Intensive insulin therapy or flexible insulin therapy is a therapeutic regimen for
diabetes mellitus
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
treatment. This newer approach contrasts with
conventional insulin therapy. Rather than minimize the number of insulin injections per day (a technique which demands a rigid schedule for food and activities), the intensive approach favors flexible meal times with variable carbohydrate as well as flexible physical activities. The trade-off is the increase from 2 or 3 injections per day to 4 or more injections per day, which was considered "intensive" relative to the older approach. In North America in 2004, many endocrinologists prefer the term "flexible insulin therapy" (FIT) to "intensive therapy" and use it to refer to any method of replacing
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
that attempts to mimic the pattern of small continuous basal insulin secretion of a working pancreas combined with larger insulin secretions at mealtimes. The semantic distinction reflects changing treatment.
Rationale
Long-term studies like the
UK Prospective Diabetes Study (''UKPDS'') and the
Diabetes control and complications trial
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased a ...
(''DCCT'') showed that intensive insulin therapy achieved blood glucose levels closer to non-diabetic people and that this was associated with reduced frequency and severity of blood vessel damage. Damage to large and small blood vessels (
macro-
Macro (or MACRO) may refer to:
Science and technology
* Macroscopic, subjects visible to the eye
* Macro photography, a type of close-up photography
* Image macro, a picture with text superimposed
* Monopole, Astrophysics and Cosmic Ray Observ ...
and
microvascular disease
Microangiopathy (also known as microvascular disease, small vessel disease (SVD) or microvascular dysfunction) is a disease of the microvessels, small blood vessels in the microcirculation. It can be contrasted to coronary heart disease, an angio ...
) is central to the development of
complications of diabetes
Complications of diabetes mellitus include problems that develop rapidly (acute) or over time (chronic) and may affect many organ systems. The complications of diabetes can dramatically impair quality of life and cause long-lasting disability. Ove ...
.
This evidence convinced most physicians who specialize in diabetes care that an important goal of treatment is to make the biochemical profile of the diabetic patient (
blood lipids
Blood lipids (or blood fats) are lipids in the blood, either free or bound to other molecules. They are mostly transported in a protein capsule, and the density of the lipids and type of protein determines the fate of the particle and its influence ...
,
HbA1c
Glycated hemoglobin, also known as HbA1c, glycohemoglobin, hemoglobin A1c, A1C, is a form of hemoglobin (Hb) that is chemically linked to a sugar. Most monosaccharides, including glucose, galactose and fructose, spontaneously (i.e. non-enzymatic ...
, etc.) as close to the values of non-diabetic people as possible. This is especially true for young patients with many decades of life ahead.
General description
A working pancreas continually secretes small amounts of insulin into the blood to maintain normal glucose levels, which would otherwise rise from glucose release by the liver, especially during the early morning
dawn phenomenon
The dawn phenomenon, sometimes called the dawn effect, is an observed increase in blood sugar (glucose) levels that takes place in the early-morning, often between 2 a.m. and 8 a.m. First described by Schmidt in 1981 as an increase of blood glucose ...
. This insulin is referred to as ''basal insulin secretion'', and constitutes almost half the insulin produced by the normal pancreas.
Bolus insulin is produced during the digestion of meals. Insulin levels rise immediately as we begin to eat, remaining higher than the basal rate for 1 to 4 hours. This meal-associated (''prandial'') insulin production is roughly proportional to the amount of carbohydrate in the meal.
Intensive or flexible therapy involves supplying a continual supply of insulin to serve as the ''basal insulin'', supplying meal insulin in doses proportional to nutritional load of the meals, and supplying extra insulin when needed to correct high glucose levels. These three components of the insulin regimen are commonly referred to as basal insulin, bolus insulin, and high glucose correction insulin.
Two common regimens: pens, injection ports, and pumps
One method of intensive insulinotherapy is based on multiple daily injections (sometimes referred to in medical literature as ''MDI''). Meal insulin is supplied by injection of rapid-acting insulin before each meal in an amount proportional to the meal. Basal insulin is provided as a once or twice daily injection of dose of a long-acting insulin.
