Insulin is a hormone produced by the beta-cells of the pancreas. It is
a protein with a molecular weight of approximately 5700 kDa. It is formed
from proinsulin after cleavage into insulin and C-peptide (Fig 1).
The normal insulin secretion is 0.5-0.7 units/kg per day.
Fig 1: Insulin has two chains A and B and during its production. A third
chain of peptides called C Peptide links these. C peptide is removed before
Insulin is secreted into the blood.
Functions of Insulin
entry of glucose into cells for utilization as energy source.
entry of amino acids into cells, enhancing protein synthesis
fat storage and prevents mobilization of fat for energy (lipolysis)
storage of glucose as glycogen in muscle and liver cells (glycogenesis)
formation of glucose from non carbohydrates (gluconeogenesis)
for Insulin Therapy
- All individuals
with Type 1 diabetes
2 diabetes not adequately controlled by other forms of therapy (drugs,
diet and exercise)
related diabetes mellitus
with Type 2 diabetes during periods of physiological stress (major surgery,
hyperglycemic nonketotic syndrome (HHNS)
with tuberculosis often do better with insulin.
diabetes (pancreatitis, corticosteroids)
Secretion and Functions of Insulin
The body's homeostatic system maintains a uniform blood glucose level
between meal times and fasting periods. Basal insulin secretion maintains
a balance against high blood sugar during the resting state.
The insulins available for routine clinical use are derived from three
sources beef, pork and human (recombinant).
The insulins available now are the "pure" varieties and
contain negligible risks of immunogenicity. These are of four types
- beef, porcine, mixed and human insulin
insulin differs from human insulin in three amino acids, namely
A8, A 10 and B 30.
insulin differs from human insulin in only one amino acid i.e. B30
position. Thus, porcine insulin is less immunogenic than beef insulin.
insulin contains a mixture of bovine and porcine insulin and it
is more antigenic than single species
insulin is pure and has the same amino acid structure as that of
native insulin. They are made by genetic engineering or by transformation
from porcine insulin by substituting alanine with threonine in the
and Types of Insulin
In a normal person without diabetes, insulin is secreted throughout the
day and thus there is a basal level and peaks of insulin secretion are
seen following meals when the blood glucose rises (Fig 2).
Fig 2: Physiological
Secretion of Insulin.
The insulins available for clinical use can be classified according to
peak effect and duration of action
Fig 3: Peak
and Duration of Action of Rapid Acting Insulins
Rapid acting Insulins: The
only insulin analog available in India is the rapid acting Lispro. It
reaches the blood within 15 minutes after injection. It peaks 30 to 90
minutes later and may last as long as 4-5 hours (Fig 3). It is injected
just before meals.
Fig 4: Peak
and Duration of Action of Short Acting Insulins
acting (Regular): Short-acting (regular) insulin usually
reaches the blood within 30 minutes after injection. It peaks 2 to 4 hours
later and stays in the blood for about 4 to 8 hours (Fig.4).
Fig 5: Peak and Duration of Action of Intermediate Acting Insulins
acting: NPH and Lente (Fig.5): Intermediate-acting (NPH
and lente) insulins reach the blood 2 to 6 hours after injection. They
peak 4 to 14 hours later and stay in the blood for about 14 to 20 hours.
Intermediate-acting insulins include lente and NPH. Insulin preparations
with a predetermined proportion of NPH mixed with regular, such as 70%
NPH to 30% regular, or a 50/50 mix are called intermediate acting insulin.
Fig 6: Peak
and Duration of Action of Long Acting Insulins
Long Acting: Ultralente
(Fig.6): Long-acting (ultralente) insulin takes 6 to 14 hours to start
working. It has no peak or a very small peak 10 to 16 hours after injection.
It stays in the blood between 20 and 24 hours.
Fig 7: Peak
and Duration of Action of Very Long Acting Insulins
long acting: Lantus (Fig.7): Lantus is newer insulin,
which works for 24 hrs. The chemical structure of Lantus makes it to be
released steadily and continuously in the body, mimicking almost the basal
physiological secretion of Insulin. It is the only long acting insulin
which is clear and cannot be mixed up with any other insulin.
Lispro and Aspart are only clear insulins or solution of insulin. Regular
insulin modified with addition of protamine and zinc (NPH) or zinc alone
(Lente, Ultralente) to prolong duration of action of insulin are cloudy
Lispro is an insulin analog identical to human insulin except for the
reversal of two amino acids, lysine and proline, on the B chain.
Administration and Storage
Insulin vials should be preferably stored at 4-80C. If possible they should
be kept in the refrigerator, but not in the freezer compartment. The insulin
vial should be brought down to body temperature by gently rubbing it between
the palms before withdrawing the insulin into the syringes.
If refrigeration facilities are unavailable, then the currently used vial
can be stored at room temperature away from heat and direct sunlight.
If vials have to be stored for longer periods, a simple method is for
the unopened vials to be stored in the earthen pots, which contain drinking
water and are found in most homes where a refrigerator is not present.
There are no precise formulae by which the initial dose can be calculated.
The usual total dose of insulin is between 0.5 and 1 unit/kg/day although
it is usual to start with a starting dose of 0.25 unit/kg/day.
The usual regimen is to start with a small dose of an intermediate acting
insulin about 8-12 units S.C. before breakfast or with a mixture of a
short acting insulin and Intermediate acting insulin in small doses.
When stabilized most patients require about 60% of total insulin in the
morning and 40% in the evening. However insulin-dosing regimen is highly
individualized and it has to be tailor made depending upon the patient’s
age, weight, sugar levels and presence of any other condition, which may
affect the status of blood sugars.
