 8C). Do not freeze. Do not use
NovoLog (insulin aspart rdna origin inj) if it
has been frozen. Keep unopened NovoLog (insulin
aspart rdna origin inj) in the carton to
protect from light.
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NovoLog (insulin aspart rdna origin inj) in
use Vials. Keep in the refrigerator or at
room temperature below 86F (30C) for up to 28
days. Keep vials away from direct heat or
light. Throw away an opened vial after 28 days of
use, even if there is insulin left in the
vial. Do not draw up NovoLog (insulin aspart
rdna origin inj) into a syringe and store for
later use Unopened vials can be used until the
expiration date on the NovoLog (insulin aspart
rdna origin inj) label, if the medicine has
been stored in a refrigerator.
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PenFill Cartridges or NovoLog (insulin aspart
rdna origin inj) FlexPen Prefilled syringe.
Keep at room temperature below 86F (30C) for
up to 28 days. Do not store a PenFill cartridge
or NovoLog (insulin aspart rdna origin inj)
FlexPen Prefilled syringe that you are using in
the refrigerator. Keep PenFill cartridges and
NovoLog (insulin aspart rdna origin inj)
FlexPen Prefilled syringe away from direct heat
or light. Throw away a used PenFill cartridge or
NovoLog (insulin aspart rdna origin inj)
FlexPen Prefilled syringes after 28 days, even if
there is insulin left in the cartridge or syringe.
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NovoLog (insulin aspart rdna origin inj) in the
pump reservoir and the complete external pump
infusion set The infusion set and the infusion
site should be changed at least every 3 days. The
insulin in the reservoir should be changed at
least every 6 days even if you have not used all
of the insulin. Change the infusion set and the
infusion site more often than every 3 days if you
have high blood sugar (hyperglycemia), the pump
alarm sounds, or the insulin flow is blocked
(occlusion).
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APIDRA (insulin glulisine rdna origin inj)
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APIDRA (insulin glulisine rdna origin inj)
(insulin glulisine rDNA origin injection) is a
rapid-acting human insulin analog used to lower
blood glucose. Insulin glulisine is produced by
recombinant DNA technology utilizing a
non-pathogenic laboratory strain of Escherichia
coli (K12). Insulin glulisine differs from human
insulin in that the amino acid asparagine at
position B3 is replaced by lysine and the lysine
in position B29 is replaced by glutamic acid.
Chemically, insulin glulisine is 3B-lysine-
29B-glutamic acid-human insulin, has the
empirical formula C258H384N64O78S6 and a
molecular weight of 5823
APIDRA (insulin glulisine rdna origin inj) has a
pH of approximately 7.3.
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Glucose infusion rates (GIR) in a euglycemic
clamp study after subcutaneous injection of 0.3
Units/kg of APIDRA (insulin glulisine rdna
origin inj) , insulin lispro or regular human
insulin in an obese population.

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Pharmacokinetic profiles of insulin glulisine
and regular human insulin in patients with type 1
diabetes after a dose of 0.15 Units/kg.
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Serial mean blood glucose collected up to 6 hours
following a single dose of APIDRA (insulin
glulisine rdna origin inj) and regular human
insulin. APIDRA (insulin glulisine rdna origin
inj) given 2 minutes (APIDRA (insulin glulisine
rdna origin inj) - pre) before the start of a
meal compared to regular human insulin given 30
minutes (Regular - 30 min) before start of the
meal (Figure 1A) and compared to regular human
insulin (Regular - pre) given 2 minutes before a
meal (Figure 1B). APIDRA (insulin glulisine rdna
origin inj) given 15 minutes (APIDRA (insulin
glulisine rdna origin inj) - post) after start
of a meal compared to regular human insulin
(Regular - pre) given 2 minutes before a meal
(Figure 1C). On the x-axis zero (0) is the start
of a 15-minute meal.
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STORAGE It is best to refrigerate the unopened
vial/cartridge/pen between 36-46 degrees F (2-8
degrees C). Do not freeze. Discard the insulin if
it has been frozen. Unopened insulin may also be
stored at room temperature below 77 degrees F (25
degrees C), but in that case it must be discarded
after 28 days. Opened vials may be stored in
the refrigerator or at room temperature. Opened
cartridges with the delivery device attached
should not be refrigerated but should be kept at
room temperature. Do not store the delivery
device in the refrigerator. Opened pens should
not be refrigerated but should be kept at room
temperature. When stored at room temperature,
opened containers should be kept below 77 degrees
F (25 degrees C), away from direct heat and
light. Discard all opened containers of insulin
glulisine 28 days after opening. If using this
drug in an insulin pump, do not store this drug
in the pump for more than 48 hours. Doing so may
lead to ineffective therapy and high blood
sugars. Do not expose the insulin in your pump to
direct sunlight or temperatures above 98.6
degrees F (37 degrees C).