In an MDI regimen, long-acting insulins are preferred for basal use. An older insulin used for this purpose is ultralente, and beef ultralente in particular was considered for decades to be the gold standard of basal insulin. Long-acting
insulin analog
An insulin analog ( also called an insulin analogue) is any of several types of medical insulin that are altered forms of the hormone insulin, different from any occurring in nature, but still available to the human body for performing the same a ...
s such as
insulin glargine
Insulin glargine, sold under the brand name Lantus among others, is a long-acting modified form of medical insulin, used in the management of type I and type II diabetes. It is typically the recommended long acting insulin in the United King ...
(brand name ''Lantus'', made by
Sanofi-Aventis
Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...
) and
insulin detemir
Insulin detemir, sold under the brand name Levemir among others, is a long-acting modified form of medical insulin used to treat both type 1 and type 2 diabetes. It is used by injection under the skin. It is effective for up to 24 hours.
...
(brand name ''Levemir'', made by
Novo Nordisk
Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in nine countries, and affiliates or offices in five countries. Novo Nordisk is controlled by majority shareholder ...
) are also used, with insulin glargine used more than insulin detemir. Rapid-acting insulin analogs such as
lispro (brand name ''Humalog'', made by
Eli Lilly and Company
Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel ...
) and
aspart (brand name ''Novolog''/''Novorapid'', made by Novo Nordisk and ''Apidra'' made by Sanofi Aventis) are preferred by many clinicians over older regular insulin for meal coverage and high correction. Many people on MDI regimens carry
insulin pen
An injector pen (also called a medication pen) is a device used for injecting medication under the skin. First introduced in the 1980s, injector pens are designed to make injectable medication easier and more convenient to use, thus increasing ...
s to inject their rapid-acting insulins instead of traditional
syringe
A syringe is a simple reciprocating pump consisting of a plunger (though in modern syringes, it is actually a piston) that fits tightly within a cylindrical tube called a barrel. The plunger can be linearly pulled and pushed along the inside ...
s. Some people on an MDI regimen also use
injection port
An injection port is a medical device used for the administration of insulin or other physician approved medicine into the subcutaneous tissue (the tissue layer just below the skin). The device is similar to infusion sets used by insulin pumps, ex ...
s such as the
I-port to minimize the number of daily skin punctures.
The other method of intensive/flexible insulin therapy is an
insulin pump
An insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin therapy.
The device configuration may vary depending on design. A traditional pump ...
. It is a small mechanical device about the size of a deck of cards. It contains a syringe-like reservoir with about three days' insulin supply. This is connected by thin, disposable, plastic tubing to a needle-like
cannula
A cannula (; Latin meaning 'little reed'; plural or ) is a tube that can be inserted into the body, often for the delivery or removal of fluid or for the gathering of samples. In simple terms, a cannula can surround the inner or outer surfaces ...
inserted into the patient's skin and held in place by an adhesive patch. The infusion tubing and cannula must be removed and replaced every few days.
An insulin pump can be programmed to infuse a steady amount of rapid-acting insulin under the skin. This steady infusion is termed the basal rate and is designed to supply the background insulin needs. Each time the patient eats, he or she must press a button on the pump to deliver a specified dose of insulin to cover that meal. Extra insulin is also given the same way to correct a high glucose reading. Although current pumps can include a glucose sensor, they cannot automatically respond to meals or to rising or falling glucose levels.
Both MDI and pumping can achieve similarly excellent glycemic control. Some people prefer injections because they are less expensive than pumps and do not require the wearing of a continually attached device. However, the clinical literature is very clear that patients whose basal insulin requirements tend not to vary throughout the day or do not require dosage precision smaller than 0.5 IU, are much less likely to realize much significant advantage of pump therapy. Another perceived advantage of pumps is the freedom from syringes and injections, however, infusion sets still require less frequent injections to guide infusion sets into the subcutaneous tissue.
Intensive/flexible insulin therapy requires frequent blood glucose checking. To achieve the best balance of blood sugar with either intensive/flexible method, a patient must check his or her glucose level with a meter
monitoring of blood glucose several times a day. This allows optimization of the basal insulin and meal coverage as well as correction of high glucose episodes.
