Insulin therapy Dr. A. R. GOHARIAN Endocrinologist
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type 1 diabetes The loss of pancreatic function is a hallmark
for the diagnosis of T1DM and is the reason, insulin is a necessary
treatment modality for patients with that form of the disease. vol
32, No 2, 2014. clinical Diabetes
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Indications of Insulin therapy Most people with type 1 diabetes
should be treated with multiple-dose insulin (MDI) injections ( 3 4
injections per day of basal & prandial insulin) or continuous
subcutaneous insulin infusion (CSII). [A]
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T2 DM Type 2 diabetes is also partially defined by a loss of
pancreatic function. At the time of diagnosis of type 2 diabetes, ~
50% of pancreatic function is already lost.
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T2 DM This is a progressive loss that continues throughout
treatment, leading to poor glycemic control and its associated
complications. The continued decline of -cell function results in
the need for medication(s) and eventually exogenous administration
of insulin for type 2 diabetes.
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T2DM Many patients with type 2 diabetes eventually require and
benefit from insulin therapy. The progressive nature of type 2
diabetes and its therapies should be regularly and objectively
explained to patients.
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T2DM & Insulin A patient centered approach to insulin
therapy is essential to ensure optimal outcomes and safety given
the varying levels of evidence regarding the use of insulin.
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Short-term studies comparing insulins show that a high
percentage of people with established type 2 diabetes not well
controlled with oral therapies can achieve blood glucose control to
target, and without high rates of hypoglycemia.
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T2DM & Insulin Insulin products available on the U.S.
market include : rapid- short- intermediate-, and long acting
products as well as premixed formulations.
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Basal Insulin Basal therapy includes long- and intermediate
acting insulin products used to mimic physiological insulin
secretion in the absence of food.
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Bolus Insulin Rapid- and short-acting insulin products
constitute bolus therapy, which is used to mimic the secretion of
insulin from the pancreas in response to food. ( postprandial
)
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Insulin delivery There are currently four delivery Options
available for insulin administration, including : - subcutaneous
injections, - continuous subcutaneous insulin infusion (CSII), -
insulin patch pumps, - and intravenous infusion.
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ADA Standards of Medical Care in Diabetes2015 Although oral
therapy is generally the preferred option for most patients with
type 2 diabetes at diagnosis, the progressive loss of -cell
function means that insulin replacement therapy will eventually
become necessary for many patients.
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ADA Standards of Medical Care in Diabetes2015 Multiple factors
should be taken into account when assessing diabetes control and,
subsequently, considering the initiation and impact of insulin
therapy : - the patients A1C level and - self-monitoring of blood
glucose (SMBG) records, - in combination with patient
interviews.
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ADA/EASD 2015 Position Statement The ADA/EASD guidelines
support the use of patient specific insulin therapy to achieve a
glycemic profile as close to normal as possible while minimizing
adverse effects such as weight gain and hypoglycemia.
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ADA/EASD 2015 Position Statement In accordance with the ADA
standards of care, the ADA/EASD generally recommends oral therapy
as first-line treatment for patients newly diagnosed with type 2
diabetes, typically initiating with one agent.
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After ~ 3 months of monotherapy, providers may consider a
second oral agent, the addition of a glucagon-like peptide-1
(GLP-1) receptor agonist, or the addition of basal insulin if
glycemic goals are not attained.
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Initiation of Insulin therapy Often, insulin therapy is an
adjunct, when mono- or dual therapies do not achieve or maintain
desired glucose targets ( generally if a patients A1C is 8.5% on
dual oral therapy ). The guidelines note that higher A1C levels
often increase the likelihood of requiring the addition of basal
insulin to adequately achieve the necessary A1C reduction.
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Basal insulins offer simplicity in injection frequency and ease
of dose titration but may not be adequate to address postprandial
excursions. This is particularly true with further loss of islet
-cell function, whence a mealtime + basal regimen will be needed,
sometimes with mealtime insulin introduced meal by meal
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WHEN SHOULD INSULIN THERAPY BE STARTED? Diabetes Care Volume
37, June 2014
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Latent autoimmune diabetes in adults (LADA)
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The ADA/EASD guidelines reference certain situations in which
immediate initiation of insulin therapy is likely indicated : 1
specifically in patients who exhibit significant symptoms of
hyperglycemia 2 - in those who present with drastically elevated
plasma glucose levels (i.e., > 300350 mg/dl) or A1C (i.e.,
1012%).
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immediate initiation of insulin therapy : Some patients may
require immediate multiple daily insulin doses rather than a more
gradual progression in to insulin therapy.
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Initiation of Insulin therapy 3 - When catabolic features,
including : weight loss or ketonuria, are present, implementation
of insulin therapy is considered mandatory.
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Ketoacidosis can be present at the time of diagnosis of type 2
diabetes, especially in the presence of another metabolic stress (
i.e., myocardial infarction or infection or use of antiretroviral
therapy). In such situations, immediate use of insulin is
recommended and sometimes mandatory.
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Insulin is usually needed when diabetes is diagnosed in the
context of an acute medical event causing acute metabolic
deterioration, or in case of surgery or any other invasive
procedure, temporarily or for longer term.
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T2DM & Insulin Providers should avoid using insulin as a
threat or describing it as a failure or punishment. Basal insulin
alone is the most convenient initial insulin regimen, beginning at
10 U or 0.10.2 U/kg, depending on the degree of hyperglycemia.
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Basal Insulin & T2DM However, in patients with more severe
hyperglycemia (undefined by the guidelines), therapy can begin with
larger doses of 0.30.4 units/kg/day.