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Safety of insulin analogs As insulin analogs are
molecules with modified structure compared to
human insulin, safety concerns have been raised
due to changes in mitogenicity in Vitro. Studies
in primary human cultures have not revealed
altered proliferative effects. In 2009, four
epidemiologic studies were published using large
diabetes and cancer databases, investigating the
risk of malignancy in patients treated with
Insulin glargine. A small, but significant
increased risk of cancer, specifically breast
cancer, was identified in patients treated with
insulin glargine alone, a population of mostly
older adults with type 2 diabetes Mellitus.
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Safety of insulin analogs
One of the studies was negative and did not
identify a link between cancer and glargine. In
addition, there was no clear evidence of harm in
type 1 diabetes or in patients taking insulin
glargine in combination with other insulin
analogs. The authors of the studies and the
accompanying editorial caution against
over-interpretation of the limited data available
to date, and state that no firm conclusions can
be drawn. Presently, there are not safety
concerns that would preclude the use of insulin
analogs in the pediatric age group.
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Regular insulin (short acting) Regular soluble
insulin (usually identical to human insulin) is
still used as an essential component of most
daily replacement regimens in many parts of the
world either combined with ? Intermediate-acting
insulin in twice daily regimen. ? As pre-meal
bolus injections in basal-bolus regimens (given
2030 min before meals) together with
intermediate-acting insulin twice daily or
a basal analog given once or twice daily.
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Regular insulins are best suited for IV therapy
and are used in the following crisis
situations Diabetic ketoacidosis. Control of
diabetes during surgical procedures. Rapid-acting
analog insulin can also be given IV . However,
the effect is not superior to that of regular
insulin and it is more expensive.
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NovolinR Regular, Human Insulin Injection (rDNA
origin) USP is a polypeptide hormone structurally
identical to natural human insulin and is
produced by rDNA technology, utilizing
Saccharomyces cerevisiae (bakers' yeast) as the
production organism. Human insulin has the
empirical formula C257H383N65O77S6 and a
molecular weight of 5808 Da.
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Humulin R U-100 is a polypeptide hormone
structurally identical to human insulin
synthesized through rDNA technology in a special
non-disease-producing laboratory strain of
Escherichia coli bacteria. Humulin R (insulin
human recombinant) U-100 has the empirical
formula C257H383N65O77S6 and a molecular weight
of 5808
Humulin R consists of zinc-insulin crystals
dissolved in a clear fluid
The pH is 7.0 to 7.8
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Intermediate acting insulins The action profiles
of these insulinsmake them suitable for twice
daily regimens and for pre-bed dosage
in basal-bolus regimens Two principal
preparations exist ? Isophane NPH (neutral
protamine Hagedorn) insulins. ? Crystalline zinc
acetate insulin (insulin zinc suspensions, IZS or
lente insulins). Isophane insulins are mostly
used in children, mainly because of their
suitability for mixing with regular insulin in
the same syringe, vial or cartridge
without interaction. Lente insulins are
discontinued in many countries. NOTE When
regular insulin is mixed with lente preparations
it reacts with excess zinc, blunting its short
acting properties .
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Humulin is synthesized in a special
non-disease-producing laboratory strain of
Escherichia coli bacteria that has been
genetically altered to produce human insulin.
Humulin N (insulin human recombinant) Human
insulin (rDNA origin) isophane suspension is a
crystalline suspension of human insulin with
protamine and zinc providing an
intermediate-acting insulin with a slower onset
of action and a longer duration of activity (up
to 24 hours) than that of Regular human insulin.
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NOVOLIN N
NPH, Human Insulin Isophane Suspension
(recombinant DNA origin)
This human insulin (recombinant DNA origin) is
structurally identical to the insulin produced by
the human pancreas. This human insulin is
produced by recombinant DNA technology utilizing
Saccharomyces cerevisiae (bakers' yeast) as the
production organism.
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Traditional long acting insulins ? Ultralente
and Ultratard insulins were designed to have a
duration of more than 24 hours to meet basal
insulin requirements, and therefore could be used
in basal-bolus injection regimens. Their action
profile in children appears to be extremely
variable , with dose accumulation effect. If
available, basal insulin analogs are superior
to traditional long-acting insulins.
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Pre-mixed insulin preparations Pre-mixed
insulins (fixed ratio mixtures of pre-meal and
basal insulins) are popular in some
countries particularly for prepubertal children
on twice daily regimens. Although they reduce
potential errors in drawing up insulin, they
remove the flexibility offered by separate
adjustment of the two types. Such flexibility is
especially useful for children with variable
food intake. There is no clear evidence that
pre-mixed insulins in young children are less
effective, but some evidence of poorer metabolic
control when used in adolescents.