Advantages and disadvantages
The two primary advantages of intensive/flexible therapy over more traditional two or three injection regimens are:
# greater flexibility of meal times, carbohydrate quantities, and physical activities, and
# better glycemic control to reduce the incidence and severity of the complications of diabetes.
Major disadvantages of intensive/flexible therapy are that it requires greater amounts of education and effort to achieve the goals, and it increases the daily cost for glucose monitoring four or more times a day. This cost can substantially increase when the therapy is implemented with an insulin pump and/or continuous glucose monitor.
It is a common notion that more frequent hypoglycemia is a disadvantage of intensive/flexible regimens. The frequency of hypoglycemia increases with increasing effort to achieve normal blood glucoses with most insulin regimens, but hypoglycemia can be minimized with appropriate glucose targets and control strategies. The difficulties lie in remembering to test, estimating meal size, taking the meal bolus and eating within the prescribed time, and being aware of snacks and meals that are not the expected size. When implemented correctly, flexible regimens offer greater ability to achieve good glycemic control with easier accommodation to variations of eating and physical activity.
A 2020
Cochrane Cochrane may refer to:
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*Cochrane railway station, Sydney, a railway station on the closed Ropes Creek railway line
Canada
* Cochrane, Alberta
* Cochrane Lake, Alberta
* Cochrane District, Ontario
** Cochrane, Ontario, a town wit ...
systematic review
A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
did not find enough evidence of reduction of cardiovascular mortality, non-fatal
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
or non-fatal
stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
when comparing insulin to metformin monotherapy.
Semantics of changing care: why "flexible" is replacing "intensive" therapy
Over the last two decades, the evidence that better glycemic control (i.e., keeping blood glucose and HbA1c levels as close to normal as possible) reduces the rates of many complications of diabetes has become overwhelming. As a result, diabetes specialists have expended increasing effort to help most people with diabetes achieve blood glucose levels as close to normal as achievable. It takes about the same amount of effort to achieve good glycemic control with a traditional two or three injection regimen as it does with flexible therapy: frequent glucose monitoring, attention to timing and amounts of meals. Many diabetes specialists no longer think of flexible insulin therapy as "intensive" or "special" treatment for a select group of patients but simply as standard care for most patients with
type 1 diabetes
Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...
.
Treatment devices used
The
insulin pump
An insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin therapy.
The device configuration may vary depending on design. A traditional pump ...
is one device used in intensive insulinotherapy. The insulin pump is about the size of a beeper. It can be programmed to send a steady stream of insulin as ''basal insulin''. It contains a reservoir or cartridge holding several days' worth of insulin, the tiny battery-operated pump, and the computer chip that regulates how much insulin is pumped. The infusion set is a thin plastic tube with a fine needle at the end. There are also newer "pods" which do not require tubing. It carries the insulin from the pump to the infusion site beneath the skin. It sends a larger amount before eating meals as "bolus" doses.
The insulin pump replaces insulin injections. This device is useful for people who regularly forget to inject themselves or for people who don't like injections. This machine does the injecting by replacing the slow-acting insulin for basal needs with an ongoing infusion of rapid-acting insulin.
Basal insulin: the insulin that controls blood glucose levels between meals and overnight. It controls glucose in the fasting state.
Boluses: the insulin that is released when food is eaten or to correct a high reading.
Another device used in intensive insulinotherapy is the
injection port
An injection port is a medical device used for the administration of insulin or other physician approved medicine into the subcutaneous tissue (the tissue layer just below the skin). The device is similar to infusion sets used by insulin pumps, ex ...
. An injection port is a small disposable device, similar to the infusion set used with an insulin pump, configured to accept a syringe. Standard insulin injections are administered through the injection port. When using an injection port, the syringe needle always stays above the surface of the skin, thus reducing the number of skin punctures associated with intensive insulinotheraphy.
References
{{DEFAULTSORT:Intensive Insulinotherapy
Insulin therapies
pl:Insulinoterapia