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Glargine & Detemir An advantage of both glargine and
detemir is that they have been shown to cause less nocturnal
hypoglycemia than NPH.
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Glargine & Detemir Comparatively, detemir is associated
with slightly less weight gain and a higher average unit
requirement when dosing. The main drawback to the long-acting
insulins is increased cost. ( Expensive )
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Titration Titration is described in the guidelines as the
addition of 12 units of basal insulin to the daily dose made once
or twice weekly for elevated fasting glucose readings. Or 5 10% of
the daily dose
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The ADA and EASD suggest : That elevations in postprandial
glucose may be a contributing factor to elevated A1C when fasting
glucose levels are at goal.
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The ADA and EASD Postprandial blood glucose excursions
contribute to the majority of elevation in A1C levels that are
close to goal. For A1C levels in the range of 7.38.4%, fasting and
postprandial glucose levels contribute equally to overall
glycemia.
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Bolus insulin therapy When basal insulin is not sufficient to
maintain glycemic control, bolus insulin therapy with short-acting
( human regular ) or rapid-acting ( aspart, lispro, and glulisine )
insulin just before meals is recommended.
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Bolus insulin therapy Rapid-acting insulins offer better
postprandial glucose control than regular human insulin, likely
because of their pharmacokinetic parameters. Nevertheless, cost
considerations still make regular human insulin a viable option in
cases in which cost containment is an issue and prandial insulin
therapy is required.
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When ?? Providers should be aware that when a patients daily
dose of basal insulin becomes > 0.5 units/kg/day, the need for
intensification with bolus insulin increases. When the total daily
dose of basal insulin nears 1 unit/kg/day, the addition of bolus
insulin is generally required to achieve glycemic control.
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First prandial insulin The guidelines suggest initiating
prandial insulin with a single dose just before the meal that
contains the largest carbohydrate content of the day. For most
patients, this is the evening meal.
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Prandial Insulin From there, a second and third injection may
be added before the other two meals if they require additional
coverage to limit glucose excursions.
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Premixed insulin However, some patients, such as those with a
history of nonadherence to their diabetes treatment regimen, may
not be appropriate candidates for basal - bolus therapy. In such
cases, premixed insulin products are available to increase
convenience but come with the drawback of reduced flexibility in
dosing.
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Premixed insulin Generally, such products are dosed twice
daily, before the morning and evening meals.
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AACE guidelines Current AACE guidelines recommend initiation of
insulin therapy for patients whose A1C level is > 9% and those
who have not achieved their glycemic targets with combination oral
therapy.
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However, the 2013 AACE algorithm and consensus statement offer
expanded recommendations, including a discussion on the initiation
of insulin in patients with an A1C as low as 7.5%, as an adjunct to
other therapies. Current opinion
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AACE advocates for tighter glycemic control, with a fasting
blood glucose target of 70110 mg/dl and a postprandial target of
< 140 mg/dl.
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AACE also favors long-acting basal insulin to target fasting
glucose as the initial insulin therapy in most situations, with
glargine or detemir preferred for the same reasons discussed
previously.
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AACE Basal Insulin : For those with an A1C > 8%, a higher
weight - based dose of 0.20.3 units/kg/day is recommended, as
opposed to the standard 0.10.2 units/kg/day.
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AACE Titration of Basal Insulin is based on fasting blood
glucose levels, - with 4 U added for FPG > 180 mg/dl, - 2 U
added of 140 < FPG < 180 mg/dl, and - 1 U added for 110 <
FPG < 139 mg/dl.
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The AACE guidelines recommend : Specific dosing instructions
for prandial insulin, initiating at 5 units before a meal,
representing ~ 7% of the basal insulin dose, although the
guidelines do not identify a specific meal.
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AACE The 2015 algorithm and consensus statement also support a
basal-bolus regimen for patients with symptomatic hyperglycemia and
an A1C level > 10%. Ideally, a full basal - bolus regimen is
preferred.
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AACE For patients with a total daily dose of 0.30.5
units/kg/day, 50% of that dose should constitute the prandial
insulin analog when initiated.
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AACE When a rapid-acting analog is used, the prandial dose
should be increased by 10% for postprandial glucose levels > 180
mg/dl.
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When adjusting the dose of premixed insulin, AACE recommends
that providers ; Consider predinner glucose levels for doses
administered before breakfast and fasting glucose levels for
adjustment of the predinner dose. The updated algorithm discusses a
specific increase of 10% of the total daily dose based on fasting
or premeal readings > 180 mg/dl.
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Insulin Preparations Current insulin preparations are generated
by recombinant DNA technology and consist of the amino acid
sequence of human insulin or variations thereof. In the United
States, most insulin is formulated as U-100 (100 units/mL).
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AIME Human insulin has been formulated with distinctive
pharmacokinetics or genetically modified to more closely mimic
physiologic insulin secretion. Insulins can be classified as : -
short-acting Or - long-acting
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Properties of Insulin Preparations NovoMix 30 Lansulin
70/30
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Aspart Insulin
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Insulin Lispro
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The rapid-acting insulin analogues should be injected 5 to 15
minutes before a meal. However, in infants or in older adults with
dementia who both have unpredictable eating patterns, rapid-acting
analogues can be administered after the meal without excessive
deterioration of glycemic control
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These insulin analogues are rapidly absorbed ( 30 minutes)
after subcutaneous injection, peak at 1 hour, and have a shorter
duration of action (3 to 4 hours) than regular insulin.
Furthermore, the intraindividual variability in time to maximum
serum insulin concentration is clinically significantly less for
rapid-acting insulin analogues than for regular human insulin
preparations