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Inhaled insulin This new form of insulin therapy
has been investigated in children above 12 years
of age as part of a study in adults , but was not
approved for clinical use in children. The sale
of inhaled insulin was discontinued in 2007.
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MIXING INSULIN
The manufacturer recommends that glargine
should not be mixed with any other insulin before
injection, but there is some evidence that it can
be mixed with insulin lispro and aspart without
affecting the blood glucose lowering effect or
HbA1c. The manufacturer recommends that
detemir should not be mixed with any other
insulin before injection. There are no available
studies on this.
Insulins from different manufacturers should be
used together with caution as there may be
interaction between the buffering agents. NPH
and Lente insulins should never be mixed.
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? When a mixture of two insulins is drawn up
(e.g. regular mixed with NPH), it is most
important that there is no contamination of one
insulin with the other in the vials. To prevent
this, the following principles apply There is
no uniformity of advice but most often it
is taught that regular (clear insulin) is drawn
up into the syringe before cloudy insulin
(intermediate or long-acting). Vials of cloudy
insulin must always be gently rolled (not shaken)
at least 10, preferably 20 times , to mix the
insulin suspension before carefully drawing it up
into the clear insulin. If the cloudy insulin
is of Lente type the mixture must be administered
immediately, otherwise the regular component
interacts with zinc which blunts the action.
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Insulin concentrations ? The most widely
available insulin concentration is 100 IU/ml (U
100). ? Treatment with U 40 (40 IU/ml), U50 or
other concentrations such as U500 is also
acceptable, subject to availability and special
needs. ? Care must be taken to ensure that the
same concentration is supplied each time new
supplies are received. ? Very young children
occasionally require insulin diluted with diluent
obtained from the manufacturer, but special care
is needed in dilution and drawing up the insulin
into the syringe. Rapid acting insulin can be
diluted to U10 or U50 with sterile NPH diluent
and stored for 1 month for use in pumps for
infants or very young children.
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INSULIN DOSAGE
Insulin requirement is based upon the body
weight, age, and pubertal stage of the child. In
general, the newly diagnosed child requires an
initial total daily insulin dose of 0.5 to 1.0
units/kg. Prepubertal children usually require
lower doses, and the dose requirement may be as
low as 0.25 units/kg for a variable period
following diagnosis. Higher doses are needed in
pubertal children, patients in ketoacidosis, or
in patients receiving glucocorticoid therapy.
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INSULIN DOSAGE
In infants and toddlers who receive their insulin
by syringe, the insulin dose may be so small that
dilution is required to allow for easier and more
precise administration. The smallest dose of
insulin that can be accurately administered
without dilution using a syringe is 0.5 units.
Many insulins can be diluted either at a
specialized pharmacy or at home with proper
training. Specific diluent for many insulin
preparations is available from the insulin
manufacturer. Some insulin pumps can deliver much
smaller doses of insulin, of the order of 0.025
units at a time, often obviating this problem.
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INSULIN DOSAGE
Follow-up visits at least every three months are
required to adjust for the increasing insulin
requirement with continued growth of the child
and increasing insulin deficiency with duration
of diabetes. The family can be taught to make
interim adjustments via telephone consultation.
As a child enters puberty, daily insulin
requirements may increase to more than 1 unit/kg
because puberty increases insulin resistance .
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INSULIN DOSAGE
Balance of insulins To use the different types
of insulin in intensive therapy, the various
functions of exogenous insulin need to be
considered. Basal insulin In children, the
basal insulin requirement (eg, insulin glargine
or Detemir or basal rate of pump) usually is
approximately 40 to 50 percent of the total daily
dose.
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INSULIN DOSAGE
Correction of elevated blood glucose An insulin
correction factor can be used to select an
insulin dose to correct hyperglycemia before
meals or between meals. For rapid-acting insulin,
divide 1500-1800 by the total daily insulin dose.
This calculation estimates the decrease in blood
glucose from one unit of a rapid-acting insulin.
As an example, if the total daily insulin dose is
30 units, then 1 unit of rapid-acting insulin
will decrease the blood glucose approximately by
50 mg/dL. BG-target glucose (100-150)/correction
factor Or can be written as a scale (lt target
range 0 then increase according to correction
factor example lt 150 0u 151-2001u
201-2502u).
