WHAT IS INSULIN AND HOW IS IT USED TO TREAT DIABETES?

General Guidelines for Treating Type 1 Diabetes

Insulin is essential for survival and is the mainstay treatment for type 1 diabetics. Major studies have now provided substantial evidence that intensive treatment with insulin and tight control of blood glucose levels significantly delay the major complications specific to diabetes and may even have benefits for the heart. Intensive insulin treatment in early diabetes may also help preserve any residual insulin secretion for at least two years.

There are, however, some significant complications from intensive insulin therapy:

A diet plan that compensates for insulin administration and supplies healthy foods is extremely important. [For detailed information, see the Well-Connected Report #42, Diabetes Diet .] Pancreas transplantation eventually may be recommended for patients who cannot control glucose levels without frequent episodes of severe hypoglycemia.

Regimens for Intensive Insulin Treatment

The goal of intensive therapy is to keep blood glucose levels as close to normal as possible. [ See Table Glucose Goals for Patients with Diabetes.] In one major study, even when levels were 40% higher than non-diabetic levels, benefits were still observed.

Standard insulin therapy is usually one or two insulin injections, one daily blood sugar test, and visits to the health care team every three months. For strictly controlling blood glucose, however, intensive management is required. The regimen is complicated although newer insulin forms are reporting ease of use with better control. Recent approaches for insulin administration attempt to mimic nature.

There are two components to flexible insulin administration and number of variations of insulin delivery for accomplishing them :

Because of the higher risk for hypoglycemia in children, experts recommend that intensive treatment be used very cautiously in children under 13 and not at all in very young children.

Insulin Forms

Insulin cannot be taken orally because the body's digestive juices destroy it. Injections of insulin under the skin ensure that it is absorbed slowly by the body for a long-lasting effect. The timing and frequency of insulin injections depend upon a number of factors:

Regular Insulin. Regular insulin (R) begins to act 30 minutes after injection, reaches its peak at two to four hours and lasts about six to eight hours or longer after that.

Intermediate-Acting Insulin. NPH (neutral protamine Hagedorn) insulin has been the standard intermediate-acting form. It works within one to two hours, peaks at four to 10 hours, and lasts up to 16 hours. Lente (insulin zinc) is another intermediate-acting insulin that peaks between four to 12 hours and up to 18 hours.

Long Acting Insulin. Long-acting insulins are released slowly and can last up to 24 hours. Insulin glargine (Lantus) is a very promising agent. It matches parts of natural insulin and maintains stable activity for more than 24 hours. Studies are suggesting that it pose less of a risk for hypoglycemia and weight gain than NPH. It has a higher incidence of pain at the injection site than NPH. Other basal insulin forms (detemir) are also being investigated. Ultralente insulin peaks at 10 hours and lasts up to 20 hours but varies greatly in activity from day to day.

Rapidly Acting Insulin. Insulin lispro (Humalog) and insulin aspart (Novo Rapid) lower blood sugar very quickly and are short-acting (lasting about four hours). Optimal timing for administering it is about fifteen minutes before a meal. Their short action reduces the risk for hypoglycemic events afterward. In one study, patients experienced fewer hypoglycemic episodes, particularly at night, than those on standard insulin. Lispro has no effect on glycated hemoglobin levels, however. There is some concern that short-acting forms may cause birth defects if pregnant women take them.

Combinations. Regimens generally include combinations of short and longer-acting insulins to help match the natural cycle. Several preparations that combine insulins are available. .

Alternative Methods for Delivering Insulin

Insulin Pumps. Patients who use insulin pumps tend to have better blood glucose control and quality of life and fewer hypoglycemic episodes than those who rely on separate injections. Some pumps are worn externally and are programmed to deliver insulin through a catheter in the skin or the abdomen. The device is about the size of a pack of cards and has a digital display. They are more expensive than insulin shots, however, and have complications, such as blockage in the device. Some people have had difficulty getting rid of air bubbles in pump cartridges as they fill them up. New pumps are available that use prefilled cartridges (D-Tron) and thus help reduce the air bubble problem. Some experts are concerned that using short-acting insulins for continuous delivery with the pump may increase the risk for ketoacidosis, because if delivery of the insulin is interrupted for some reason, such as blockage, there is no insulin reserve to control blood sugar levels. At this time, the pumps are best suited for adults and adolescents, but they may also be effective for children.

Insulin Pens. Insulin pens, which contain cartridges of insulin, have been available for some time. Until recently, they were fairly complicated and difficult to use. Newer prefilled pens (Humulin Pen, Humalog) are disposable and allow the patient to dial in the correct amount.

Inhaled Aerosol. Investigative oral insulin forms are receiving a lot of attention as a possible replacement for insulin shots. Some are inhaled (Eubera) or administered using a spray that is absorbed in the cheek lining (Oralin). Oral administration may help reduce heart complications compared to injections, although a study on mice reported possible liver problems and increased triglyceride levels. More research is needed. Inhalants probably cannot completely replace injections altogether, in any case. Instead, they might be useful for specific situations, such as for people with type 2 diabetes, in emergency situations when a rapid insulin boost is needed, or for children who are at high risk for developing type 1 diabetes.

Other Alternative Insulin Delivery Methods. Another promising avenue of investigation for delivering insulin is the use of ultrasound pulses.

Supplementary Agents Used to Prevent Postprandial Hyperglycemia

In addition to rapidly acting insulin, other agents are being investigated for control of postprandial hyperglycemia, the sudden increase in blood sugar after a meal. Postprandial hyperglycemia is now believed to be a significant long-term threat to the body.

Alpha-Glucosidase Inhibitor s. Alpha-glucosidase inhibitors (acarbose and miglitol) slow intestinal absorption of carbohydrates. Acarbose tends to lower insulin levels after meals, a particular advantage, since higher levels of insulin after meals are associated with an increased risk for heart disease.

Pramlintide. Pramlintide (Symlin), known as an amylin analog, is derived from a natural hormone that acts in concert with the body's insulin in the pancreas to control hyperglycemia. It slows stomach emptying and delays absorption of nutrients in the intestine. Some studies indicate that it helps control glucose levels without increasing the risk for hypoglycemia or increasing weight when added to insulin regimens. It is being considered for approval for both type 1 and type 2 insulin-dependent diabetes.