Intensive insulinotherapy (patient information)

Overview
Intensive insulinotherapy or flexible insulin therapy is a therapeutic regimen for diabetes mellitus treatment. In North America in 2004, many endocrinologists prefer the term "flexible insulin therapy" to intensive therapy and use it to refer to any method of replacing insulin that attempts to mimic the pattern of insulin secretion of a working pancreas. See at end of article for how semantic distinctions reflect changing treatment.

Rationale for intensive or flexible treatment
Long-term studies like the UK Prospective Diabetes Study (UKPDS) and the Diabetes control and complications trial (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 damage) 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.

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 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. Levemir, made by Novo Nordisk, is another long-acting insulin in trials. Also insulin glargine (brandname: Lantus, made by Aventis) is used. Rapid-acting insulin analogs such as lispro (brandname: Humalog, made by Eli Lilly and Company) and aspart (brandname: Novolog/Novorapid, made by Novo) are preferred over older regular insulin for meal coverage and high correction. Many people on MDI regimens carry insulin pens to inject their rapid-acting insulins instead of traditional syringes.

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. Current pumps do not include a glucose sensor and 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. A primary advantage of pumps is the freedom from syringes and injections.

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 of intensive/flexible insulin therapy
For most people with diabetes, the two primary advantages of intensive/flexible therapy over more traditional two or three injection regimens are greater flexibility of timing and amounts of meals and better glycemic control.

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 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.

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.

Acknowledgements
The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.