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INSULIN DOSAGE
Utilization of ingested carbohydrate A
rapid-acting insulin pre-meal or pre-snack is
used to provide the insulin requirements for the
anticipated consumption of carbohydrates. The
amount of ingested carbohydrate covered by one
unit of rapid-acting insulin is roughly
calculated based upon the total daily insulin
dose and dividing this into 450- 500. As an
example, if the total daily insulin dose is 50
units, then 1 unit of rapid-acting insulin will
cover 10 grams of carbohydrate. For short-acting
(regular) insulin (rarely used in MDI or pump
regimens), divide 450 by the total daily insulin
dose. However, there is a wide range of insulin
to carbohydrate ratios, with more insulin being
required in older children and less in younger
children than indicated by these calculations.
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INSULIN DOSAGE

• On average, 1 unit of insulin is required to
  cover
• 20 grams of carbohydrates in most young children
  (1 to 6 years of age)
• 10 to 12 grams of carbohydrates in older
  prepubertal children
• 8 to 10 grams in pubertal adolescents

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INSULIN DOSAGE
When converting a patient from MDI or
conventional therapy to insulin pump, the initial
dose is dependent on diabetes control and total
daily insulin dose. If control has been
excellent, the initial daily insulin pump dose is
10 to 20 percent less than the previous dose. If
control has been poor, the same total previous
daily dose should be used. One study suggests
patients using detemir insulin may require
greater dose reductions (26 to 33 percent) when
switching from MDI to the insulin pump .
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• Insulin pump The insulin pump (continuous
  subcutaneous insulin infusion) is increasingly
  used in the pediatric population. Insulin pump
  therapy should be considered for patients with
  one or more of the following characteristics
• Recurrent severe hypoglycemia
• Wide fluctuations in blood glucose levels
  (regardless of A1C)
• Suboptimal diabetes control (A1C exceeds target
  range for age)
• Microvascular complications and/or risk factors
  for macrovascular complications
• Good metabolic control, but insulin regimen that
  compromises lifestyle

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DIABETES EDUCATION
Initial management The initial phase begins at
the time of diagnosis. In these first few days,
the family begins to understand the disease
process and is trained to successfully administer
insulin, check blood glucose concentrations,
check for ketonuria, and recognize and treat
hypoglycemia.
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DIABETES EDUCATION
Blood glucose testing Families must master
blood glucose testing with one of many meters
which are easy to use. They are instructed on the
frequency and timing of monitoring depending upon
the needs of their child.
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DIABETES EDUCATION
Basic understanding The diabetes team teaches
the patient and family the cause and treatment of
type 1 diabetes, how to maintain a daily schedule
and record of blood glucose test results, insulin
administration, and the timing and carbohydrate
content of meals and snacks. Insulin
administration Training includes teaching the
family about the different types of prescribed
insulin, how to measure and inject insulin, and
how to rotate injection sites. Family members and
caretakers must learn about the duration and
action of the various types of insulin prescribed
for their child. They must also understand how to
adjust the insulin dose based upon blood glucose
concentrations and carbohydrate intake.
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DIABETES EDUCATION
Hypoglycemia Families are taught to recognize
the signs and symptoms of hypoglycemia. Detection
of hypoglycemia is particularly difficult in the
non-verbal young child and infant in whom the
signs of hypoglycemia are nonspecific. Parents
are trained to check a blood glucose level and,
if this is too low, to intervene with dietary
measures and/or glucagon.
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DIABETES EDUCATION
Ketonuria Families are taught to check urine
for ketones at times of illness and/or if two
consecutive blood glucose readings are greater
than 250 mg/dL (13.9 mmol/L).
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GOALS
Age-specific goals for A1C are lt6 years of age
lt8.5 percent 6 to 12 years of age lt8 percent
13 to 19 years of age lt7.5 percent Over 19
years of age lt7.0 percent Age-specific goals
for blood glucose at bedtime are lt6 years of
age 110 to 200 mg/dL (6.1 to 11.1 mmol/L) 6 to
12 years of age 100 to 180 mg/dL (5.6 to 10
mmol/L) 13 to 19 years of age 90 to 150 mg/dL
(5 to 8.3 mmol/L) Age-specific goals for blood
glucose before meals are lt6 years of age 100 to
180 mg/dL (5.6 to 10 mmol/L) 6 to 12 years of
age 90 to 180 mg/dL (5 to 10 mmol/L) 13 to 19
years of age 90 to 130 mg/dL (5 to 7.2 mmol/L)
88
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89
 The relationship between A1C and eAG is
described by the formula 28.7 X A1C 46.7
eAG.

A1C eAG eAG
mg/dl mmol/l
6 126 7.0
6.5 140 7.8
7 154 8.6
7.5 169 9.4
8 183 10.1
8.5 197 10.9
9 212 11.8
9.5 226 12.6
10 240 13.4
90
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