Intensive insulinotherapy
Encyclopedia
Intensive insulinotherapy is a therapeutic regimen for diabetes mellitus
treatment. This newer approach contrasts with conventional insulinotherapy
. 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
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.
(DCCT) showed that intensive insulinotherapy 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-
and microvascular disease
) is central to the development of complications of diabetes mellitus.
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
, HbA1c
, 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.
Most insulin used each day 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, meal insulin, and high correction.
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. Insulin glargine
(brandname: Lantus, made by Sanofi-Aventis
) is used. Also, Levemir, made by Novo Nordisk
, is another long-acting insulin that is used to a lesser extent. Rapid-acting insulin analog
s such as lispro (brandname: Humalog, made by Eli Lilly and Company
) and aspart (brandname: 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
s to inject their rapid-acting insulins instead of traditional syringe
s. Some people on an MDI regimen also use injection port
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
. 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
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, and 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.
Major disadvantages of intensive/flexible therapy are that it requires greater amounts of education and effort to achieve the goals, and it substantially increases the daily cost of diabetes care.
It is a common misconception 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 any insulin regimen. When traditional regimens are used aggressively enough to achieve near-normal glycosylated hemoglobin A1c
levels, hypoglycemia is at least as frequent as with flexible regimens. When used correctly, flexible regimens offer greater ability to achieve good glycemic control with easier accommodation to variations of eating and physical activity.
.
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 on-going 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 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.
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
treatment. This newer approach contrasts with conventional insulinotherapy
Conventional insulinotherapy
Conventional insulinotherapy is a therapeutic regimen for treatment of diabetes mellitus which contrasts with the newer intensive insulinotherapy....
. 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
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
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 for intensive or flexible treatment
Long-term studies like the UK Prospective Diabetes Study (UKPDS) and the Diabetes control and complications trialDiabetes control and complications trial
The Diabetes Control and Complications Trial , was a landmark medical study conducted by the United States National Institute of Diabetes and Digestive and Kidney Diseases . It significantly changed the management principles of Diabetes mellitus from the 1990s onwards...
(DCCT) showed that intensive insulinotherapy 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-
Macroangiopathy
-Pathophysiology:In macroangiopathy, fat and blood clots build up in the large blood vessels, stick to the vessel walls, and block the flow of blood....
and microvascular disease
Microvascular disease
Microangiopathy is an angiopathy affecting small blood vessels in the body. It can be contrasted to macroangiopathy....
) is central to the development of complications of diabetes mellitus.
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
Blood lipids 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 on metabolism. The concentration of blood lipids depends on...
, HbA1c
Glycosylated hemoglobin
Glycated hemoglobin is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. It is formed in a non-enzymatic glycation pathway by hemoglobin's exposure to plasma glucose...
, 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.
A general description of intensive or flexible therapy
A working pancreas continually secretes small amounts of insulin into the blood to prevent the body from shifting into "starvation metabolism." This insulin is referred to as basal insulin secretion.Most insulin used each day 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, meal insulin, and high correction.
Two common intensive/flexible 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. Insulin glargine
Insulin glargine
Insulin glargine, marketed by Sanofi-Aventis under the name Lantus, is a long-acting basal insulin analogue, given once daily to help control the blood sugar level of those with diabetes. It consists of microcrystals that slowly release insulin, giving a long duration of action of 18 to 26 hours,...
(brandname: Lantus, made by Sanofi-Aventis
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
) is used. Also, Levemir, made by Novo Nordisk
Novo Nordisk
Novo Nordisk manufactures and markets pharmaceutical products and services. Created in 1989 through a merger of two Danish companies dating back to the 1920s, it has become one of the world's leading companies in diabetes care, where Novo Nordisk pursues research into pulmonary delivery systems;...
, is another long-acting insulin that is used to a lesser extent. Rapid-acting insulin analog
Insulin analog
An insulin analog is an altered form of insulin, different from any occurring in nature, but still available to the human body for performing the same action as human insulin in terms of glycemic control...
s such as lispro (brandname: Humalog, made by Eli Lilly and Company
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
) and aspart (brandname: 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
Insulin pen
An insulin pen is used to inject insulin for the treatment of diabetes. It is composed of an insulin cartridge and a dial to measure the dose, and is used with disposable Pen needles to deliver the dose.-Types of pens:...
s to inject their rapid-acting insulins instead of traditional syringe
Syringe
A syringe is a simple pump consisting of a plunger that fits tightly in a tube. The plunger can be pulled and pushed along inside a cylindrical tube , allowing the syringe to take in and expel a liquid or gas through an orifice at the open end of the tube...
s. Some people on an MDI regimen also use injection port
Injection port
An injection port is a medical device used for the administration of insulin or other physician approved medicine into the subcutaneous tissue...
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
Insulin pump
The insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin infusion therapy.The device includes:...
. 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
Cannula
A cannula or canula is a tube that can be inserted into the body, often for the delivery or removal of fluid or for the gathering of data...
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, and 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
Blood glucose monitoring
Blood glucose monitoring is a way of testing the concentration of glucose in the blood . Particularly important in the care of diabetes mellitus, a blood glucose test is performed by piercing the skin to draw blood, then applying the blood to a chemically active disposable 'test-strip'...
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 of intensive/flexible insulin therapy
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 substantially increases the daily cost of diabetes care.
It is a common misconception 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 any insulin regimen. When traditional regimens are used aggressively enough to achieve near-normal glycosylated hemoglobin A1c
Glycosylated hemoglobin
Glycated hemoglobin is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. It is formed in a non-enzymatic glycation pathway by hemoglobin's exposure to plasma glucose...
levels, hypoglycemia is at least as frequent as with flexible regimens. When used correctly, flexible regimens offer greater ability to achieve good glycemic control with easier accommodation to variations of eating and physical activity.
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 diabetesDiabetes mellitus type 1
Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose...
.
Treatment device used in intensive insulinotherapy
The insulin pumpInsulin pump
The insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin infusion therapy.The device includes:...
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 on-going 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
Injection port
An injection port is a medical device used for the administration of insulin or other physician approved medicine into the subcutaneous tissue...
. 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.