Often overweight patients may need more insulin due to insulin resistance.
of the short acting and the intermediate/long acting insulins available
here may be mixed in the same syringe except Lantus.
are presently available in strengths of U-40, and U-100. The patient
must ensure that the syringes used by him/her are compatible with
the strength of insulin used.
The various methods of insulin delivery are by injections, insulin pens,
and insulin pumps and lately by inhalation (EXUBERA). The inhaled insulin
is in the last phase of clinical trial in USA and is expected to be available
in the market by next year.
1) Injection. The needle and syringe is the commonest
of the four insulin delivery systems. Today's needles are much improved
from years ago. They are sharper, finer, and coated with Teflon to make
injections much less painful than they used to be.
Injections should be given preferably 20-30 minutes before the meal to
achieve proper peak of insulin action corresponding to elevated sugar
levels after a meal except Lantus which can be given just before the meals.
The needle is to be inserted in the pinched up skin at 90o angle so that
the injection is in the subcutaneous tissue. It is advisable to use disposable
syringes, which are now easily available.
The cost of the syringe is often a limiting factor to the routine use
of these syringes. Patients can reuse the same disposable syringe and
decrease the costs. Insulin syringes may be reused 2-3 times if the needle
is not blunt. The same syringe can be used for different sites but it
should never be used on different patients.
pens. An insulin pen is a compact, portable device that serves
exactly the same function as a needle and syringe, but is handier and
more convenient to use. A wide variety of disposable and reusable insulin
pens that come pre-loaded with their insulins are available in the market.
One of the great advantages of insulin pens is that they are more suitable
for patients who are frequent travelers.
Insulin pump. An insulin pump is a computer-controlled device,
which comes in the size and shape of a pager. It painlessly and accurately
delivers insulin all day long through a tiny tube inserted just under
Insulin pump is the best and most intensive way that currently exists
to control diabetes. The pump is not entirely pain-free. The location
of the infusion set has to be changed after every second or third day
to prevent infection at the site.
Insulin Therapy Regimens
To optimize glycemic control, an individual would need to receive small
amounts of insulin continuously (basal), with boluses of insulin before
meals and snacks. Adjust the dose based on self-monitoring of glucose
levels, HbA1C, weight, lifestyle and other concurrent conditions.
Therapy for Type 1 diabetes
Successful insulin therapy for type 1 diabetes requires the co-ordination
of the following factors:
2 main insulin regimens
injections of mixed intermediate (cloudy isophane) or long-acting
insulin with a short acting (clear soluble) insulin.
basal bolus regimen: This is particularly suitable for patients with
irregular meal times or hectic lifestyles. This consists of intermediate
acting insulin at bedtime (to provide the basal insulin requirement)
with short acting insulin before each meal.
Dose Insulin (MDI) regimen: Here a combination of short and long acting
insulin (Mixtard 30:70 0r 50:50) is given prior to breakfast and dinner,
while a short acting insulin is given at lunch. This regime can be
modified in numerous ways to suit the patient’s needs, e.g.
long acting insulin may be added at bedtime.
Nowadays an entirely new dimension has been added with the availability
of ultra short acting Lispro/Aspart insulin and the very long acting
Glargine (Lantus) insulins. Glargine insulin is given at bedtime,
with the ultra short insulins being administered prior to each major
of blood glucose (SMBG) with or with a glucometer is recommended at least
once daily. Testing time should be changed frequently with the majority
of the readings being pre-meal or at bedtime.
therapy for Type 2 diabetes
Insulin therapy for type 2 diabetes can be supplementary or absolute depending
upon the indication.
Intermediate acting isophane insulin works well on its own in these patients
but a soluble component is often needed to achieve good glycemic control.
Soluble insulin can be added if postprandial hyperglycemia 2 hours after
a meal is excessive (> 180 mg/dl).
A few elderly patients can be managed on once daily lente insulin. Lente
insulin is regular insulin complexed with zinc to form a long acting suspension
and cannot be mixed with soluble insulin.
When mixing of two different types of insulin is required in a single
syringe then mutual contamination of the two vials must be avoided. What
is equally important is that you must always load the rapid acting insulin
first and then the intermediate or long acting insulin. If you do the
reverse then you are likely to change the time action profile of the short
or rapid acting insulin. Once the injection is prepared inject immediately
and definitely not after 5 minutes.
of insulin injection
The sites where the injections can be given are shown in Fig 8. These
include the abdomen, outer upper arms, the thighs, the buttocks, and hip
areas. Do not inject insulin in bony areas or near any of your joints.
Efforts must be made to rotate the site of the injection throughout the
permissible areas and not inject only into one region.
Fig 8: Sites of insulin Injections
of Insulin Therapy
(Low blood sugar): This is a major side effect and
the patient should be educated about it before initiation of insulin
and he should be taught about the emergency measures to be taken in
such a condition.
The impurities present in the older insulins gave
rise to antibodies, which interfere with normal insulin action. However,
newer insulins are purer and the chances of insulin resistance minimal.
Insulin has salt retaining properties and may cause
fluid retention in some patients.
(Abnormal fat accumulation): This may present as lipoatrophy
(decreased fat) or lipohypertrophy (increased fat). Lipoatrophy was
seen with the use of older insulins and it is rare with the newer
insulins. Lipohypertrophy can be seen with the use of any insulin.
The best way to avoid this condition is to frequently change the site
or systemic hypersensitivity reactions
Never be in haste. Always start with a low dose, go slow. There is no
rush to achieve adequate control since this may take several weeks. Start
with 8-10 units twice daily. Increase by 2-4 units every 2-3 days according
to capillary blood glucose values and your physical condition.
always consult your physician about any healthcare questions you may have,
especially before trying a new medication, diet, fitness program, or approach
to health care issues.
Last updated on 13-12-2002