Type 1 Diabetes Mellitus:

Treatment
RP
 Introduction
Because the complications of DM are
related to glycemic control, normoglycemia or
near normoglycemia is the desired, but often
elusive, goal for most patients.
However, normalization of the plasma glucose
for long periods of time is extremely
difficult.
Improvement in glycemic control will lower
the risk of diabetes complications
 Factors that influenced the glycemic control
are :
Patient's age,
Ability to understand and implement a complex
treatment regimen,
Presence and severity of complications of diabetes,
Ability to recognize hypoglycemic symptoms,
Presence of other medical conditions or treatments
that might alter the response to therapy,
Lifestyle and occupation (e.g., possible consequences
of experiencing hypoglycemia on the job),
Level of support available from family and friends
 The Goal
The glycemic control goal is to achive an A1C
as close to normal as possible (<7.0%) without
significant hypoglycemia.
 Type 1 DM Treatment
The goal of type 1 DM treatment is to design
and implement insulin regimens that mimic
physiologic insulin secretion.
Insulin replacement for meals should be
appropriate for the carbohydrate intake
and promote normal glucose utilization and
storage.
 Insulin Management
To achieved euglycemia or near normal
glycemia its requires multiple resources including
:
Thorough and continuing patient education,
Comprehensive recording of plasma glucose
measurements and nutrition intake by the patient,
A variable insulin regimen that matches glucose intake
and insulin dose.
Insulin regimens usually include :
Multiple-component insulin regimens,
Multiple daily injections (MDI),
Or insulin infusion devices (each discussed below).
 Insulin Management
The benefits of intensive diabetes
management and improved glycemic control
include a reduction in the microvascular
complications of DM and a reduction in the
macrovascular complications of DM.
Intensive diabetes management in pregnancy
reduces the risk of fetal malformations and
morbidity.
 Insulin Preparation
Current insulin preparations are generated
by recombinant DNA technology and consist
of the amino acid sequence of human insulin
or variations that mimic physiologic insulin
secretion.
Insulin can be classified as short acting or
long acting.
 Insulin Preparation
One short-acting insulin formulation, insulin
lispro, is an insulin analogue in which the
28th and 29th amino acids (lysine and proline)
on the insulin B chain have been reversed by
recombinant DNA technology.
 Insulin Preparation
Insulin aspart and insulin glulisine are
other genetically modified insulin analogues
with properties similar to lispro for prandial
coverage.
These insulin analogues have full biologic
activity but less tendency for self aggregation,
resulting in more rapid absorption and onset
of action and a shorter duration of action.
 Insulin Preparation
Insulin glargine is a long-acting biosynthetic
human insulin that differs from normal insulin
in that asparagine is replaced by glycine at
amino acid 21, and two arginine residues are
added to the C-terminus of the B chain.
 Insulin Preparation
The onset of insulin glargine action is later, the
duration of action is longer (~24 h), and there
is no pronounced peak.
 Insulin Preparation
Insulin detemir has a fatty acid side chain
that prolongs its action by slowing absorption
and catabolism.
 Insulin Preparation
Basal insulin requirements are provided by
long-acting (NPH insulin, insulin glargine, or
insulin detemir) insulin formulations.
These are usually prescribed with short-acting
insulin in an attempt to mimic physiologic
insulin release with meals.
The aim of this mixing is to make the patient
more convenient (only two injection/day)
However, the following guidelines should be
followed:
 Insulin Preparation
1. Mix the different insulin formulations in the syringe
immediately before injection (inject within 2 min after
mixing);
2. Do not store insulin as a mixture;
3. Follow the same routine in terms of insulin mixing
and administration to standardize the physiologic
response to injected insulin; and
4. Do not mix insulin glargine or detemir with other
insulins.
The miscibility of human regular and NPH
insulin allows for the production of combination
insulins that contain 70% NPH and 30% regular
(70/30), or equal mixtures of NPH and regular
(50/50).
 Insulin Preparation
Other combination insulin formulations are
insulin aspart (70/30) and insulin lispro (75/25
and 50/50).
 Insulin Preparation
Insulin can also be delivered by inhalation
by using a powder formulation of regular
insulin and a delivery device( inhaled regular
insulin), but contraindicated with
smokers.
Inhaled insulin has no physiologic advantage
over injected short-acting insulin but may be
considered in selected patients with type 2
DM who are unwilling to use injected
insulin.
 Insulin Regimens
In all regimens, long-acting insulins (NPH,
glargine, or detemir) supply basal insulin,
whereas regular, insulin aspart, glulisine, or
lispro insulin provides prandial insulin.
Short-acting insulin analogues should be
injected just before (<20 min) or just after a
meal; regular insulin is given 3045 min prior
to a meal but, no insulin regimen reproduces
the precise insulin secretory pattern of the
pancreatic islet.
 Insulin Regimens
To determine the meal component of the
preprandial insulin dose, the patient uses an
insulin : carbohydrate ratio (a common ratio is
11.5 units/10 g of carbohydrate, but this must
be determined for each individual).
To this insulin dose is added the supplemental or
correcting insulin based on the preprandial blood
glucose [one formula uses 1 unit of insulin for
every 2.7 mmol/L (50 mg/dL) over the
preprandial glucose target; another formula uses
(body weight in kg) x (blood glucose desired
glucose in mg/dL)/1500].
 Insulin Regimens
One commonly used regimen consists of twice-
daily injections of a long-acting insulin like NPH
(detemir could be used instead) mixed with a
short-acting insulin before the morning and
evening meal.
Such regimens usually prescribe two-thirds of
the total daily insulin dose in the morning (with
about two-thirds given as long-acting insulin and
one-third as short-acting) and one-third before
the evening meal (with approximately one-half
given as long-acting insulin and one-half as short-
acting).
 Insulin Regimens
Continuous subcutaneous insulin infusion (CSII) is a
very effective insulin regimen for the patient with
type 1 diabetes.
To the basal insulin infusion, a preprandial insulin
("bolus") is delivered by the insulin infusion device
based on instructions from the patient, who uses an
individualized algorithm incorporating the preprandial
plasma glucose and anticipated carbohydrate
intake.
These devices require a health professional with
considerable experience with insulin infusion devices
and very frequent patient interactions with the
diabetes management team.
 Other Agents That Improve Glucose
Control
Amylin is an analogue (pramlintide) was
created and found to reduce postprandial
glycemic excursions in type 1 and type 2
diabetic patients taking insulin.
Addition of pramlintide produces a
modest reduction in the A1C and seems
to dampen meal-related glucose excursions.
 Other Agents That Improve Glucose
Control
In type 1 diabetes, pramlintide is started as a
15-g SC injection before each meal and
titrated up to a maximum of 3060 g as
tolerated.
In type 2 DM, pramlintide is started as a 60-g
SC injection before each meal and may be
titrated up to a maximum of 120 g.
 Other Agents That Improve Glucose
Control
The major side effects are nausea and
vomiting, and dose escalations should be slow
to limit these side effects.
 Other Agents That Improve Glucose
Control
Because pramlintide slows gastric emptying, it
may influence absorption of other
medications and should not be used in
combination with other drugs that slow GI
motility.